Alanine Transferase Levels Research Articles

Ultrasonication coupled to enzymatic hydrolysis of soybean okara proteins for producing bioactive and bioavailable peptides

This work was aimed to explore the antioxidative properties, bioavailability and the safety of bioactive peptides obtained by the enzymatic hydrolysis of ultrasound-treated (UO) and untreated (nUO) soybean okara proteins. Particularly, the peptidomic profiles of both hydrolysates were examined using an untargeted metabolomics technique for suspect screening that was specifically designed for the profiling of short-chain peptides and relied on ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and bioinformatics.Next, both UO and nUO hydrolysates reduce Dipeptidyl peptidase-IV (DPP-IV) enzyme activity until 39.54 ± 0.26 % and 43.29 ± 0.36 % respectively and inhibit angiotensin converting enzyme (ACE) activities by 30.54 ± 0.42 % and 30.76 ± 0.02 %, respectively. Moreover, they demonstrate to exerted antioxidant properties. Particularly, they show a comparable in vitro antioxidant activity but when the oxidative stress is induced by H2O2 in Caco-2 cells, UO hydrolysate is more active in lowering the levels of reactive oxygen species (ROS) and of lipid peroxidation induced of 48% and 20% respectively.In addition, UO- and nUO-derived peptides trans-epithelial transported by human differentiated intestinal cell monolayer, were identified. Lastly, the possible hepatotoxicity of UO and nUO hydrolysates in HepG2 cells has not been observed by measuring alanine transferase (ALT) and aspartate transferase (AST) levels and cytotoxic effects.

6898 A Case Report Of Drug-Induced Liver Injury Secondary To Sublingual Estradiol In A Transgender Woman

Abstract Disclosure: F. Manas: None. E. Davydov: None. A. Caines: None. K. Estrada: None. J.E. Shill: None. Drug-induced liver injury (DILI), the leading cause of acute liver failure in the United States, occurs in response to a medication or natural compound. Estrogens can lead to idiosyncratic DILI. According to LiverTox [livertox.nih.gov], estrogen has a likelihood score of A (highly likely) to cause DILI, whereas spironolactone has a likelihood score of D (rare). The current formulations of estrogens usually produce a mixed or cholestatic pattern of liver enzyme elevations, however very early, the ALT levels can be markedly elevated (5- to 20-fold). One can be asymptomatic. Often the liver injury resolves after removing the offending agent. We present a case of DILI with elevations of both alanine transferase (ALT) and aspartate transferase (AST), secondary to sublingual estradiol (E2). A 23-year-old transgender female presented for feminizing gender-affirming care. She was started on sublingual E2 2 mg once daily and spironolactone 100 mg orally twice daily. Approximately 14 weeks later, sublingual E2 was increased to 2 mg twice daily for a below-target E2 level, and spironolactone was decreased to 50 mg twice daily due to gas and nausea. Routine blood work three weeks later showed elevated liver function tests (LFTs) in a hepatocellular pattern with ALT of 216 IU/L (normal:<52IU/L), AST of 223 IU/L (normal:<35 IU/L), with normal total bilirubin and alkaline phosphatase. LFTs were normal six months prior. At the time of liver injury, she had consumed six alcoholic beverages in the previous fourteen days, and two doses of acetaminophen. She had no personal history of autoimmunity and no family history of liver disease. Acute hepatitis screen was normal. Abdominal US with liver Doppler was unremarkable. E2 and spironolactone were discontinued. Evaluation by hepatology lead to a diagnosis of DILI from sublingual E2, based on the temporal relationship between initiation of E2 and LFT elevation. Other potential causes of elevated LFTs were excluded. Although she reported alcohol use, the AST/ALT elevation was not in a classic 2:1 pattern. Three weeks after cessation of E2 and spironolactone, her LFTs normalized. Spironolactone was resumed along with E2 by patch, but due to skin-adherence issues she was transitioned to injectable E2 valerate. Her LFTs have remained normal since. This case illustrates a rare but potentially dangerous adverse event of DILI secondary to sublingual E2. Due to the low incidence of liver injury in various studies of individuals with gender incongruence on hormone therapy, current evidence does not support routine liver enzyme monitoring. Clinicians should be aware of the potential risk of liver injury and counsel patients accordingly. As in this case, patients may be successfully rechallenged with the offending DILI medication. Further studies on different formulations of hormone therapy and their effects on the liver would be beneficial in this unique population. Presentation: 6/2/2024

Aloe vera leaf (Aloe barbadensis) iron-oxide nanoparticles improved growth performance, immune response and survival of African sharptooth catfish (Clarias gariepinus) challenged with Aeromonas hydrophilia

ABSTRACT Nano-sized essential minerals and nutrients synthesized from plant extracts are being explored for their impact on growth, immune stimulation, and overall fish health. This study evaluated the growth performance, health, and survival of African catfish, Clarias gariepinus, particularly when challenged with Aeromonas hydrophila. Biosynthesized Aloe vera leaf iron oxide nanoparticles (ANP) were confirmed by ultra-violet spectroscopy, Fourier-transform infrared spectroscopy, and scanning electron microscopy as nanoparticles. The ANPs were added to the basal diet at 0, 40, 80, 120, and 160 mg/kg, forming five treatments. The fish were fed to apparent satiation twice daily for 84 days. Results showed that dietary ANP improved weight gain, specific growth rate, protein efficiency ratio, and feed conversion ratio significantly with increasing levels of the nanoparticles. Fish fed 160 mg/kg ANP diet had a weight gain of 102.12 ± 18.91 g, while fish fed the control diet had a weight gain of 78.89 ± 22.2 g. Fish quality indices, including head-to-body percentage, visceral-somatic ratio, and flesh ratio, were similar (p > .05) across treatments. Supplementation of ANP improved significantly fish carcass quality and survival rate compared to the control diet. Fish fed nanoparticle diets had significantly different (p < .05) moisture, ash, and protein contents across all treatments. The fat content decreased with increasing nanoparticle levels, with the control diet showing the highest value (14.54%) and 160 mg/kg ANP diet the lowest (12.94%). Dietary ANP also improved carcass iron and zinc contents significantly. Additionally, ANP increased packed cell volume, red blood cells, white blood cells, hemoglobin, and erythrocyte sedimentation count more than the control diet. Alanine transferase, aspartate transferase, catalase, and superoxide dismutase levels increased with ANP in the diets. Fish-fed ANP diets had higher (p < .05) total serum protein than fish fed the control diet. ANP diets reduced blood glucose levels significantly, and cholesterol levels decreased marginally with increasing nanoparticle levels. Conclusively, ANP positively influenced the growth, immunity, and survival of C. gariepinus.

Depletion of hepatic glutathione and adenosine by glucocorticoid exposure in Wistar rats is pregnancy-independent

Liver diseases have gained increasing attention due to their substantial impact on health, independently as well as in association with cardio-metabolic disorders. Studies have suggested that glutathione and adenosine assist in providing protection against oxidative stress and inflammation while glucocorticoid (GC) therapy has been associated with chronic inflammatory disorders, even in pregnancy. The implications of Glucocorticoid exposure on maternal health and fetal growth is a concern, however, the possible role of glutathione and adenosine has not been thoroughly investigated. The study therefore hypothesize that exposure to glucocorticoids leads to depletion of hepatic glutathione and adenosine levels, contributing to oxidative stress and tissue injury. Additionally, we aim to investigate whether the effects of glucocorticoids on hepatic health are pregnancy dependent in female rats. Twelve Pregnant and twelve age-matched non-pregnant rats were used for this study; an exogenous administration of glucocorticoid (Dex: 0.2 mg/kg) or vehicle (po) was administered to six pregnant and six non-pregnant rats from gestational day 14 to 19 or for a period of 6 days respectively. Data obtained showed that GC exposure led to a decrease in hepatic glucose-6-phosphate dehydrogenase, glutathione peroxidase, GSH/GSSG ratio and adenosine content in both pregnant and non-pregnant rats. In addition, increased activities of adenosine deaminase and xanthine oxidase, along with increased production of uric acid and increased levels of lactate dehydrogenase, aspartate aminotransferase, alanine transferase, alkaline phosphatase and gamma-glutamyl transferase were observed. In summary, the study indicates that GC-induced liver damage is underlined by depleted hepatic adenosine and glutathione levels as well as elevated markers of tissue inflammation and/or injury. Furthermore, the findings suggest that the effects of GC exposure on hepatic health are pregnancy independent.

Antioxidant Effects of Whey Protein as a Dietary Supplement to Alleviate Cadmium-Induced Oxidative Stress in Male Wistar Rats

The liquid whey is a byproduct produced during cheese making. Cadmium is a highly hazardous heavy metal with cumulative toxic effects. The present research work was done to clarify the possible role of whey proteins in alleviating cadmium-induced oxidative stress. The used rats were allotted equally and randomly into three experimental groups; untreated control, cadmium-exposed, and cadmium-exposed and whey protein-administered groups. The biochemical and haematological assays of rats exposed to cadmium (group 2) manifested significant alterations compared to those of untreated control animals. Concerning the biochemical serum profile, group 3 animals showed relatively increased levels of total proteins, significant increments of total thiols, glutathione, total antioxidant capacity (TAC), and catalase, and significant decrements in the levels of blood cadmium, alanine transferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), creatinine, urea, bilirubin, hydrogen peroxide (H2O2), and malondialdehyde (MDA) compared to the animals exposed to cadmium (group 2). Homogenates of liver and kidney tissues obtained from group 3 animals demonstrated similar results to that revealed by the serum assay. It was concluded that whey proteins as a dietary supplement can offer potential antioxidant properties that enable these supplementary proteins to alleviate cadmium-induced oxidative stress.

Incidence and characteristic of deep venous thrombosis in hospitalized chronic heart failure patients.

This study was conducted to investigate the incidence of deep venous thrombosis (DVT), outcomes and its characteristics in patients with chronic heart failure (CHF) in a retrospective setting. Patients died of cardiac shock or acute exacerbation of heart failure (HF), admitted to intensive care unit (ICU) due to acute exacerbation of HF, patients decided to withdraw treatment and return home due to acute exacerbation of HF. From January 2015 to June 2022, we admitted 359 patients diagnosed with CHF, and lower limb ultrasonography was performed for the examination of DVT after admission. The incidence of DVT was recorded and patients with known risk factors of VTE were identifiedand excluded after incidence of DVT was calculated. Patients' clinical data were thencollected. The occurrence of DVT was 10.0% (36/359), as calf intramuscular vein thrombosis was the main constitution (n = 28, 75%). DVT patients with other factors (carcinoma, surgery, stroke, previous history of DVT) constituted a considerable part (33.3%, 12/36). Age, history of Diabetes Mellitus (DM), levels of DDi (D-Dimer), levels of alanine transferase (ALT) and left ventricular end-diastolic diameter (LVEDd) were independent predictors or risk factors of DVT in CHF patients, while chronic kidney disease (CKD) stage 1-4, white blood cell (WBC) and direct oral anticoagulant (DOAC) were protective factors. Incidence of DVT was correlated with a poor outcome of CHF patients (Pearson Chi-Square test, Value 19.612, P < 0.001). In this retrospective study, incidence of DVT was found to be relatively high among hospitalized CHF patients, while patients with DVT was associated with a poor prognosis.

Artificial Intelligence in Early Diagnosis of Preeclampsia.

Every day, 810 women die of preventable causes related to pregnancy and childbirth worldwide, and preeclampsia is among the top three causes of maternal deaths. To develop a diagnostic system with artificial intelligence for the early diagnosis of preeclampsia. This retrospective study included pregnant women who were screened for the inclusion criteria on the hospital's database, and the sample consisted of the data of 1158 pregnant women diagnosed with preeclampsia and 9194 pregnant women who were not diagnosed with preeclampsia at Kahramanmaras Necip Fazıl City Hospital Gynecology and Pediatrics Additional Service Building, Kahramanmaras/Turkey. The statistical analysis was performed using the Statistical Package for social sciences (SPSS) version 22 for windows. Artificial intelligence models were created using Python, scikit-learn, and TensorFlow. The model achieved 73.7% sensitivity (95% confidence interval (CI): 70.2%-77.1%) and 92.7% specificity (95% CI: 91.7%-93.6%) on the test set. Furthermore, the model had 90.6% accuracy (95% CI: 90.1% - 91.1%) and an area under the curve (AUC) value of 0.832 (95% CI: 0.818-0.846). The significant parameters in predicting preeclampsia in the model were hemoglobin (HGB), age, aspartate transaminase level (AST), alanine transferase level (ALT), and the blood group. Artificial intelligence is effective in the prediction and diagnosis of preeclampsia.

The Modulation of Phospho-Extracellular Signal-Regulated Kinase and Phospho-Protein Kinase B Signaling Pathways plus Activity of Macrophage-Stimulating Protein Contribute to the Protective Effect of Stachydrine on Acetaminophen-Induced Liver Injury.

Stachydrine, a prominent bioactive alkaloid derived from Leonurus heterophyllus, is a significant herb in traditional medicine. It has been noted for its anti-inflammatory and antioxidant characteristics. Consequently, we conducted a study of its hepatoprotective effect and the fundamental mechanisms involved in acetaminophen (APAP)-induced liver injury, utilizing a mouse model. Mice were intraperitoneally administered a hepatotoxic dose of APAP (300 mg/kg). Thirty minutes after APAP administration, mice were treated with different concentrations of stachydrine (0, 2.5, 5, and 10 mg/kg). Animals were sacrificed 16 h after APAP injection for serum and liver tissue assays. APAP overdose significantly elevated the serum alanine transferase levels, hepatic pro-inflammatory cytokines, malondialdehyde activity, phospho-extracellular signal-regulated kinase (ERK), phospho-protein kinase B (AKT), and macrophage-stimulating protein expression. Stachydrine treatment significantly decreased these parameters in mice with APAP-induced liver damage. Our results suggest that stachydrine may be a promising beneficial target in the prevention of APAP-induced liver damage through attenuation of the inflammatory response, inhibition of the ERK and AKT pathways, and expression of macrophage-stimulating proteins.

Effects of pre-weaning supplementation with fennel seed powder in two terms on growth performance, health status, and blood metabolites of Holstein dairy calves

This study investigated the effects of fennel seed powder (FSP) supplementation in liquid feed on growth performance, health, and blood parameters of preweaning dairy calves. In a 2 × 2 factorial design, 56 one-day-old female Holstein calves (n = 14/treatment) received liquid diet [colostrum (4.5 kg/d for the first 2 d), waste milk (6 kg/d from d 3 to 43, 5 kg/d from d 44 to 45, 4 kg/d from d 46 to 47, 3 kg/d from d 48 to 49)] supplemented with either of 3 or 6 g FSP (FSP3 or FSP6) in two terms (T: 25 or 50 d). Biometric and health traits were recorded daily, and blood metabolites were analyzed at d 25 and 50. The experiment was conducted under mild heat stress. The FSP6 group showed significant increase in starter dry matter intake (g/d and % of BW), starter crude protein (g/d), starter ether extract (g/d), starter ME (Mcal/d), total dry matter intake (g/d and % of BW), and total crude protein intake (g/d) during the last ten days of the experiment. The FSP6 group also had a significantly higher average daily gain (g/d), overall body weight (d 1–51), final weight (d 51), and total hip width compared with the FSP3 group. Feed conversion was higher in the FSP6–25 T or − 50 T groups than in the FSP3–25 T (but not −50 T) group. Calves receiving 3 g of FSP had a higher likelihood of experiencing elevated rectal temperature [≥ 39.4 ºC, odds ratio (OR) = 1.583 and confidence interval (CI) = 1.25 to 2.00], poor general appearance [(1 = normal and alert; 2 = ears drooped; 3 = head and ears drooped, dull eyes, slightly lethargic; 4 = head and ears drooped, dull eyes, lethargic; and 5 = severely lethargic); ≥ 2, OR = 1.47 and CI = 1.14 to 1.91)], and diarrhea [(1 = normal; 2 = soft to loose; 3 = loose to watery; 4 = watery, mucous, slightly bloody; and 5 = watery, mucous, and bloody); ≥ 3 (OR = 1.36 and CI = 1.04 to 1.76)] compared to those in the FSP6 group. Conversely, calves in the FSP6 group had fewer days of increased rectal temperature (4.75 vs. 7.11 d), poor general appearance (3.93 vs. 5.75 d), and diarrhea (3.85 vs. 5.11 d) than those in the FSP3 group. In addition, serum levels of alanine transferase (15.90 vs. 16.98 U/L for FSP6 vs. FSP3) and malondialdehyde (1.24 vs. 1.43 nmol/mL for FSP6 vs. FSP3) were significantly lower in the FSP6 group than in the FSP3 group. In addition, longer feeding of FSP was more effective than shorter feeding in lowering both traits. A triglyceride-lowering effect was observed in the FSP3 group compared with the FSP6 group (27.45 vs. 30.90 mg/dL). Overall, supplementation of liquid feed with 6 g FSP for 25 or 50 d improved growth performance in dairy calves.

Acute toxicity and therapeutic application of Zizyphus lotus and Ruta chalepensis phenolic extracts in treatment of gastroenteritis induced by Salmonella enterica subsp. arizonae

This study aimed to evaluate the antigastroenteritis effect against Salmonella enterica subsp. arizonae after therapeutic application of hydromethanolic extracts (MeOH.E) and aqueous extracts (Aq.E) of Zizyphus lotus (ZL) and Ruta chalepensis (RC). Acute oral toxicity was elucidated using in vivo methods and antigastroenteritis effect were evaluated using S. enterica subsp. arizonae-induced diarrheal model. Furthermore, test groups were treated with 400 mg/kg of the MeOH.E and Aq.E of each plant, while the control group was given neomycin (200 mg/kg) as standard antibiotic treatment, positive and negative controls were given the infectious germ (4 × 106 cells/mL) and 0.9% saline solution NaCl (10 ml/kg), respectively. Both plants extracts showed no toxicity for all the animals, so the LD50 was found to be greater than 5000 mg/kg. Moreover, an important bactericidal effect, using both plants extracts was determined against S. enterica subsp. arizonae cells in the intestine. In parallel, a decrease in alkaline phosphatase, amino alanine transferase and aspartate aminotransferase levels was observed with reduction in blood erythrocyte sedimentation rate in all treated animals. Thus, these results could be exploited in the medical field for the formulation of potent antibacterial drugs that cure severe gastrointestinal infections.

Garlic essential oil confers shielding against nephrotoxicity elicited by lead nitrate in Swiss albino mice

Lead is an immensely poisonous metal that can infiltrate the human body through various natural processes and human activities, therefore it possesses a significant risk to human health. Garlic (Allium sativum), a widely recognized medicinal plant, is employed to diminish a diverse array of health issues. While investigating the potential curative properties of the garlic essential oil (GEO) derived from fresh garlic bulbs, researchers explored its impact on the mice renal tissue subjected to lead nitrate. In the present research work, a sum of 36 healthy male Swiss albino mice were randomized into one control group (I) and five treatment groups: lead nitrate (II a), lead nitrate + low dose of GEO (II b), lead nitrate + high dose of GEO (II c), lead nitrate + silymarin (II d) and lead nitrate + vehicle olive oil (II e). Lead nitrate exposure resulted in elevated levels of alanine transferase (ALT), aspartate aminotransferase (AST), lipid peroxidation (LPO) and decreased levels of antioxidant enzymes, thus contributing to the oxidative stress and adversely affected the normal structure of renal tissues. Conversely, treatment with garlic essential oil (GEO) resulted in upsurge in these antioxidant levels and depletion in ALT, AST, and LPO levels. The findings support the notion that a higher dosage of garlic essential oil is more effective in mitigating lead nitrate-induced nephrotoxicity than a lower dosage. Consequently, garlic essential oil holds promise as a novel therapeutic agent for alleviating nephrotoxicity induced by lead nitrate exposure.

Alanine transferase levels (ALT) and triglyceride-glucose index are risk factors for type 2 diabetes mellitus in obese patients

AimsThe role of liver steatosis and increased liver enzymes (ALT) in increasing incident type 2 diabetes mellitus (T2DM) is debated, because of their differential effects on different ethnicities and populations. The aim of this study was to evaluate the role of elevated ALT in the development of T2DM in non-diabetic obese subjects receiving routine medical treatment.MethodsA total of 1005 subjects [296 men and 709 women, aged 45.7 ± 13.12 years, body mass index (BMI) 39.5 ± 4.86 kg/m2] were followed for a mean period of 14.3 ± 4.44 years. Subjects were evaluated for several metabolic variables, including the triglyceride-glucose index and the presence of metabolic syndrome (IDF 2005 definition), and were subdivided into ALT quartiles.ResultsT2DM developed in 136 subjects, and the difference was significant between the first and the fourth ALT quartile (p = 0.048). Both at univariate analysis and at stepwise regression, ALT quartiles were associated with incident T2DM. Traditional risk factors for T2DM coexisted, with a somehow greater predictive value, such as triglyceride-glucose index, age, arterial hypertension, LDL-cholesterol, and metabolic syndrome.ConclusionsThese data suggest an association between elevated ALT levels and the risk of incident T2DM in obesity.

BrdU does not induce hepatocellular damage in experimental Wistar rats

Bromodeoxyuridine (BrdU) is used in studies related to cell proliferation and neurogenesis. The multiple intraperitoneal injections of this molecule could favor liver function profile changes. In this study, we evaluate the systemic and hepatocellular impact of BrdU in male adult Wistar rats in 30 %-partial hepatectomy (PHx) model. The rats received BrdU 50 mg/Kg by intraperitoneal injection at 0.5, 1, 2, 3, 6, 9 and 16 days after 30 %-PH. The rats were distributed into four groups as follows, control, sham, PHx/BrdU(-) and PHx/BrdU(+). On day 16, we evaluated hepatocellular nuclei and analyzed histopathological features by haematoxylin-eosin stain and apoptotic profile was qualified by caspase-3 presence. The systemic effect was evaluated by liver markers such as alanine transferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (AP), bilirubin, total proteins and serum albumin content. The statistical analysis consisted of a student t-test and one-way ANOVA. BrdU did not induce apoptosis or hepatocellular damage in male rats. Multiple administrations of BrdU in male rats did not induce significant decrease body weight, but increased serum ALT and LDH levels were found. Our results show that the BrdU does not produce hepatocellular damage.

Gracilaria chorda subcritical water ameliorates hepatic lipid accumulation and regulates glucose homeostasis in a hepatic steatosis cell model and obese C57BL/6J mice

Ethnopharmacological relevanceRed seaweed, known as Rhodophyta, has a long history of use in traditional Asian medicine, including Traditional Chinese Medicine and Ayurveda. It is believed to have cooling and detoxification properties. Red seaweed species, such as Gracilaria, have been used in traditional remedies to address various conditions, such as inflammation, thyroid disorders, and digestive issues. Aim of the studyObesity is a risk factor of hepatic steatosis, a hallmark of non-alcoholic fatty liver disease (NAFLD) that affects nearly 25% of the worldwide population. Gracilaria chorda (GC) contains bioactive peptides that may be applicable in the prevention of metabolic syndrome diseases. This study investigated the effects of GC subcritical water extract at 210 °C (GCSW210) on preventing liver injury and lipid and glucose dysregulation in an oleic acid (OA)-induced hepatic steatosis cell model (HepG2) and high-fat diet (HFD)-induced obese animal model (C57BL/6J mice). Materials and methodsHuman hepatoma HepG2 cells were exposed to 0.1 mM OA for 24 h to induce hepatic steatosis and C57BL/6J mice were fed a HFD for 13 weeks. For lipid accumulation, triglyceride (TG) content was measured in both models, along with free fatty acid (FFA), plasma glucose, and insulin levels in HFD-fed mice. Protein expression of master regulators of adipogenesis and lipogenesis, as well as cholesterol and mitochondrial biosynthesis, was studied via western blotting in hepatic steatosis-induced in vitro and in vivo models. In addition, protein expression of the insulin signaling cascade in skeletal muscle tissues of HFD-fed mice was studied. ResultsGCSW210 significantly decreased lipid accumulation in HepG2 cells exposed to OA and suppressed the expression of lipogenic factors, such as sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase. In addition, GCSW210 abrogated transcription factors related to cholesterol biosynthesis, such as SREBP-2 and low-density lipoprotein receptor. Similarly, FFA, TG, serum glutamic acid, aspartate transaminase, alanine transferase, plasma glucose, and insulin levels were also significantly reduced in GCSW210-treated HFD-fed mice, which were comparable to the positive control mice treated with Garcinia cambogia extract. Additionally, GCSW210 enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase in the hepatic tissues of HFD-fed mice. Moreover, GCSW210 treatment improved insulin signal transduction by reducing insulin receptor substrate 1 Ser307 phosphorylation and elevated phosphatidylinositol 3-kinase/protein kinase B and glucose transporter type 4 protein expression in muscle tissue. 5-Hdroxymethylfufural (5-HMF) was confirmed to be active substances isolated from GCSW210 through LC-PDA and LC-MS. ConclusionsGCSW210 significantly regulated glucose metabolism, alleviated insulin resistance (IR) induced by high fatty acid synthesis and lipid accumulation, and elevated de novo lipogenesis by activating AMPK phosphorylation in both the liver and muscle tissues of HFD-fed mice. GCSW210 may be a potential functional food for preventing HFD-induced metabolic diseases, such as IR, NAFLD, and type 2 diabetes mellitus.

The alleviative efficacy of sildenafil and chrysin against zinc oxide nanoparticles-provoked hepatic and blood toxicity: role of MyD88/NF-κB1/TNF-α pathway

BackgroundZinc oxide nanoparticles are nanoparticles of metal oxide with semiconductor properties and proved many noxious effects on the mammalian cell. Sildenafil, a phosphodiesterase inhibitor, and chrysin, one of the flavonoids, proved to have anti-inflammatory and anti-oxidative stress effects.Methods48 rats were grouped into 8 groups equally. 1. (Control group) received normal diet and NaOH was added to water, 2. (chrysin group): 250 mg/kg, orally for 10 days, 3. (sildenafil group): 40 mg/kg, orally for 14 days, 4. (ZnO-NPs group): 200 mg/kg, intraperitoneal for 10 days, 5. (ZnO-NPs + chrysin as a prophylactic agent): given in the same previous doses and durations consecutively, 6. (ZnO-NPs + chrysin as a curative agent): given in the same previous doses and durations with chrysin given after ZnO-NPs administration for 10 days, 7. (ZnO-NPs + sildenafil as a curative agent): given in the same previous doses and durations with sildenafil given after ZnO-NPs administration for 10 days, and 8. (Combined treatment group chrysin + sildenafil) as combined treatment were given in the same previous doses and durations after ZnO-NPs administration for 10 days. Blood and samples from tissues were withdrawn for histopathological, biochemical studies, and comet assay at the end of the experiment.ResultsSildenafil and chrysin proved to protect from hepatotoxicity and hematotoxicity induced by zinc oxide nanoparticles as they lessened aspartate transaminase, alanine transferase, and alkaline phosphatase levels. They also reduced the oxidative stress enzyme levels. Gene expression of myeloid differentiation factor 88, nuclear factor kappa B1, tumor necrosis factor, and DNA damage decreased with treatment. Also, there was an improvement in the histopathological picture of the liver seen with treatment. Concurrent administration of sildenafil and chrysin revealed much better improvement than either drug used alone.ConclusionChrysin and sildenafil have ameliorative effects against ZnO-NPs-induced hepatotoxicity and hematotoxicity, their protective effect is either preventive with chrysin or curative with chrysin and sildenafil.

N-acetylcysteine in the Donor, Recipient, or Both Donor and Recipient in Liver Transplantation: A Systematic Review With Meta-analysis and Trial Sequential Analysis.

N-acetylcysteine (NAC) is a potentially effective drug for treating ischemia-reperfusion injury in transplanted livers, but its effect remains controversial. A systematic review and meta-analysis of relevant clinical trials published and registered in the Cochrane Library, MEDLINE, EMBASE, ClinicalTrial.gov, WHO ICTRP, etc, before March 20, 2022 were conducted and registered with PROSPERO (CRD42022315996). Data were pooled using a random effects model or a fixed effects model based on the amount of heterogeneity. Thirteen studies with 1121 participants, 550 of whom received NAC, were included. Compared with the control, NAC significantly reduced the incidence of primary graft nonfunction (relative risk [RR], 0.27; 95% confidence interval [CI], 0.08-0.96), the incidence of postoperative complications (RR, 0.52; 95% CI, 0.41-0.67), the peak postoperative aspartate transferase level (mean difference [MD], -267.52; 95% CI, -345.35 to -189.68), and the peak alanine transferase level (MD, -293.29; 95% CI, -370.39 to -216.20). NAC also improved 2-y (RR, 1.18; 95% CI, 1.01-1.38) graft survival rate. However, NAC increased the intraoperative cryoprecipitate (MD, 0.94; 95% CI, 0.42-1.46) and red blood cell (MD, 0.67; 95% CI, 0.15-1.19) requirements. Moreover, NAC was administered in various modes in these studies, including to the donor, recipient, or both. Subgroup analysis and network meta-analysis showed that NAC administration to recipients could play a more significant role than the other 2 administration modes. Our study supports the protective effect of NAC against LT-induced ischemia-reperfusion injury and shows better clinical outcomes of NAC administration to recipients.

Donor safety of remnant liver volumes of less than 30% in living donor liver transplantation: A systematic review and meta-analysis.

This meta-analysis aimed to investigate the acceptability of donor remnant liver volume (RLV) to total liver volume (TLV) ratio (RLV/TLV) being <30% as safe in living donor liver transplantations (LDLTs). Online databases were searched from January 2000 to June 2022. Pooled odds ratios (ORs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects model. One prospective and seven retrospective studies comprising 1935 patients (164 RLV/TLV <30% vs. 1771 RLV/TLV ≥30%) were included. Overall (OR=1.82; 95% CI [1.24, 2.67]; p=.002) and minor (OR=1.88; 95% CI [1.23, 2.88]; p=.004) morbidities were significantly lower in the RLV/TLV ≥30% group than in the RLV/TLV <30% group (OR=1.82; 95% CI [1.24, 2.67]; p=.002). No significant differences were noted in the major morbidity, biliary complications, and hepatic dysfunction. Peak levels of bilirubin (SMD=.50; 95% CI [.07, .93]; p=.02) and international normalized ratio (SMD=.68; 95% CI [.04, 1.32]; p=.04) were significantly lower in the RLV/TLV≥30% group than in the RLV/TLV <30% group. No significant differences were noted in the peak alanine transferase and aspartate transaminase levels and hospital stay. Considering the safety of the donor as the top priority, the eligibility of a potential liver donor in LDLT whose RLV/TLV is expected to be <30% should not be accepted.

Incidence, risk factors and outcomes of checkpoint inhibitor-induced liver injury: A 10-year real-world retrospective cohort study

Background & AimsCheckpoint inhibitors (CPI) account for increasing numbers of drug-induced liver injury (DILI) cases. We aimed to determine the incidence rate and risk factors associated with checkpoint inhibitor-induced liver injury (ChILI). MethodsPrescription event monitoring was performed on all melanoma and renal cancer patients who received CPI at a tertiary centre between 2011 and 2021. ChILI cases were identified using the definitions, grading, and causality assessment methods validated for DILI. We assessed risk factors associated with ChILI in CPI-naive patients using multivariable logistic regression model. Consecutive patients with suspected ChILI from two other tertiary centres were adjudicated and combined for case characterisation and outcomes of ChILI. ResultsOut of 432 patients who received CPI over 10 years, ChILI occurred in 38 (8.8%) with an overall incidence rate of 11.5 per 1,000 person-months (95% CI 8.2–15.8). Probability of ChILI was highest in combination therapy (32%) and no new events occurred beyond 135 days of treatment. Risk factor analysis showed that combination therapy, female sex, higher baseline alanine transferase level and lower baseline alkaline phosphatase level were independently associated with higher risk of ChILI. In total, 99 patients were adjudicated to have ChILI from three centres. Although Common Terminology Criteria for Adverse Events classified 20 patients (20.2%) to have ‘life-threatening’ grade 4 hepatitis, ChILI severity was graded as mild in 45 (45.5%) and moderate in the remaining 54 (54.5%) cases. ConclusionsThe real-world risk of ChILI is higher than previously reported. Among patients receiving dual CPI, this risk falls markedly after 4.5 months. As Common Terminology Criteria for Adverse Events overestimates its clinical severity, case-definition, evaluation and management of ChILI should be revised to harmonise care. Impact and implicationsUsing prescription event monitoring over a 10-year period, the incidence rate of checkpoint inhibitor induced liver injury (ChILI) based on established case definitions for drug-induced liver injury (DILI) is 11.5 per 1,000 person-months. Formal causality assessment identified an alternative cause in 19% of patients with suspected ChILI highlighting the importance of systematic evaluation by clinicians to minimise unnecessary immunosuppression. Intensity of monitoring in patients receiving combination therapy regime after 4.5 months of therapy can be reduced as the risk of new onset ChILI beyond this point is minimal. Current Common Terminology Criteria for Adverse Events (CTCAE) grading overestimates clinical severity of ChILI and hence contributes to avoidable hospitalisation.

Associations between per- and polyfluoroalkyl substances, liver function, and daily alcohol consumption in a sample of U.S. adults

Background and aimPer- and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment and in the serum of the U.S. population. We sought to evaluate the association of PFAS independently and jointly with alcohol intake on liver function biomarkers in a sample of the U.S. general population. MethodsUsing data from the National Health and Nutrition Examination Survey (2003–2016; N = 11,794), we examined the five most historically prevalent PFAS with >75% detection rates. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between PFAS (quartiles and log-transformed continuous, ng/mL) and high levels (>95th percentile) of liver injury biomarkers using logistic regression models adjusted for key confounders. We evaluated interactions between PFAS and alcohol consumption and sex via stratified analyses and conducted sub-analyses adjusting for daily alcohol intake among those with available drinking history (N = 10,316). ResultSerum perfluorooctanoic acid (PFOA) was positively associated with high levels of alanine transferase (ALT) without monotonic trend (ORQ4vsQ1 = 1.45, CI: 0.99-2.12; p-trend = 0.18), and with increased aspartate transaminase when modeled continuously (OR = 1.15, CI: 1.02–1.30; p-trend = 0.03). Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were both inversely associated with alkaline phosphatase while a trend was evident only for PFHxS (p = 0.02). A non-monotonic inverse association was observed with PFOA (p-trend = 0.10). The highest quartile of PFOS was associated with high total bilirubin (TB; ORQ4vsQ1 = 1.57, CI: 1.01–2.43, p-trend = 0.02). No significant associations were found between any PFAS and γ-glutamyl transpeptidase. We found no associations for perfluorodecanoic acid and perfluorononanoic acid. We observed some suggestive interactions with alcohol intake, particularly among heavy drinkers. ConclusionConsistent with other studies, serum levels of PFOA, PFHxS and PFNA were positively associated with high levels of ALT, and we also observed weak positive associations between some PFAS and TB. Associations observed among heavy drinkers warrant additional evaluation.

Post-thrombolysis early neurological deterioration occurs with or without hemorrhagic transformation in acute cerebral infarction: risk factors, prediction model and prognosis

ObjectivesEarly neurological deterioration (END) after ischemic stroke is a severe clinical event and can be caused by hemorrhagic and ischemic injury. We studied the difference between the risk factors of END occurs with or without hemorrhagic transformation after intravenous thrombolysis. Materials and methodsConsecutive cerebral infarction patients who underwent intravenous thrombolysis from 2017 to 2020 in our hospital were retrospectively recruited. END was defined as a ≥2 points increase on 24-h National Institutes of Health Stroke Scale (NIHSS) score after therapy compared with the best neurological status after thrombolysis and divided into two types based on the computed tomography (CT): symptomatic intracranial hemorrhage (ENDh) and non-hemorrhagic factors (ENDn). Potential risk factors of ENDh and ENDn were assessed by multiple logistic regression and applied to establish the prediction model. ResultsA total of 195 patients were included. In multivariate analysis, the previous history of cerebral infarction (odds ratio [OR],15.19; 95% confidence interval [CI],1.43–161.17; P = 0.025), previous history of atrial fibrillation (OR,8.43; 95%CI,1.09–65.44; P = 0.043), higher baseline NIHSS score (OR,1.19; 95%CI,1.03–1.39; P = 0.022) and higher alanine transferase level (OR,1.05; 95%CI, 1.01–1.10; P = 0.016) were independently associated with ENDh. While higher systolic blood pressure (OR,1.03; 95%CI,1.01–1.05; P = 0.004), higher baseline NIHSS score (OR,1.13; 95%CI,2.86–27.43; P < 0.000) and large artery occlusion (OR,8.85, 95%CI,2.86–27.43; P < 0.000) were independent risk factors of ENDn. The prediction model showed good specificity and sensitivity in predicting the risk of ENDn. ConclusionsThere are differences between the major contributors to ENDh and ENDn, while a severe stroke can increase the occurrence of both sides.