Liver Function Parameters Research Articles

Altered Liver Enzyme Markers in Patients with Asymptomatic, and Mild Omicron Infection: A Retrospective Study.

The emergence of the SARS-CoV-2 Omicron variant has posed a significant global public health challenge. Elucidating the laboratory profiles of individuals infected with this variant is crucial for assessing organ damage. This study aimed to investigate the variations in liver function tests and their correlation with demographic characteristics and inflammatory markers in patients with early Omicron variant infections. A retrospective cohort study was conducted on 1133 mild or asymptomatic COVID-19 cases at Tianjin First Central Hospital. Data on age, gender, body mass index (BMI), and serum markers were collected and analyzed. Statistical analyses were performed using SPSS software, version 24.0. Abnormal liver function parameters, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (TBIL), were observed in 314 (27.71%) patients. "Hepatocellular type" was identified in 56 (4.94%) patients, "cholestatic type" in 185 (16.33%) patients, and "mixed type" in 73 (6.44%) patients. In the mixed group, we observed a pronounced elevation in the levels of ALT, AST, and GGT. Moreover, the hepatocellular group exhibited a statistically significant increase in AST and ALT concentrations relative to both the normal and cholestatic groups. Notably, the cholestatic group demonstrated a substantial increment in ALP levels. Males had a significantly higher prevalence of "abnormal liver enzyme markers" compared to females. Patients with "abnormal liver enzyme markers" exhibited significantly decreased immunoglobulin G (IgG) levels and elevated levels of inflammatory markers, including procalcitonin (PCT), interleukin-6 (IL6), as well as C-reactive protein (CRP) compared to normal group. Logistic regression analysis revealed that male gender and PCT levels were significantly associated with the risk of abnormal liver enzyme markers. Patients in hepatocellular group were likely accompanied with high CRP levels, whereas those in the cholestatic type were associated with high IL6 levels. Early Omicron infection might cause liver stress response. Elevated liver enzyme marker levels were correlated with age, gender, inflammatory factors, and IgG.

AMELIORATION OF LIVER AND KIDNEY FUNCTION PARAMETERS IN ALLOXAN-INDUCED DIABETIC RATS TREATED WITH 3-[2-(1,5-Dimethyl-3-oxo-2-Phenyl-2,3-Dihydro- 1H-Pyrazol-4-yl) Hydrazinylidene]-1-Phenylbutanedione, and its Ni(II) Complex.

This hydrazone: 3-[2-(1,5-Dimethyl-3-oxo-2-Phenyl-2,3-Dihydro-1H-Pyrazol-4-yl) Hydrazinylidene]-1-Phenylbutanedione (HL), and its Ni (II) Complex ([Ni(HL)2]Cl2) have been reported to possess hypoglycaemic property but the effects of their use on kidney and liver functions in diabetic animals have not been investigated. The study investigated some biochemical parameters in the liver and kidney of alloxan-induced diabetic rats treated with these hydrazone compounds. Diabetes was induced by a single intraperitoneal dose of alloxan (150 mg/kg). Data showed that these compounds induced a significant decrease in serum glucose levels in the diabetic rats. Diabetic rats were administered orally with compounds for fourteen days after which some biochemical indices in the serum, liver and kidney were measured and compared with the control. Serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, total protein and creatinine of untreated diabetic group was significantly elevated when compared with the normal control group. The ALP, AST concentrations of diabetic rats treated with low and high doses of HL was observed to be non-significantly (p > 0.05) higher compared with rats in the normal control group A. A significantly (p < 0.05) decrease in the ALT, AST and ALP concentrations of diabetic rats treated with 200 and 400 mg/kg b.w. of HL and [Ni(HL)2]Cl2 were observed when compared with untreated rats in group B. These results suggest that administration of these compounds to diabetic rats did not have any adverse effect on the liver and kidney functions in rats showing that the compounds are not toxic to man.

Comparison of serum alkaline phosphatase levels between two measurement methods in chronic hemodialysis patients in Japan: involvement of ABO blood group system and relationship with mortality risk.

Elevated serum alkaline phosphatase (ALP) levels are a risk factor for all-cause mortality in hemodialysis patients. Traditionally in Japan, ALP measurements were conducted using the JSCC method, which yields higher ALP measurement values than the IFCC method, mainly due to its increased sensitivity to intestinal ALP. Serum total ALP levels before and after switching the assay method from JSCC to IFCC were compared among different blood types in 521 hemodialysis patients (Study 1). The association between ALP levels measured by the JSCC method and 7-year mortality was analyzed, including blood types and liver function parameters as covariates, in 510 hemodialysis patients (Study 2). ALP levels measured by the JSCC method were approximately three times higher than those measured by the IFCC method, with significant elevation in patients with blood types B and O compared to those with blood types A and AB. Similarly, ALP levels measured by the IFCC method were significantly higher in patients with blood types B and O compared to those with blood types A and AB (Study 1). The highest tertile of ALP levels showed a significantly increased risk of all-cause mortality, even after adjusting for patient background. However, this significance disappeared when serum liver function-related or inflammatory markers were included as covariates (Study 2). ALP levels measured by the JSCC method are associated with life prognosis, but caution should be exercised due to their elevation in patients with blood types B and O and in those with hepatic dysfunction or inflammation.

Effects of Probiotics on Liver and Kidney Function Parameters

This study aimed to study the effects of probiotics on liver and kidney function parameters. An in vitro study was used to identify food-grade probiotics for human consumption. As far as probiotic strains used, B. longum subspecies infantis, L. acidophilus, as well as B. bifidum are all GRAS (Generally Recognized as Safe). Over the course of six months, 100 patients with CKD and Liver disease 50 patients were without treatment and 50 patients were given two capsules each morning and evening containing 2.5*109 CFU B. longum subspecies infantis, L. acidophilus, as well as B. bifidum at a ratio of 1:1:1, and 50 normal indivisuals were used in this study. Pre-test nutritionists recommended the participants to eat low-protein diets and to avoid any lifestyle or dietary changes throughout the experiment time. Blood was collected for evaluation of AST, ALT, Total protein, Urea, and creatinine levels in both patients and normal. These kits were obtained from Biolabo company, these were done according to company instructions. The results showed that the probiotics had a therapeutics effect which causes a significant difference in all parameters in treated patients as compared with patients that were not treated. In conclusion, Probiotics have therapeutic effects on the injured kidney and the liver, which are indicated by decreasing the liver and kidney functions.

Risk of low levels of blood group antibodies mediating hemolysis in ABO-incompatible neonates with negative three hemolysis tests.

To explore the risk of low-level blood group antibody-mediated hemolysis in ABO-incompatible newborns with negative three hemolysis tests, aiming to assist in the identification and management of neonatal jaundice. A retrospective case-control study was performed in 892 children with jaundice. The patients were divided into three groups: group I, ABO compatible, negative three hemolysis tests; group II, ABO incompatible, negative three hemolysis tests; and group III, ABO incompatible, positive three hemolysis tests. We analyzed the differences in clinical data, blood routine and biochemical laboratory results. (1) Patients in group II had higher levels of mean corpuscular volume (MCV), standard deviation of red blood cell volume distribution width (RDW-SD), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and bile acid (BA) than those in group I (P < 0.05). However, there were no statistically significant differences in the MCV, ALT, ALP and BA levels between groups II and III (P > 0.05). (2) Mean corpuscular hemoglobin concentration (MCHC) >359.5 g/L, cell volume distribution width (RDW-CV) >15.95%, and reticulocyte count (RET) >4.235% were identified as independent predictors of positive hemolysis test results (P < 0.001). The combination of MCHC, RDW-CV, and RET% yielded an AUC of 0.841. Low-level blood group antibody-mediated hemolysis may occur in ABO-incompatible neonates even when three hemolysis tests are negative. Changes in liver function parameters must be monitored. The combination of MCHC, RDW-CV, and RET% can be used to improve the detection rate of HDN.

Porto-sinusoidal vascular liver disorder with portal hypertension: Natural history and long-term outcome

Current knowledge of the natural history of patients with porto-sinusoidal vascular disorder (PSVD) is derived from small studies. The aim of the present study was to determine the natural history of PSVD and prognostic factors in a large multicenter cohort of patients. We performed a retrospective study on patients with PSVD and signs of portal hypertension (PH) prospectively registered in 27 centers. A total of 587 patients were included, median age of 47 years and 38% were women. Four-hundred and one patients had an associated condition, which was graded as severe in 157. Median follow-up was 68 months. At diagnosis, 64% of patients were asymptomatic while 36% had a PH-related complication: PH-related bleeding in 112 patients, ascites in 117, and hepatic encephalopathy in 11. In those not presenting with bleeding, the incidence of first bleeding was 15% at 5 years, with a 5-year rebleeding rate of 18%. The 5-year cumulative incidence of new or worsening ascites was 18% and of developing PVT was 16%. Fifty (8.5%) patients received a liver transplantation and 109 (19%) died, including 55 non-liver-related deaths. Transplant-free survival was 97% and 83% at 1 and 5 years, respectively. Variables independently associated with transplant-free survival were age, ascites, serum bilirubin, albumin and creatinine levels at diagnosis and severe associated conditions. This allowed for the creation of a nomogram that accurately predicted prognosis. The prognosis of PSVD is strongly determined by the severity of the associated underlying conditions and parameters of liver and renal function. Porto-sinusoidal vascular liver disorder (PSVD) is a rare entity that usually affects young people, frequently causes severe complications of portal hypertension, and may reduce life expectancy. To date, there is scarce information regarding its clinical manifestations, natural history and prognostic factors. The present study, including the largest number of patients with PSVD reported so far, shows that overall, when managed at centers of expertise, the prognosis of patients with PSVD is good, with LT-free survival rates of 83% and 72% at 5 and 10 years, respectively. Presence and severity of an underlying associated condition, presence of ascites, age and bilirubin, albumin and creatinine levels were associated with poor prognosis. These results are important to know for hepatologists. A final model combining these parameters enabled development of a nomogram that predicts prognosis with good discrimination and calibration capacity and can be easily applied in clinical practice.

Improvement of Laboratory Hepatic Parameters After Treatment With 177 Lu-DOTATATE : Cohort in an Oncology Reference Center.

Well-differentiated neuroendocrine neoplasms (NETs) overexpress the somatostatin receptor, which is the target for the peptide receptor radionuclide therapy (PRRT). NETs have a slow growth rate and can metastasize to liver, bone, and lungs. In NETs patients, liver metastasis is an important prognostic marker because liver failure is one of the most common causes of death in this population. In this regard, we aimed to describe the changes in laboratorial parameters in patients submitted to PRRT with 177 Lu-DOTATATE, focusing on hepatic parameters. One hundred ten patients treated with 1 to 4 cycles of 7.4 GBq (200 mCi) of 177 Lu-DOTATATE from January 2011 to December 2021 were analyzed in this retrospective observational single-center study. Patients were submitted to blood tests before and after each cycle of PRRT. Laboratory measurements were collected to assess liver function, cholestasis, kidney, and bone marrow function. In the general population (n = 110), ALP ( P = 0.013) and GGT ( P < 0.001) showed a statistically significant reduction. Patients with high liver disease volume showed a statistically significant reduction in ALT ( P = 0.016), whereas patients with low liver disease volume showed a statistically significant reduction in GGT ( P = 0.013). All parameters for bone marrow function showed a statistically significant decrease in all population subsets. Patients treated with 177 Lu-DOTATATE showed a significant improvement in liver function and cholestasis parameters, and a consistent decrease in bone marrow function, even in the presence of advanced liver disease.

Evaluation of diagnostic potential of maternal serum ischemia modified albumin in cases of pre-eclampsia.

The underlying causes and mechanisms of pre-eclampsia (PE), its exact etiology remains unclear and poorly understood. Hypoxia, ischemia, and oxidative stress induced by free radicals have been associated with development of PE. Ischemia-modified albumin (IMA) is a chemically modified albumin due to oxidative stress. IMA, a serum biomarker of hypoxia, ischemia, and oxidative free radicals is a potential biomarker for PE. The aim of the current proposal was to study serum IMA as a diagnostic biomarker of pre-eclampsia (PE) in pregnant females and to evaluate the correlation between serum IMA and different markers of pre-eclampsia (BP, urinary protein, LFT, KFT, serum total protein & uric acid). A total of 60 pregnant women aged between 21 and 35 years were recruited (30 PE cases and 30 normal pregnancy). Serum IMA was measured by spectrophotometric method developed by Bar-Or D. BP and biochemical parameters (urinary protein, LFT, KFT, serum total protein & uric acid) were also assayed and compared between two groups. Correlation analysis was done for analyzing the relationship between serum IMA and biochemical parameters. The mean serum IMA was significantly higher in normotensive pregnant females (0.93 ABSU) than PE cases (0.71 ABSU). Kidney function and liver function parameters were more deranged in PE cases than in controls. Serum IMA was positively correlated with serum creatinine (r=0.322), serum uric acid (r=0.54) and urinary protein (0.376) whereas negatively correlated with total serum bilirubin (r=-0.515) and serum albumin (r=-0.380). Elevated serum IMA concentrations in normotensive pregnant controls as compared to PE cases suggest that apart from ongoing ischemia and oxidative stress in placenta IMA values are influenced by many other mechanisms in pregnancy.

Comparative Evaluation of Diabetes Complication Using Liver Function Parameters as Indices between Male and Female Alloxan Induced Diabetic Rats

It is known that diabetes causes liver damage. On the other hand, because most cases of liver damage have been investigated in males, examining the relationship of this disease in both sexes is of great importance. This study was aimed at, comparatively evaluating diabetic complications using histopathological examination and liver function parameters as indices in alloxan-induced diabetic rats. A total of 24 male and female rats divided into four groups of six animals each were used for the experiment. Group A were female control, Group B were male control while group C and D were alloxan induced diabetic female and male rats respectively. Groups A and B were non diabetic rats fed with rat diet all through the experiment. Group C and D were diabetes induced with a single intraperitoneal injection of alloxan (120mg/kg). At the end of the inducement period, the rats were fasted overnight and sacrificed. Blood was collected by ocular puncture for the determination of fasting plasma glucose (FPG) and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), direct bilirubin (DB), total protein (TP) and albumin (ALB) using spectrophotometric method. Histology of the liver was determined by H and E technique. The results showed the experimental group C (365.83±43.6mg/dl) and D (368.94±43.93mg/dl) had significantly elevated levels of FPG when compared with the controls group A (116.00±9.11mg/dl) and B (108.33±5.5mg/dl) confirming the induction of diabetes (P=0.000). The liver of both male and female diabetic rats showed ballooning degeneration. In the males, these were arranged in normal sheets and cord around central vein in some areas of the center, on the other hand, the central vein of the female diabetic rats appears slightly enlarged containing blood clots and the arrangement of the hepatocytes in sheets or cords around the central vein was completely distorted. There was no significant difference (p&gt;0.05) in the mean serum levels of ALP, AST, ALT, DB, TP and ALB in female diabetics when compared to male diabetic rats. The mean serum level of TB was significantly reduced (p=0.004) in female diabetics (0.53±0.05) than in the male diabetic albino rats (0.69±0.09). This study showed the liver histology and function are variably altered in diabetes mellitus. Further research on the causes of liver damage will help us to unravel the pathogenesis of diabetes and its complications.

Population pharmacokinetics of tamsulosine in patients with benign prostatic hyperplasia.

The study aimed to determine the typical clearance and volume of distribution values of tamsulosin in patients with benign prostatic hyperplasia (BPH), and to identify factors with a measurable impact on the drug's elimination. This open-label, single-arm population pharmacokinetic study involved 65 adult men with BPH who had been on tamsulosin therapy for at least seven days. The steady-state serum concentrations of tamsulosin were measured using liquid chromatography-tandem quadrupole mass spectrometry. Population pharmacokinetic parameters, their variability, and influencing factors were estimated based on a two-compartment pharmacokinetic model using NONMEM software. The estimated tamsulosin clearance in BPH patients was 0.719L/h, and the steady-state volume of distribution was 32L. Neither renal nor liver function parameters had a statistically significant effect on tamsulosin clearance. However, a positive correlation was observed between hemoglobin levels and tamsulosin clearance in the BPH patient cohort. Our investigation reveals significant associations between tamsulosin pharmacokinetics and specific characteristics of patients with lower urinary tract symptoms (LUTS) due to BPH. The study highlights that tamsulosin clearance is associated with hemoglobin levels in patients with LUTS/BPH. This study underscores the importance of considering patient-specific factors when managing BPH treatment with tamsulosin, emphasizing associations rather than causative relationships.

Ocimum basilicum and Lagenaria siceraria Loaded Lignin Nanoparticles as Versatile Antioxidant, Immune Modulatory, Anti-Efflux, and Antimicrobial Agents for Combating Multidrug-Resistant Bacteria and Fungi.

Lignin nanoparticles emerged as a promising alternative for drug delivery systems owing to their biodegradability and bioactive properties. This study investigated the antimicrobial activity of the ethanolic extract of Ocimum basilicum-loaded lignin nanoparticles (OB-LNPs) and Lagenaria siceraria seed oil-loaded lignin nanoparticles (LS-LNPs) to find a solution for antimicrobial resistance. OB-LNPs and LS-LNPs were tested for their antimicrobial potential against Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus aureus, Salmonella enterica, Trichophyton mentagrophytes, Trichophyton rubrum, and Microsporum canis. OB-LNPs and LS-LNPs were further tested for their anti-efflux activity against ciprofloxacin-resistant Salmonella enterica strains and for treating Salmonella infection in a rat model. We also investigated the antifungal efficacy of OB-LNPs and LS-LNPs for treating T. rubrum infection in a guinea pig model. Both OB-LNPs and LS-LNPs showed strong antimicrobial potential against S. Typhimurium and T. rubrum infections. LS-LNPs showed antibacterial activity against Salmonella enterica species with a MIC range of 0.5-4 µg/mL and antifungal activity against T. rubrum with a MIC range of 0.125-1 µg/mL. OB-LNPs showed antibacterial activity against Salmonella enterica species with a MIC range of 0.5-2 µg/mL and antifungal activity against T. rubrum with a MIC range of 0.25-2 µg/mL. OB-LNPs and LS-LNPs downregulated the expression of ramA and acrB efflux pump genes (fold change values ranged from 0.2989 to 0.5434; 0.4601 to 0.4730 for ramA and 0.3842-0.6199; 0.5035-0.8351 for acrB). Oral administration of OB-LNPs and LS-LNPs in combination with ciprofloxacin had a significant effect on all blood parameters, as well as on liver and kidney function parameters. Oxidative stress mediators, total antioxidant capacity, and malondialdehyde were abolished by oral administration of OB-LNPs and LS-LNPs (0.5 mL/rat once daily for 5 days). Interferon-γ and tumor necrosis factor-α were also reduced in comparison with the positive control group and the ciprofloxacin-treated group. Histopathological examination of the liver and intestine of OB-LNPs and LS-LNPs-treated rats revealed an elevation in Salmonella clearance. Treatment of T. rubrum-infected guinea pigs with OB-LNPs and LS-LNPs topically in combination with itraconazole resulted in a reduction in lesion scores, microscopy, and culture results. In conclusion, OB-LNPs and LS-LNPs possess immunomodulatory and antioxidant potential and can be used as naturally derived nanoparticles for drug delivery and treatment of Salmonellosis and dermatophytosis infections.

Impact of dietary selenium and blood concentration on liver function: a population-based study.

Evidence on the association between selenium and liver function parameters is limited and controversial. Data on dietary selenium intake, blood selenium concentration, and liver function parameters were obtained from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. Associations between selenium (dietary intake and blood concentration) and liver function parameters [alanine aminotransferase (ALT), aspartate aminotransferase (AST), the ALT/AST ratio, gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP)] were assessed using multivariate linear regression models. Subgroup analyses and interaction tests were conducted to examine differences in associations according to age, gender, body mass index (BMI), diabetes, and physical activity. The study included 6,869 participants after screening. The multivariate linear regression model revealed that dietary selenium intake was positively associated with ALT (β = 0.112, 95% CI = 0.041, 0.183) and the ALT/AST ratio (β = 0.002, 95% CI = 0.001, 0.004) after adjustment for covariates. Results of blood selenium concentration also showed that higher blood selenium levels were positively associated with ALT (β = 0.436, 95% CI = 0.308, 0.564), AST (β = 0.112, 95% CI = 0.015, 0.208), and the ALT/AST ratio (β = 0.012, 95% CI = 0.009, 0.015). However, ALP decreased with increasing blood selenium concentration (β = -0.207, 95% CI = -0.414, -0.000). In addition, we found significant differences in the effect of selenium on liver function parameters according to age, gender, and BMI. Dietary selenium intake and blood concentration affect liver function parameters. These findings suggest that further research is needed to explore these associations to promote liver health and disease prevention.

Age, Gender, and BMI Modulate the Hepatotoxic Effects of Brominated Flame Retardant Exposure in US Adolescents and Adults: A Comprehensive Analysis of Liver Injury Biomarkers.

Brominated flame retardants (BFRs), commonly found in consumer products, have been identified as potential hazards to liver function. While the individual effects of specific BFRs are somewhat understood, there is limited evidence on how mixtures of these chemicals, especially when influenced by demographic factors, interact to affect liver function. This study utilized data from 10,828 participants aged 12 and above from the National Health and Nutrition Examination Survey (2005-2016) to investigate the associations between BFRs (both individually and in combinations) and biomarkers of liver injury. The study focused on how age, gender, and body mass index (BMI) modify modulate these effects. Multivariate linear regression, restricted cubic spline function, weighted quantile sum (WQS) regression, and quantile g-computation (qgcomp) models were used to analyze the linear, non-linear, and joint associations between BFR levels and liver function parameters. We found positive associations between the mixed BFRs index and AST, ALT, GGT, ALP, and TBIL levels and a negative association with ALB levels. PBDE28, PBDE47, and PBB153 consistently contributed to the top weight in both the WQS and qgcomp models. Most critically, the study demonstrated that the relationship between co-exposure to BFRs and liver function parameters was modified by age, gender, and BMI. Therefore, our study highlights the importance of considering demographic diversity in assessing the risk of BFR-induced liver damage and supports the implementation of tailored preventive and intervention strategies.

Superior cuproptotic efficacy of diethyldithiocarbamate-Cu4O3 nanoparticles over diethyldithiocarbamate-Cu2O nanoparticles in metastatic hepatocellular carcinoma.

Metastatic hepatocellular carcinoma (HC) is a serious health concern. The stemness of cancer stem cells (CSCs) is a key driver for HC tumorigenesis, apoptotic resistance, and metastasis, and functional mitochondria are critical for its maintenance. Cuproptosis is Cu-dependent non-apoptotic pathway (mitochondrial dysfunction) via inactivating mitochondrial enzymes (pyruvate dehydrogenase "PDH" and succinate dehydrogenase "SDH"). To effectively treat metastatic HC, it is necessary to induce selective cuproptosis (for halting cancer stemness genes) with selective oxidative imbalance (for increasing cell susceptibility to cuproptosis and inducing non-CSCs death). Herein, two types of Cu oxide nanoparticles (Cu4O3 "C(I + II)" NPs and Cu2O "C(I)" NPs) were used in combination with diethyldithiocarbamate (DD, an aldehyde dehydrogenase "ALDH" inhibitor) for comparative anti-HC investigation. DC(I + II) NPs exhibited higher cytotoxicity, mitochondrial membrane potential, and anti-migration impact than DC(I) NPs in the treated human HC cells (HepG2 and/or Huh7). Moreover, DC(I + II) NPs were more effective than DC(I) NPs in the treatment of HC mouse groups. This was mediated via higher selective accumulation of DC(I + II) NPs in only tumor tissues and oxidant activity, causing stronger selective inhibition of mitochondrial enzymes (PDH, SDH, and ALDH2) than DC(I)NPs. This effect resulted in more suppression of tumor and metastasis markers as well as stemness gene expressions in DC(I + II) NPs-treated HC mice. In addition, both nanocomplexes normalized liver function and hematological parameters. The computational analysis found that DC(I + II) showed higher binding affinity to most of the tested enzymes. Accordingly, DC(I + II) NPs represent a highly effective therapeutic formulation compared to DC(I) NPs for metastatic HC.

Effect of prolonged administration of ethanolic seed extract of Monodora myristica on some liver function enzymes and antioxidant status in rats

This study investigated the effect of prolonged consumption of ethanolic seed extract of Monodora myristica (ESEM)for 21 day on some liver function enzymes and antioxidant status in rats. Eighteen (18) male Wistar rats were randomly divided into three groups (n=6) and treated orally as follows: Group I: (Control) received 0.4 mL of 0.1 % vehicle (tween 80) for 21 consecutive days; Group II: (Low dose) and Group III (High dose) received 50 mg/kg and 100 mg/kg of ethanolic seed extract of Monodora myristica (ESEM) for 21 consecutive days respectively. The animals were sacrificed under anaesthesia (via ketamine; 90 mg/kg) 24 h after the last treatment. Blood and liver tissue samples were collected and processed for analysis of some liver function parameters and antioxidant status. The oral LD50 value of ESEM in rats exceeded 5000 mg/kg body weight, indicating a relatively low toxicity. ESEM administration for 21 days at doses of 50 mg/kg and 100 mg/kg significantly (p&lt;0.05) improved the serum levels of ALT (13.60±0.40 U/L; 12.42±0.42 U/L), AST (24.24±0.88 U/L; 21.19±0.90 U/L) and GGT (1.86±0.07 U/L; 1.15±0.08 U/L) compared to the normal control group (16.40±0.46 U/L; 28.46±0.94 U/L; 2.44±0.10 U/L) respectively. Normal level of SOD (9.24±0.12 U/mg protein) and CAT (1.74±0.04 µmol/min/mg protein) were significantly increased to 10.44±0.10 U/mg protein; 2.03±0.02 µmol/min/mg protein and 11.98±0.14 U/mg protein; 2.42±0.05 µmol/min/mg protein, in the animals that received 50 and 100 mg/kg of ESEM respectively. Also, the normal concentration of MDA (1.05±0.03 nmol/mg protein) was significantly (p&lt;0.05) attenuated to 0.82±0.04 and 0.65±0.02 nmol/mg protein, in the animals that received oral administration of ESEM at 50 mg/kg and 100 mg/kg respectively. The findings suggest that long-term use of ethanolic seed extract of Monodora myristica at low dose is unlikely to induce hepatotoxicity, but rather exerts hepatoprotective effects, enhancing the overall liver health. Keywords: Prolong consumption, Monodora myristica seed, oral administration, hepatoprotective, liver enzymes, antioxidant system

Andrographis paniculata Ethanolic Extract Improved Doxorubicin-induced Cardiac Inflammation, Alterations in Liver Function Parameters and Anemia

Background: Doxorubicin (DOX), an efficacious chemotherapy drug is compromised by cardiotoxicity, myelosuppression, and hepatotoxicity. Due to the limited success of current treatments for DOX toxicity, there is a pressing need to explore alternative medical interventions, particularly from plant sources. This study was conducted to investigate the potential protective effect of ethanolic extract of Andrographis paniculata leaves (EEAP) against DOX-induced cardiac inflammation, liver toxicity, and anemia.Materials and methods: Sprague-Dawley rats were intraperitoneally injected with DOX at a total dose of 16 mg/kgBW. EEAP was administered orally for 4 weeks at doses of 125, 250, and 500 mg/kgBW/day according to the assigned treatment groups. The mRNA expression levels of interleukin-1β (IL-1β) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) in the heart tissue, along with the concentrations of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and calcium level were examined. Additionally, the hematological parameters (including hematocrit, hemoglobin and red blood cells (RBCs)), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and malondialdehyde (MDA) levels in blood were also analyzed.Results: EEAP dose-dependently decreased the mRNA expressions of IL-1β (p&lt;0.05), tended to decrease mRNA expression of NLRP3 and the concentrations of NFκB and calcium in heart tissue compared with the DOX-only group. Additionally, EEAP dose-dependently decreased ALP values (p&lt;0.0001) and tended to improve hematological parameters, as well as AST and MDA levels in serum.Conclusion: This extract may prevent DOX-induced cardiac inflammation, anemia, and hepatotoxicity. However, further studies are needed to confirm these findings, including the efficacy profile of the extract in cancer rats treated with DOX.Keywords: doxorubicin, Andrographis paniculata, inflammation, anemia, hepatotoxicity, herbal medicine

Ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry-characterized extract of Aerides odorata Lour alleviates paracetamol-induced hepatotoxicity in animal model evidenced by biochemical, molecular, and computational studies.

Many kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol-induced liver damage-protecting effect of epiphytic Aerides odorata methanol extract (AODE). The protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand-receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses. AODE significantly (p < 0.05) minimized the dose-dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, and total bilirubin compared to the reference drug silymarin. Malondialdehyde level decreased, and the antioxidant genes catalase (CAT), superoxide dismutase (SOD), β-actin, paraoxonase-1 (PON1), and phosphofructokinase-1 (PFK-1) were upregulated in AODE-treated paracetamol-intoxicated rats. A total of 376 compounds comprising phenols and flavonoids were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-qTOF-MS). The online toxicity assessment using SwissADME and admetSAR exhibited drug-like, nontoxic, and potential pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (-11.42) with the liver protein human pituitary adenylate cyclase-1 (Protein Data Bank ID: 3N94). Furthermore, network pharmacology analysis identified the top 10 hub genes, namely AKT1 (protein kinase B), CTNNB1 (catenin beta-1), SRC (proto-oncogene c-Src), TNF (tumor necrosis factor), EGFR (epidermal growth factor receptor), HSP90AA1 (heat shock protein 90α), MAPK3 (mitogen-activated protein kinase 3), STAT3 (signal transducer and activator of transcription 3), CASP3 (caspase protein), and ESR1 (estrogen receptor 1), which are responsible for hepatoprotective activity. The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound-based animal study.

Association of HLA-G 3'UTR polymorphisms with hepatitis B virus infection in Tunisian population.

Hepatitis B virus (HBV) infection is a major public health burden. The mechanisms of immune evasion during chronic HBV (CHB) infection are poorly understood. Human leukocyte antigen (HLA)-G, an immune checkpoint molecule, plays a crucial role in the tolerance mechanisms of various infectious diseases. The 3' untranslated region (3'UTR), including the HLA-G + 3142 C > G polymorphism (rs1063320) and the 14-pb Ins/Del (rs66554220) has been strongly suggested to influence HLA-G expression. This study conducted a case-control analysis to evaluate the potential correlation between the HLA-G + 3142 C > G polymorphism and HBV infection outcome in a Tunisian cohort. The HLA-G + 3142 C > G polymorphism was analysed by PCR-RFLP in 242 patients with chronic HBV infection (116 males and 126 females), 241 healthy controls (116 males and 125 females), and 100 spontaneously resolved subjects (52 males and 48 females). Patients with chronic HBV infection showed a higher frequency of the + 3142G allele compared to healthy controls and spontaneously resolved subjects (p = 0.001 and p = 0.002, respectively). An association between the + 3142G allele and high HBV DNA levels was observed when HBV patients were stratified based on their HBV DNA levels (p = 0.016). Furthermore, the dominant model (GG + GC vs CC) was associated with liver function parameters, including AST, ALT, and high HBV DNA levels (p = 0.04, p < 0.001 and p = 0.002, respectively). However, there was no significant association found between this polymorphism and the fibrosis stage (p = 0.32). The haplotype analysis, using a subset of previously published data on the HLA-G 14-pb Ins/Del polymorphism, revealed an association between the Ins/G haplotype and chronic HBV infection (H1: InsG, p < 0.001). Our findings suggest that the + 3142G allele is a risk factor for the persistence and progression of HBV infection, while the + 3142C allele serves as a protective allele associated with the spontaneous resolution of the infection. Additionally, the HLA-G 3'UTR haplotype Ins/G is associated with chronic HBV infection in the Tunisian population.

Directly Acting Anti-Viral Drugs and Its Metabolic Side Effects in Patients with Chronic HCV

Abstract Background Hepatitis C virus (HCV) is a major cause of chronic liver disease, with an estimated 170 million people infected worldwide. Treatment of hepatitis C virus has traditionally been difficult because of low rates of treatment success and high rates of treatment discontinuation due to side effects. Aim of the Work The aim of this work is to study side effects of directly acting anti HCV drug (DAA) and its progression in metabolism of lipid profile, blood sugar level, and renal function. Patients and Methods This case study had been carried out on 200 subjects presented to Department of Internal Medicine at Kobbri ELkobba hospital inpatient and outpatient clinics between March 2016 and September 2016. Results sustained virological response (12 weeks) after end of the treatment in more than 90% of patients, Liver function parameters including albumin, bilirubin, and prothrombin time and liver enzymes Ast, Alt improved in the majority of patients during and after the end of therapy,but there is significant increase in urea level, serum creatinin and HbA1C. There is significant decrease in LDL and mild increase in TG level. Conclusion Once-daily oral daclatasvir plus sofosbuvir with or without Ribavirin was associated with high rates of sustained virologic response among patients infected with HCV, including chronic cirrhotic patients and relapsers, successful treatment associated with Improvement of liver function parameters in the majority of patients, Increase in urea level, serum creatinin and HbA1C. There is significant decrease in LDL and mild increase in TG level.

Toxicological Effects of Colloidal Silver Nanoparticles on Rat Health: Assessing Physiological, Hematological, Biochemical, and Behavioral Parameters

Introduction: Nanotechnology, a rapidly evolving field, has introduced silver nanoparticles (AgNPs) as promising materials with diverse applications. Their unique properties have revolutionized industries, raising concerns about potential health implications. This study aims to comprehensively evaluate the toxicological effects of AgNPs on rat health through a multidimensional approach, encompassing physiological, hematological, biochemical, and behavioral assessments. Methodology: Colloidal AgNPs with a minimum purity of 99.98% were synthesized using an inductive coupled plasma (ICP) method. Sixty male specific-pathogen-free (SPF) Wistar rats were exposed to low (10 μg/kg/day) and high (100 μg/kg/day) doses of AgNPs, alongside a control group. Throughout the exposure period, comprehensive assessments, including body weight changes, food intake, water consumption, hematological and biochemical parameters, and behavioral evaluations, were systematically conducted. The statistical analysis employed a combination of one-way ANOVA and Kruskal-Wallis tests for robust data interpretation. Results: Rats exposed to low (10 μg/kg/day) and high (100 μg/kg/day) doses of AgNPs displayed no significant changes in food intake, water consumption, or blood parameters compared to the control group. However, a notable reduction in body weight was observed in the high-dose group, suggesting a potential dose-dependent impact. Biochemical analyses indicated no significant differences in liver and kidney function parameters for the low-dose group, but the high-dose group exhibited potential elevation in liver enzymes, necessitating further scrutiny. Behavioral assessments revealed no significant alterations in open-field behavior or cognitive function, indicating minimal impact on exploratory and cognitive abilities within the tested doses. Conclusion: AgNPs demonstrated minimal impact on certain parameters, the high-dose group exhibited notable body weight reduction and potential liver enzyme alterations, warranting further investigation. Behavioral assessments indicated no significant cognitive effects. These findings emphasize the importance of continued research for informed regulatory decisions and the safe utilization of AgNPs in consumer products.