Liver Aspartate Aminotransferase Research Articles

Nutritional and safety assessment of aqueous extract of nutmeg seeds, Myristica fragrans

Nutmeg, Myristica fragrans is used as a spice or medicinal plant to manage ailments. This study evaluated the nutritional and safety assessment of an aqueous extract of Myristica fragrans in Wistar rats. Thirty male Wistar rats weighing 180 - 240 g were randomly distributed into five groups: Control received distilled water, while 100, 200, 300, and 400 mg/kg body weight represented the treatment groups, respectively. The extract was orally administered to the animals for 28 days and then euthanized under anesthesia. Blood, serum, and liver homogenates from rats were used for biochemical analysis. The phytate and tannin contents were 0.38 mg/100 g and 0.15 mg/100 g, respectively. The calculated phytic acid to zinc ratio was 0.12. The respective percentage proximate components of the extract include moisture, ash, fat, protein, and carbohydrates: 10.61%, 45.42%, 5.95%, 1.81%, 13.78%, and 22.43%, respectively. Sodium, potassium, calcium, iron, magnesium, zinc, manganese, and lead were present in the extract. There was a significant increase (p<0.05) in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and acid phosphatase (ALP) activity in the groups treated with the extract compared to the control groups. Similarly, there was a significant increase (p<0.05) in serum total bilirubin and albumin concentrations in the extract treatment groups compared to control groups. On the contrary, there was a significant decrease (p<0.05) in the liver AST and ALP activity in the treatment groups compared to the control. The liver total protein and albumin concentrations showed a significant decrease (p<0.05) in the extract treatment groups compared to the control. There was a significant decrease (p<0.05) in the pack cell volume (PCV), haemoglobin (Hb), red blood cell (RBC), Mean cell volume (MCV), and platelet (PLT) levels in the animals in the extract treatment groups compared to the control group. Myristica fragrans is abundant in essential nutrients crucial for maintaining optimal physiological functions within the body, however, it is important to avoid excessive dosage or prolonged consumption which might be toxic to liver cells. Key words: Myristica, animals, tannins, phytic acid, chemical and drug Induced liver injury, minerals

Influence of Aframomum sceptrum Treatment on Hepatic Toxicity Induced by Monosodium Glutamate in Albino Rats

Monosodium glutamate (MSG) is commonly used as a culinary flavouring, although research suggest that it is toxic to people and laboratory animals, especially in high dosages. The study goal is to determine the impact of Aframomum sceptrum (ataiko) treatment on hepatic induced toxicity by MSG. Thirty-six albino rats (male) with weight of 120 to 210 g were used for the study. The rats were separated into 6 groups in which each group contains six rats. Group 1: normal control. Group 2: MSG only. Group 3 and 4 were given MSG and then treated with 250 and 350 mg/kg b.wt of A. sceptrum extract respectively. Group 5 and 6 were administered only 250 and 350 mg/kg b.wt of A. sceptrum extract, respectively. The MSG groups were given intra-peritoneal injection of MSG solution at single dose of 4253 mg/kg b.wt. A. sceptrum extract was administered three times a week for four weeks beginning two days after the MSG induction. Liver function markers such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and oxidative stress markers such as reduced glutathione (GSH) and malondialdehyde (MDA) were determined in serum and liver. Also, glucose was determined in the serum. The results showed that there were significant (p < 0.05) increased in glucose, AST, ALT and MDA in serum and liver, and decreased in GSH level in the liver of rats given MSG only when compared with normal control. However, A. sceptrum administration significantly (p < 0.05) decreased glucose, AST, ALT and MDA in the serum and liver, and increased GSH level in the liver when compared with MSG only. In conclusion, aqueous extract of A. sceptrum may have beneficial effect in MSG induced toxicity in rats by improving GSH level as well as liver function markers in a dose dependent manner.

Sodium Valproate-Induced Hyperammonemia: A Case Series in a Tertiary Care Hospital.

Sodium valproate (VPA) is an extensively used anti-convulsant, which is an effective drug for treatment of epilepsy in adults and children, as well as for conditions like migraine, bipolar disorder, mania, and trigeminal neuralgia. Sedation, vertigo, ataxia, dose-dependent tremors, headaches, and gastrointestinal side effects are the most often reported adverse effects associated with VPA. A potential life-threatening event reported with VPA is hyperammonemia (HA), which is defined as an increase in serum level of ammonia. Only 587 reported cases of HA were found in the VigiAccess database, representing a mere 0.6% of the 95,000 reported adverse events linked to VPA. Hence, this case series was conducted with emphasison monitoring of increased serum ammonia levels with or without hepatic enzymes increase for patients who are on VPA. To assess elevated serum ammonia levels following VPA administration, and to ascertain the percentage of individuals with hepatic enzymes increased who took VPA and subsequently had elevated serum ammonia levels. This study was conducted at the adverse drug reaction (ADR) monitoring centre (AMC) of the Pharmacovigilance Programme of India (PvPI) and Department of Psychiatry, Christian Medical College and Hospital (CMC&H), Ludhiana. The study comprised of 12 patients who were exclusively on VPA and exhibited symptoms related to elevated serum ammonia.An informed consent form (ICF) was provided to the patient prior to taking their personal details. Laboratory investigations were done to establish the diagnosis and liver function tests (LFTs), chiefly ALT (alanine transferase) and AST (aspartate aminotransferase) were also performed.It is a descriptive study which was for a time period of six months. Results: This study includes 12 patients who had HA confirmed by laboratory investigation. Out of these 12 patients, two patients (17%) had a corresponding increase in LFT. The average as of the patients was 53.08 years and average serum ammonia levels were 219.15. None of the patients who presented with HA progressed to hyperammonemic encephalopathy (HAE). This case series on valproate-induced HAshould be of interest to psychiatrists, physicians, internists, family medicine physicians, hospitalists, and surgeons who will have patients on VPA. Delay in recognition of HA can result in the development of potentially life-threatening complications.Rapid diagnosis and management will help in reducing the number of cases which progress to encephalopathy which is highly fatal.

Pharmacokinetics, Dose-Proportionality, and Tolerability of Intravenous Tanespimycin (17-AAG) in Single and Multiple Doses in Dogs: A Potential Novel Treatment for Canine Visceral Leishmaniasis.

In the New World, dogs are considered the main reservoir of visceral leishmaniasis (VL). Due to inefficacies in existing treatments and the lack of an efficient vaccine, dog culling is one of the main strategies used to control disease, making the development of new therapeutic interventions mandatory. We previously showed that Tanespimycin (17-AAG), a Hsp90 inhibitor, demonstrated potential for use in leishmaniasis treatment. The present study aimed to test the safety of 17-AAG in dogs by evaluating plasma pharmacokinetics, dose-proportionality, and the tolerability of 17-AAG in response to a dose-escalation protocol and multiple administrations at a single dose in healthy dogs. Two protocols were used: Study A: four dogs received variable intravenous (IV) doses (50, 100, 150, 200, or 250 mg/m2) of 17-AAG or a placebo (n = 4/dose level), using a cross-over design with a 7-day "wash-out" period; Study B: nine dogs received three IV doses of 150 mg/m2 of 17-AAG administered at 48 h intervals. 17-AAG concentrations were determined by a validated high-performance liquid chromatographic (HPLC) method: linearity (R2 = 0.9964), intra-day precision with a coefficient of variation (CV) ≤ 8%, inter-day precision (CV ≤ 20%), and detection and quantification limits of 12.5 and 25 ng/mL, respectively. In Study A, 17-AAG was generally well tolerated. However, increased levels of liver enzymes-alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT)-and bloody diarrhea were observed in all four dogs receiving the highest dosage of 250 mg/m2. After single doses of 17-AAG (50-250 mg/m2), maximum plasma concentrations (Cmax) ranged between 1405 ± 686 and 9439 ± 991 ng/mL, and the area under the curve (AUC) plotting plasma concentration against time ranged between 1483 ± 694 and 11,902 ± 1962 AUC 0-8 h μg/mL × h, respectively. Cmax and AUC parameters were dose-proportionate between the 50 and 200 mg/m2 doses. Regarding Study B, 17-AAG was found to be well tolerated at multiple doses of 150 mg/m2. Increased levels of liver enzymes-ALT (28.57 ± 4.29 to 173.33 ± 49.56 U/L), AST (27.85 ± 3.80 to 248.20 ± 85.80 U/L), and GGT (1.60 ± 0.06 to 12.70 ± 0.50 U/L)-and bloody diarrhea were observed in only 3/9 of these dogs. After the administration of multiple doses, Cmax and AUC 0-48 h were 5254 ± 2784 μg/mL and 6850 ± 469 μg/mL × h in plasma and 736 ± 294 μg/mL and 7382 ± 1357 μg/mL × h in tissue transudate, respectively. In conclusion, our results demonstrate the potential of 17-AAG in the treatment of CVL, using a regimen of three doses at 150 mg/m2, since it presents the maintenance of high concentrations in subcutaneous interstitial fluid, low toxicity, and reversible hepatotoxicity.

#1957 Microbial and metabolomic remodeling by Sichuan dark tea-based formula improves obesity-induced renal lipid metabolism disorder in mice

Abstract Background and Aims The theory of medicine-food homology is long-standing and has been widely applied in traditional Chinese medicine. The Sichuan dark tea-based medicated dietary formula (alternatively referred to as Qing, or clarity in Chinese) is previously used for its lipid-lowering properties in apoE mice. This study further investigated the renoprotective effects of Qing on diet-induced obesity (DIO) mice and explored the specific mechanisms involved. Method Male C57BL/6 mice were randomly assigned to three groups, a control group, a DIO group, and a Qing treatment group, or the Qing group, with 8 mice in each group. The mice in the control group were given normal maintenance feed and purified water, and the other two groups were fed a high-fat diet for 12 weeks to establish the DIO model. After that, high-fat diet continued in the DIO group, while the Qing group was given Qing at the same time for 12 weeks, during which period the weight of the mice was monitored and recorded every week. The mice were sacrificed after 12 weeks. Serum samples were collected and the levels of triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin were measured to evaluate liver function. In addition, renal lipids were extracted to determine the levels of TG and TC in the kidney and periodic acid-Schiff (PAS) and oil red O stainings were performed to evaluate kidney pathological injury. Western blot was performed to determine the phosphorylated AMPK (pAMPK)/AMPK ratio in the kidney tissue. RT-qPCR and Western blot were used to determine the expression of proteins related to fatty acid oxidation and key proteins related to lipid synthesis. 16SrRNA and metabolomics were applied to analyze the gut microbiota in the intestinal contents and its metabolites. Results Compared with those of the control group, the levels of liver mass (P=0.0003), serum ALT(P < 0.0001), AST (P=0.0001), TC (P=0.0191) and TG (P=0.0101) in the model group were significantly increased. Qing treatment can effectively reduce liver mass (P=0.0316), and improve AST (P=0.0012), ALT (P=0.0027), TC (P=0.0200), TG (P=0.0499) levels of mice compared to those of the DIO group. Qing treatment inhibited the expression of lipid synthesis related genes (SREBP-1, FASN and SCD1) and promoted the expression of fatty acid oxidation related genes (CPT1A, PGC1α and PPARγ) in kidneys (Fig. 1). Obesity-triggered dysfunction of structure and composition of gut microbiota were improved by Qing (Fig. 2), where the content of short-chain fatty acids, especially isovaleric acid and propionic acid, were also restored (Fig. 3). Conclusion Our data suggested that Sichuan dark tea-based medicated dietary formula may improve renal lipid metabolism by regulating gut microbiota and the levels of intestinal short-chain fatty acids, thereby protecting obesity-related kidney injury. Isovaleric acid and propionic acid may be the metabolites key to its regulation of gut microbiota.

Use of Bacillus subtilis multiplicate in the water used for biofloc formation: Growth, hemato-biochemistry, intestinal bacteria colonies, and bacterial resistance evaluations of Nile tilapia

Probiotics in the biofloc technology (BFT) system improve fish growth and immune response and promote a favorable intestinal microbiota balance. This study aimed to investigate the growth, hemato-biochemical parameters, bacterial resistance, and the number of intestinal bacteria colonies of Nile tilapia (6.23 g) reared in the BFT system with graded levels of Bacillus subtilis multiplicate (BSM) in the water. The multiplication of these microorganisms was performed in a biofactory. Fish were distributed into four different groups with graded BSM concentrations in the water of 0.00, 0.25, 0.50, and 0.75% (or 0; 750; 1500; and 2250 mL; called BSM0 (control), BSM25, BSM50, and BSM75, respectively). The experimental procedure had 45 days for growth performance evaluations and seven additional days of bacterial challenge with Aeromonas hydrophila. The experimental design was randomized into four treatments in triplicate (n = 20 fish per tank; initial stocking density of 0.50 kg m−3). Survival was 100% before and after the bacterial challenge. Increasing BSM in the BFT system had a positive linear effect on nitrite, nitrate, settled solids, hemoglobin, and hematimetric indices. BSM50 showed the highest specific growth rate, weight gain, intestinal total bacteria, and B. subtilis counts and the lowest feed conversion rate. In BSM50 and BSM75, liver glycogen levels and aspartate aminotransferase (AST) activity were higher and lower, respectively, than in the other treatments. Plasma total cholesterol, total proteins, albumin, and skin mucus total proteins and albumin were highest in BSM25. After the bacterial challenge, the number of lesions was lower in BSM75 than in the control group. In conclusion, we recommended BSM50 because it increased the growth performance and bacterial colonization in the intestine. It also decreased liver AST activity in Nile tilapia reared in the BFT system without compromising water quality and hematological and plasmatic parameters.

Mechanism of total saponins of Panax japonicus against liver injury induced by acetaminophen in mice based on ERK/NF-κB/COX-2 signaling pathway

This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1β), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1β, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1β, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1β, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.

Antioxidant activity and toxicological implications of the aqueous extract of Azanza garckeana fruit pulp in female wistar rats

This study examined the antioxidant activity as well as the safety profile of Azanza garckeana aqueous extract in female Wistar rats. Following the random distribution of 28 female Wistar rats (mean weight = 159.25 ± 3.32 g) into four (4) groups labelled (A-D) containing seven rats (animals) each, a daily administration of 0.5 mL distilled water was orally given to the rats in group A, while the aqueous extract of A. garckeana fruit pulp were given orally at 125, 250 and 500 mg/kg to rats in groups B, C and D respectively for 21 days. Some antioxidant activities as well as kidney and liver function indices were examined on the rat using established methods. All liver function indices assayed for showed no significant (p > 0.05) difference in comparison to the control. The concentration of liver enzyme revealed no significant (p > 0.05) difference in liver alanine aminotransferase, liver aspartate aminotransferase, lactate dehydrogenase and liver alkaline phosphatase at 500 mg/kg in comparison to the control group. Conversely, all kidney functions indices show significant increase (p < 0.05) following extract administration, indicating potential effects on kidney function. Significant decrease (p< 0.05) was observed in the level of kidney and liver reduced glutathione and kidney malondialdehyde while kidney and liver superoxide dismutase as well as liver malondialdehyde significantly increased (p<0.05). Overall, aqueous fruit pulp extract of A. garckeana shows no damaging effect on liver indices at the investigated dosage. However, it may have a significant side effect on the kidney due to the biochemical alterations observed in the kidney function indices at the investigated dosages.

Aqueous extract of Epimedium sagittatum (Sieb. et Zucc.) Maxim. induces liver injury in mice via pyroptosis

Ethnopharmacological relevanceEpimedium sagittatum (Sieb. et Zucc.) Maxim. has been used traditionally in Asia. It can dispel wind and cold, tonify the kidney, and strengthen bones and tendons. However, adverse effects of E. sagittatum have been reported, and the underlying mechanisms remain unclear. Aim of the studyThis study aimed to investigate liver injury caused by an aqueous extract of E. sagittatum in Institute of Cancer Research (ICR) mice and explore its potential mechanisms. Materials and methodsDried E. sagittatum leaves were decocted in water to prepare aqueous extracts for ultra-high performance liquid chromatography analysis. Mice were administered an aqueous extract of E. sagittatum equivalent to either 3 g raw E. sagittatum/kg or 10 g raw E. sagittatum/kg once daily via intragastric injection for three months. The liver weights and levels of the serum biochemical parameters including alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total bilirubin (TBIL), and alkaline phosphatase were measured. Hematoxylin-eosin staining was performed for histopathology. Apoptosis was detected using the TUNEL apoptosis assay kit. IL-1β was detected using ELISA kits. Proteomics was used to identify the differentially expressed proteins. Western blot analysis was performed to determine the levels of proteins significantly affected by the aqueous extract of E. sagittatum. ResultsE. sagittatum treatment increased the liver weights and liver coefficients, and ALT and AST levels significantly increased (p < 0.05). A high dose of E. sagittatum significantly increased LDH and TBIL levels (p < 0.05). Ruptured cell membranes and multiple sites of inflammatory cell infiltration were also observed. No evidence of apoptosis was observed. IL-1β levels were significantly increased (p < 0.05). The expressions of PIK3R1, p-MAP2K4, p-Jun N-terminal kinase (JNK)/JNK, p-c-Jun, VDAC2, Bax, and CYC were upregulated, whereas that of Bcl-2 was inhibited by E. sagittatum. The expression of cleaved caspase-1 was significantly increased; however, its effects on GSDMD and GSDMD-N were significantly decreased. The expression levels of cleaved caspase-3 and its effector proteins GSDME and GSDME-N significantly increased. ConclusionsOur results suggest that the aqueous extract of E. sagittatum induces liver injury in ICR mice after three months of intragastric injection via inflammatory pyroptosis.

Didymin ameliorates ulcerative colitis-associated secondary liver damage by facilitating Notch1 degradation

BackgroundDidymin is a dietary flavonoid originally discovered by our group as a potent anti-ulcerative colitis (UC) agent. However, whether didymin plays a protective role in UC-associated inflammatory liver injury is still unclear. PurposeThis study aimed to evaluate the therapeutic potential of didymin on UC-associated inflammatory liver injury and explore the underlying mechanism. Study design and methodsColitis model was established in C57BL/6 mice by exposure to DSS, and didymin was administrated intragastrically for consecutive 10 days. The inflammatory liver injury was assessed by levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum and histopathological damage in the liver. In vitro Kupffer cells and RAW264.7 cells challenged with lipopolysaccharides (LPS) were used to explore the modulatory activity of didymin on pro-inflammatory cytokines secretion and Notch1 signaling pathway activation. ResultsDidymin significantly mitigated liver coefficiency, ALT and AST levels in serum, and the hepatic histopathological damage caused by DSS-induced acute and chronic colitis. The mRNA expressions of pro-inflammatory factors including Tnf, Il1, and Il6 in liver tissues, Kupffer cells, and RAW264.7 cells stimulated by the influx of LPS was significantly deprived after didymin treatment. Mechanistically, didymin obstructed the protein expression, nuclear translocation of notch intracellular domain 1 (Notch1-ICD) and mRNA expression of hairy and enhancer of split 1 (Hes1). Further, the inhibitory mechanism of the Notch1-Hes1 pathway was dependent on c-Cbl-mediated Notch1-ICD lysosomal degradation. ConclusionOur study verified for the first time that didymin could prevent UC-associated diseases, such as inflammatory liver injury, and the mechanism was related to facilitating Notch1 lysosomal degradation rather than proteasome degradation via promoting protein expression of c-Cbl in macrophages. Our findings that the inhibition of Notch1 signaling transduction helps to alleviate UC-associated liver injury provides possible therapeutics for the treatment of colitis and also furnishes a research paradigm for the study of flavonoids with similar structures.

Independent and additive effects of binge drinking and obesity on liver enzymes: a cross-sectional analysis using the Korean National Health Insurance Service data.

Binge drinking (BD) has been associated with elevated liver enzymes, but the joint association of BD and adiposity with liver enzymes is understudied. We aimed to examine the combined association of BD and obesity with elevated liver enzymes. Data were obtained from 285,600 patients in the Korean National Health check-up program during 2009-2015. Level I BD (BDI) was defined as alcohol consumption of >60 g (men) or >40 g (women) on one occasion in the previous year. High-intensity BD (HIBD) corresponded to at least two times the BDI levels. General and abdominal obesity were defined by body mass index and waist circumference. Logistic regression was used to examine the independent and joint associations of BD and obesity with elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels. Relative excess risk (RERI), attributable proportion (AP), and synergy index (SI) were calculated to estimate the additive interaction effects. The mean age was 42.1 ± 0.03 years and 50.2% were women. Elevated ALT [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.02-1.16], AST (OR 1.16, 95% CI 1.11-1.23), and GGT (OR 1.84, 95% CI 1.05-1.94) were associated with HIBD. Higher odds of elevated ALT (OR 3.57, 95% CI 3.43-3.71), AST (OR 3.47, 95% CI 3.37-3.58), and GGT (OR 2.10, 95% CI 1.98-2.12) were observed in individuals with general obesity. A similar trend was observed for abdominal obesity. The RERI, AP, and SI for the interaction effect of BD and general obesity were 23%, 7%, and 13% for elevated AST levels, and 67%, 24%, and 58% for elevated GGT levels, respectively. Similar effects were observed for the interaction between BD and abdominal obesity. Obesity aggravated the odds of elevated liver AST and GGT levels in HIBD.

Prior drug allergies are associated with worse outcome in patients with idiosyncratic drug-induced liver injury: A machine learning approach for risk stratification

The impact of prior drug allergies (PDA) on the clinical features and outcomes of patients who develop idiosyncratic drug-induced liver injury (DILI) is largely unknown. We aimed to assess the clinical presentation and outcomes of DILI patients based on the presence or absence of PDA and explore the association between culprit drugs responsible for DILI and allergy. We analysed a well-vetted cohort of DILI cases enrolled from the Spanish DILI Registry. Bootstrap-enhanced least absolute shrinkage operator procedure was used in variable selection, and a multivariable logistic model was fitted to predict poor outcomes in DILI. Of 912 cases with a first episode of DILI, 61 (6.7%) had documented PDA. Patients with PDA were older (p = 0.009), had higher aspartate aminotransferase (AST) levels (p = 0.047), lower platelet count (p = 0.011) and higher liver-related mortality than those without a history of drug allergies (11% vs. 1.6%, p < 0.001). Penicillin was the most common drug associated with PDA in DILI patients (32%). A model including PDA, nR-based type of liver injury, female sex, AST, total bilirubin, and platelet count showed an excellent performance in predicting poor outcome in patients from the Spanish DILI Registry (area under the ROC curve [AUC] 0.887; 95% confidence interval [CI] 0.794 – 0.981) and the LATINDILI Network (AUC 0.932; 95% CI 0.884 – 0.981). Patients with suspected DILI should be screened for PDA as they would require a close monitoring for early detection of worsening clinical course.

Regulatory mechanism of the six-method massage antipyretic process on lipopolysaccharide-induced fever in juvenile rabbits: A targeted metabolomics approach

ObjectiveTo investigate the mechanism of the six-method massage antipyretic process (SMAP) and its influence on the body's metabolic state. MethodsThe random number table method was used to divide 24 New Zealand 2-month-old rabbits with qualified basal body temperature into a control group, model group and massage group (n = 8 per group). The model group and massage groups were injected with 0.5 μg/ml lipopolysaccharide (1 ml/kg) into the auricular vein, and the control group was injected with the same amount of normal saline at the same temperature. One hour after modelling, the massage group was given SMAP (opening Tianmen, pushing Kangong, rubbing Taiyang, rubbing Erhougaogu, clearing the Tianheshui and pushing the spine). The change of anal temperature 5 h after moulding was recorded to clarify the antipyretic effect. ResultsAfter modelling, the rectal temperature of the juvenile rabbits in the three groups increased. The rectal temperature of the model group was higher than that of the control group 5 h after modelling, and the rectal temperature of the massage group was lower than that of the model group (P < 0.05). The antipyretic mechanism is related to the regulation of the synthesis of phenylalanine, tyrosine and tryptophan, as well as the pentose phosphate pathway. Compared with the model group, the plasma interleukin (IL)-1, IL-6, interferon-gamma, toll-like receptor 4, nuclear factor κB, the mechanistic target of rapamycin complex 1, indoleamine 2,3-dioxygenase 1, aryl hydrocarbon receptor, liver aspartate transaminase (AST), alanine transaminase (ALT) and l-glutamate dehydrogenase (L-GLDH) expression in the massage group were significantly decreased (P < 0.05). Compared with the model group, the massage group had significantly reduced AST, ALT and L-GLDH expression in plasma (P < 0.05). ConclusionThe mechanism of SMAP therapy is related to regulating the expression of peripheral inflammatory factors and metabolic pathways.

The gut-liver axis perspective: Exploring the protective potential of polysaccharides from Cistanche deserticola against alcoholic liver disease

The primary objective of this study is to investigate the potential mechanism behind the protective effect of Cistanche deserticola polysaccharides (CP) against alcoholic liver disease (ALD). Multiple chromography techniques were employed to characterize CP from polysaccharide, the molecular weight distribution of polysaccharides, monosaccharide composition, isomeric hydrogen and isomeric carbon, in order to clarify the material basis of CP. To create the ALD mouse model, we utilized the well-established Lieber-DeCarli alcoholic liquid feed method. Findings from the study revealed that CP administration resulted in significant improvements in intestinal permeability, upregulation of barrier proteins expression, and reduced levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mouse liver and serum. Additionally, CP treatment reduced the presence of inflammatory cytokines both in serum and liver while enhancing the activity of antioxidant enzymes in the liver. Furthermore, CP effectively reduced alcohol-induced oxidative damage by downregulating Keap1 protein levels in the liver, leading to increased expression of Nrf2 protein. The 16S rDNA sequencing results revealed that CP significantly restored the intestinal microbiota composition in ALD mice. These findings establish a strong association between gut microbiota and liver injury indicators, highlighting the potential of CP in preventing and treating ALD by modulating the gut-liver axis.

Effects of cadmium on liver function in turtle Mauremys reevesii.

This research was designed to investigate the effects of cadmium (Cd) on liver function in turtle Mauremys reevesii. Turtles were divided into 4 groups at random. The turtles were injected intraperitoneally with Cd at 0, 7.5, 15, 30mgkg-1 Cd chloride separately. Liver index was calculated. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the content of TP in liver were examined with biochemical methods. The results indicated that the liver index of turtles changed obviously only at higher dose and longer time. The activities of ALT and AST in liver increased with prolongation of exposure time in a dose-dependent manner. TP content in liver was lower than that in the control. In summary, Cd had an obvious toxic effect on liver tissues of freshwater turtle Mauremys reevesii, and it was dose dependent with the extension of exposure time. But the results also showed that the turtle had strong tolerance to Cd.

Sichuan Dark Tea-Based Medicated Dietary Formula Improves Obesity-Induced Renal Lipid Metabolism Disorder in Mice by Remodeling Gut Microbiota and Short-Chain Fatty Acid Metabolism

To investigate the renoprotective effects of a Sichuan dark tea-based medicated dietary formula (alternatively referred to as Qing, or clarity in Chinese) on mice with diet-induced obesity (DIO) and to explore the specific mechanisms involved. Male C57BL/6 mice were randomly assigned to three groups, a control group, a DIO group, and a Qing treatment group, or the Qing group, with 8 mice in each group. The mice in the control group were given normal maintenance feed and purified water, and the other two groups were fed a high-fat diet for 12 weeks to establish the DIO model. After that, high-fat diet continued in the DIO group, while the Qing group was given Qing at the same time for 12 weeks, during which period the weight of the mice was monitored and recorded every week. The mice were sacrificed after 12 weeks. Serum samples were collected and the levels of triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin were measured to evaluate liver function. In addition, renal lipids were extracted to determine the levels of TG and TC in the kidney and periodic acid-Schiff (PAS) and oil red O stainings were performed to evaluate kidney pathological injury. Western blot was performed to determine the phosphorylated AMPK (pAMPK)/AMPK ratio in the kidney tissue. RT-qPCR and Western blot were used to determine the expression of proteins related to fatty acid oxidation, including acetyl-CoA carboxylase 1 (ACC1), carnitine acyltransferase 1 (CTP1), peroxisome proliferators-activated receptor γ (PPARγ), peroxisome proliferators-activated receptor-1 α (PPAR1α), sterol-regulatory element binding proteins (SREBP-1), and key proteins related to lipid synthesis, including fatty acid synthase (FASN) and stearoyl-coenzyme A desaturase 1 (stearoyl-CoA desaturase) in the kidney tissue. 16SrRNA and metabolomics were applied to analyze the gut microbiota in the intestinal contents and its metabolites. Compared with those of the control group, the levels of liver mass (P=0.0003), serum ALT (P<0.0001) and AST (P=0.0001), and kidney TC (P=0.0191) and TG (P=0.0101) of the DIO group were significantly increased and there was lipid deposition in the kidney. Compared with those of the DIO group, mice in the Qing group showed effective reduction in liver mass (P=0.0316) and improvements in the abnormal serum levels of AST (P=0.0012) and ALT (P=0.0027) and kidney TC (P=0.0200) and TG (P=0.0499). In addition, mice in the Qing group showed significant improvement in lipid deposition in the kidney. Qing group showed increased pAMPK/AMPK ratio in comparison with that of the DIO group. In comparison with those of the control group, mice in the DIO group had upregulated expression of lipid synthesis-related genes and proteins (SREBP-1, FASN, and SCD1). As for the fatty acid oxidation-related genes and proteins, DIO mice showed upregulated expression of ACC1 and downregulated expression of CPT1A, PPARγ, and PGC1α in comparison with those of the control group. In the Qing goup, improvements in regard to all these changes were observed. The Qing group demonstrated improvement in the disrupted homeostasis of the gut microbiota. Short-chain fatty acids in the cecal contents, especially isovaleric acid and propionic acid, were also restored. Sichuan dark tea-based medicated dietary formula may improve renal lipid metabolism by regulating gut microbiota and the levels of intestinal short-chain fatty acids, thereby protecting obesity-related kidney injury. Isovaleric acid and propionic acid may be the metabolites key to its regulation of gut microbiota.

PSVI-8 Bisphosphonate Pharmacokinetics in Juvenile Horses

Abstract Bisphosphonates alter bone metabolism via inhibition of osteoclastic bone resorption. Although bisphosphonates are beneficial to treat bone disease, extra-label use in healthy juvenile horses may interfere with normal bone metabolism. The objective was to determine plasma pharmacokinetics of the bisphosphonate clodronate disodium (CD) following a single intramuscular dose to better define the time course of CD in juvenile horses. Ten yearling Quarter Horses (334 ± 18 kg, 504 ± 13 d of age) were used to test the hypothesis that juvenile horses would have faster clearance rate of CD compared with previously published data in adult horses. Horses were placed in individual stalls, jugular intravenous catheters were inserted, and an initial blood sample (0 h) was collected. Horses were administered CD intramuscularly at 1.8 mg/kg BW per label. Plasma samples were collected at 0.5, 1, 3, 6, 12, 24, 48, and 72 h post-administration. Plasma concentration of clodronate was determined by liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were calculated using a two-compartment model. Blood chemistry parameters [blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALKP), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and creatine kinase (CK)] were determined via a commercial laboratory. Included blood chemistry parameters were analyzed for an effect of time using PROC Mixed of SAS. Clodronate was detected in plasma up to 72 h post-administration. Maximum plasma concentration (43,971 ± 25,920 ng/mL) was reached at 0.5 h post-administration. Analysis revealed bicompartmental kinetics with distribution and terminal half-lives of 1.9 ± 0.4 h and 24.4 ± 4.3 h, respectively. Area under the curve to last sample was 22,755 ± 11,426 ng*h/mL and extrapolated to infinity was 26,778 ± 12,465 ng*h/mL. Blood chemistry parameters varied over time within normal ranges. Markers of renal function, BUN and creatinine, decreased from h 0 to h 72 (P &amp;lt; 0.01). Liver function markers ALKP and AST were not affected by CD treatment (P &amp;gt; 0.27). However, GGT and CK changed over time (P &amp;lt; 0.01), with GGT greater at 48 h than other time points, and CK increasing from 0.5 to 24 h before decreasing by 72 h but remaining above baseline. Plasma clodronate concentrations were greater in juvenile horses than previously reported in mature horses (Krueger et al., 2020, Equine Vet J.; Knych et al., 2022, Equine Vet J.). Further, the observed bicompartmental kinetics differed from the linear kinetics previously reported in mature horses whereby juvenile horses from the current study had greater exposure to CD over time as indicated by a longer terminal half-life. Moreover, the single intramuscular dose of CD (1.8 mg/kg BW) did not cause markers of kidney or liver function to deviate from normal ranges in juvenile Quarter Horses.

Studying the Effect of COVID-19 on Liver Enzymes and Lipid Profile in Iraqi Recovering Patients

The Covid-19 virus disease has been shown to affect numerous organs and systems including the liver. The study aimed to compare lipid profiles and liver enzyme levels in individuals who had recovered from Covid-19 infection. To achieve the study objectives, liver Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline phosphatase (ALP), Random Blood Sugar (RBS) and Lipid profile which include cholesterol, High-Density Lipoprotein (HDL), Triglycerides (T.G), Low-Density Lipoprotein (LDL), and Very low-density Lipoprotein (VLDL) were determined. One hundred twenty serum samples were obtained, of which fifty samples were utilized as the control healthy persons (not affected by COVID) and seventy samples came from COVID-19 patients who had recovered. Liver enzymes showed a significant increase in serum AST, ALT, and ALP between the two groups (p-values) of 0.001. The lipid profile demonstrated notable ariations which showed an increase in cholesterol, TG, LDL, and VLDL., as well as a decrease in HDL level in the recovered patients’ group compared to the control (p-values) with a value of 0.001. There were no significant differences in RBS between the recovered patients’ group as compared with the control, (p-value) (0.062). Also, body mass index )BMI( and age showed no significant differences. This study concluded that Covid 19 survivors experienced issues with their lipid profiles and liver enzymes

Effects of copper exposure and recovery in juvenile yellowtail kingfish (Seriola lalandi): Histological, physiological and molecular responses

This study investigated the physiological responses to copper toxicity in liver and gill of juvenile yellowtail kingfish by exposing to 0 (control), 0.0672, 0.12, 0.214, 0.384, 0.672, 1.20, or 2.14 mg/L copper sulfate for 7 days and then recovered for 14 days. The histopathology, enzyme activities and differential gene expression were detected. The results indicate the safe concentration value of copper for juvenile yellowtail kingfish is 0.083 mg/L. Copper exposure caused structural damage to gill and liver, and could be disappeared or restored after the recovery period. Copper exposure enhanced the Cu,Zn superoxide dismutase (Cu/Zn-SOD) and glutathione peroxidase (GSH-Px) activities and the malondialdehyde (MDA) level in liver. However, with increasing copper concentrations, liver aspartate transaminase (AST) and gill Na+/K+-ATPase activities were at first enhanced and then inhibited. Serum lysozyme (LZM) and Cu/Zn-SOD activities were enhanced at low copper concentrations but inhibited at high concentrations, and the activities of alanine transaminase (ALT) and AST significantly increased at greater copper concentrations. After the recovery period, only liver Cu/Zn-SOD activity returned to control level. In contrast, liver GSH-Px activity and MDA levels and gill Na+/K+-ATPase activity, serum LZM and AST activities remained significantly higher than control, but liver AST activity, serum ALT, and Cu/Zn-SOD activities were significantly lower than control. We constructed the gene regulatory networks of molecular pathways in liver and gill in response to copper exposure. The DEGs were enriched mainly in the pathway of lipid metabolism in liver and pathway of oxidative phosphorylation in gill, indicating these respective pathways are involved in the response to copper stress in this species. The present results elucidate some histological, physiological, and molecular mechanisms underlying copper-exposure stresses in yellowtail kingfish, which could help guide the safe utilization of copper sulfate in disease control of farmed individuals.

Associations between Periodontal Status and Liver Function in the Japanese Population: A Cross-Sectional Study.

A relationship between periodontitis and liver function has been suggested. Indeed, patients with severe periodontal disease have been found to be more prone to liver dysfunction. The periodontal inflammatory surface area (PISA) has been shown to be a useful indicator of periodontal and systemic diseases. However, little information is available regarding whether the PISA is associated with liver function markers, such as gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). This study aimed to clarify relationship between liver function markers, AST, ALT, and GGT, and PISA level in a cross-sectional study. The subjects were recruited between 2018 and 2021 at the Medical and Dental Collaboration Center of Kanagawa Dental College Hospital. A periodontal clinical examination was performed, and the PISA was calculated. Peripheral blood samples were collected, and serum levels of liver function markers were measured. The levels of liver function markers were examined in different values of PISA. Participants with high PISA scores were more likely to have increased GGT levels while AST and ALT were not changed with PISA. Increased GGT was found in 10.8% and 29.4% (p = 0.0056), increased AST in 48.2% and 52.9% (p = 0.62), and increased ALT in 35.2% and 47.0% (p = 0.20) among <300 mm2 and ≧300 mm2 PISA groups, respectively. It was found that males with a PISA of 300 mm2 or higher had an elevated level of serum GGT. In conclusion, elevated GGT was found in the high PISA group, particularly in males, while AST and ALT did not differ by PISA.