Biochemical Markers Of Liver Function Research Articles

Smoke Signals: Unraveling the Link between Cigarette Smoking and Serum Liver Markers

Introduction: Cigarette smoking is a major cause of global mortality and morbidity. It exposes the body to many harmful substances, such as cytotoxic, carcinogenic and free radicals, that can damage various organs. This study aims to investigate the effects of different levels of tobacco exposure on liver tissue, by measuring some serum biochemical markers of liver function.
 Materials and Methods: The project conducted at T.N.M.C Mumbai from January to December 2021 involved 60 male participants (18–35 years old), divided into smokers (30) and non-smokers (30). Smokers had varying smoking durations (1-5 years). Excluded participants with diseases affecting liver enzymes. Groups were age-matched for analysis. Smokers defined as those smoking >20 cigarettes daily for >1 month. Collected 5.0 ml venous blood, processed in heparinized tubes, and centrifuged for plasma separation. Enzymes SGOT, SGPT, ALP, Total Bilirubin, Direct Bilirubin were measured, and statistical analysis revealed significant differences.
 Results: In the study, age comparison between smokers and non-smokers showed no significant difference (p = 0.71). However, smokers exhibited significantly higher mean serum concentrations of SGOT and SGPT compared to non-smokers (p = 0.002 and p < 0.0001, respectively). Smokers also had elevated levels of ALP and total bilirubin with mean differences of 16.3 IU/L and 0.392 mg/dl, supported by 95% confidence intervals (6.72, 26.18) and (0.28, 0.504) and p values of 0.003 and 0.0004, respectively. No significant difference was observed in direct bilirubin levels (mean difference: 0.084 mg/dl, 95% CI: 0.065, 0.103, p = 0.191)
 Conclusion: In summary, the study suggests a correlation between smoking and elevated serum levels of liver enzymes and damage markers, indicating a potential adverse impact on liver function and increased susceptibility to liver diseases.

Alterations in Biochemical Markers of Liver and Kidney Function and Oxidative Stress Indices on Sub-acute Exposure of Meloxicam in Albino Rats

Background: The study was performed to study the alterations in biochemical markers of liver and kidney function and oxidative stress indices on sub-acute exposure of meloxicam in albino rats. Methods: The study was performed in three groups of rats, consisting six rats in each group. The rats of group I were served as control. However, rats of group II, III were treated with meloxicam @ 0.2 mg/kg b.wt. meloxicam @ 0.6 mg/kg b.wt. respectively. Result: Meloxicam administration induced oxidative stress in rats as indicated by significant decrease in concentration of catalase, superoxide dismutase and reduced glutathione in blood as compared to control. However, lipid peroxidation was significantly enhanced as indicated by increased level of MDA in blood as compared to control. Meloxicam altered the functions of liver and kidney as indicated by the alteration in the biochemical markers of liver and kidney function. Meloxicam significantly enhanced the concentration of biochemical markers of liver function viz. ALT, AST, GGT, ALP, albumin and bilirubin as compared to control. The concentration of biochemical markers of kidney function viz. BUN and creatinine was significantly enhanced after meloxicam administration as compared to control.

α-Lipoic Acid Protects against Cyclosporine A-Induced Hepatic Toxicity in Rats: Effect on Oxidative Stress, Inflammation, and Apoptosis.

The clinical application of cyclosporine A (CsA) as an immunosuppressive agent is limited by its organ toxicity. We aimed to evaluate the effectiveness of α-lipoic acid against CsA-induced hepatotoxicity and to delineate the underlying molecular mechanisms. Male Wistar rats (n = 24, 8 per each group) received the vehicle, CsA (25 mg/kg) and/or ALA (100 mg/kg, p.o.) for 3 weeks. Biochemical markers of liver function (serum ALT, AST, ALP < GGT), oxidative stress (MDA, TAC, SOD, GSH, Nrf2/HO-1), inflammation (NF-κB, CD68, iNOS, NO, COX-2), and apoptosis (caspase-3) were assessed in serum and tissue. Liver histological analysis using H&E and Sirius red was performed. The development of liver injury in CsA-treated animals was indicated by elevated levels of liver enzymes, oxidants/antioxidants imbalance, inflammatory cells infiltration, up-regulated expression of inflammatory mediators, and apoptosis. These changes were associated with altered architecture of hepatic cells and fibrous connective tissue. ALA co-administration protected against CsA-induced liver damage and ameliorated biochemical changes and cellular injury. In conclusion, ALA demonstrated hepatoprotective potential against CsA-induced liver injury through combating oxidative stress, inflammation, and apoptosis, highlighting ALA as a valuable adjunct to CsA therapy.

Debating capabilities of biochemical markers of liver function in patients with alcoholic liver cirrhosis

Introduction. The diagnosis of alcohol-related liver disease is limited by the lack of a tool to reliably identify whether the present deterioration in the patient’s condition is due to alcohol consumption or other causes.Purpose. to conduct a comparative assessment of the clinical and diagnostic significance of liver function biochemical indicators (AST, ALT, GGT, ALP) and their calculated derivatives (AST/ALT, GGT/ALP, GGT/GGTn, ALP/ALPn) as markers of alcohol consumption in patients with alcoholic liver cirrhosis.Material and methods. The observational study included 112 men over 18 years of age with alcohol-related liver cirrhosis. The patients were assessed the severity of liver cirrhosis according to the Child-Pugh scale, performed general and biochemical blood tests, coagulation test, assessment of the fact of alcohol consumption by the level of phosphatidylethanol. An analysis was made of the relationship between alcohol consumption and changes in laboratory parameters of liver function, with the determination of their sensitivity and specificity.Results. Patients with Child-Pugh B cirrhosis who consumed alcohol on phosphatidylethanol had higher levels of plasma albumin, GGT, and lower values of creatinine, direct and total bilirubin, urea, and aPTT compared with patients who did not drink alcohol (p &lt; 0.05). Alcohol-drinking patients with class C cirrhosis have higher ALT levels compared with abstinent patients with the same severity of cirrhosis (p &lt; 0.05). The relationship between the fact of alcohol consumption, determined by the level of phosphatidylethanol, and the ratio of GGT of patients to the normal GGT value, as well as between the ratio of GGT to alkaline phosphatase and the degree of increase in GGT, turned out to be statistically significant. To assess the fact of alcohol consumption, the level of serum GGT &gt; 65 IU/ l (75.5%) has the highest sensitivity, the highest specificity is the ratio of the patient’s GGT to the normal value of GGT &gt; 2 (82.9%).Conclusion. Compared with the known 100% sensitivity and &gt; 92% specificity of Peth as a alcohol biomarker, among the biochemical indicators of liver function and their calculated derivatives, GGT &gt; 65 IU/l have the greatest sensitivity or specificity (respectively, 75.5% and 65%) and GGTnorm. &gt; 2 (37.7% and 82.9%, respectively), which makes it possible to use the totality of these parameters as an indicator of the continued impact on the patient of the main etiological factor of alcohol-related liver cirrhosis in the routine practice of most medical organizations of the Russian Federation.

Repeated partial splenic artery embolization for hypersplenism improves platelet count.

Splenic embolization is a minimally invasive alternative to splenectomy for the treatment of hypersplenism. This was a retrospective study of 101 patients with hypersplenism caused by cirrhosis who were treated with splenic embolization and for whom 6 months of follow-up data were available. Of these patients, 65 underwent partial splenic artery embolization (PSE), including 23 who underwent repeated PSE (RPSE). The incidence of abdominal pain was significantly higher in the PSE group than in the total splenic artery embolization (TSE) group (P < 0.001), and its duration was also longer in the PSE group (P = 0.003). Biochemical markers of liver function were compared before and after the operation; aminotransferase indices decreased (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), total bilirubin increased slightly, and albumin and prealbumin decreased after the operation (all P < 0.001). Platelet (PLT) counts began to increase at 1 week postoperatively, peaked at 1 month postoperatively, and then decreased gradually. There was no significant intergroup (PSE and TSE) difference at any time point (1 day, 1 week, 1 month, and 6 months postoperatively, P > 0.05). There was a significant intergroup (PSE and RPSE) difference in the mean postoperative change in PLT count (P = 0.45). Splenic embolization can improve the inflammatory indicators of liver function. Performing PSE twice or more improves the PLT counts.

Specific fluorescence release based on synergistic activation of enzymes and position-dependent of electrophilic groups to diagnose intrahepatic cholestasis of pregnancy

The early diagnosis and effective treatment of disease have presented new challenges to today's researchers. Recently, an important direction of the development of the fluorescent probes field is to provide convenient detection tools for clinical diagnosis. Intrahepatic cholestasis of pregnancy (ICP), a pregnancy-specific liver disease associated with poor maternal and fetal outcome, lack biochemical diagnosis indicator with relatively high specificity. Glutathione S-transferases may be a potential candidate for ICP diagnosis owing to their high concentrations in the liver, however, fluorescent detection tool for GSTs with high selectivity is scarce, owing to the interference of high non-enzymatic reaction with GSH. In this work, a probe (MB5) through fine structure regulation for specific fluorescence response GSTs was obtained with synergistic activation of enzymes and position-dependent of electrophilic groups. Furthermore, overexpressed GSTs were visualized directly in cholestatic mice models through in vivo imaging, isolated organ imaging, and tissue slice analysis. More importantly, the serum samples of the ICP patients hold significantly high levels of GSTs concentrations, compared with healthy pregnant women. Therefore, a novel diagnostic tool and excellent detection method for ICP were provided, which will promote to the establishment of new biochemical markers of liver function in pregnancy.

Pharmacokinetics of isoniazid in Wistar rats exposed to ethanol

Tuberculosis treatment consists of a drug combination, where isoniazid is the core drug and alcoholism is a factor highly related to poor patient compliance with the therapy. CYP2E1 is an enzyme involved both in the metabolism of ethanol and in the formation of hepatotoxic compounds during the metabolism of isoniazid. The shared metabolism pathway accounts for the possibility of pharmacokinetic interaction in cases of concomitant alcohol use during tuberculosis treatment. The aim of this study was to evaluate the effect of repeated exposure of Wistar rats (males, 250 g, n=6) to ethanol on the pharmacokinetics of a single dose of isoniazid in combination with pyrazinamide and rifampicin (100 mg/kg, 350 mg/kg and 100 mg/kg, respectively). An animal group received the combination of drugs and ethanol and was compared to a control group, which received the combination of drugs without exposure to ethanol. The plasma concentrations of isoniazid were determined by a UHPLC/UV bioanalytical method that was previously validated. Biochemical markers of liver function were measured to assess potential damage. A lower elimination half-life of isoniazid was observed in the ethanol group than in the control group (t1/2 0.91 h versus 1.34 h). There was no evidence of hepatotoxicity through the biomarker enzymes evaluated. The results allow us to infer that although there are no biochemical changes related to liver damage, there is a slight influence of ethanol exposure on the pharmacokinetic profile of isoniazid. This change may have a relevant impact on the efficacy of isoniazid in the outcome of tuberculosis treatment.

Alterations in Biochemical Markers of Liver and Kidney Function and Oxidative Stress Indices on Sub-acute Exposure of Enrofloxacin in Albino Rats

Background: The present study was performed to evaluate Alterations in biochemical markers of liver and kidney function and oxidative stress indices on sub-acute exposure of enrofloxacin in albino rats. Methods: Albino rat weighing 200-300 gm were treated with enrofloxacin orally with the help of gavage needle and devided into three groups each group consist six rats. The rats of group I were served as control. However, rats of group II and III were treated with enrofloxacin @ 5 mg/kg b.wt., enrofloxacin @ 10 mg/kg b.wt. respectively. All the groups received medication orally, once daily for 28 days and blood samples were collected on the 28 day of experiment by the help of capillary tube and processed by laboratory methods. Result: Enrofloxacin altered the functions of liver and kidney as indicated by the alteration in the biochemical markers of liver and kidney function. Enrofloxacin significantly enhanced the concentration of biochemical markers of liver function viz. ALT, AST, GGT, ALP, albumin and bilirubin as compared to control. The concentration of biochemical markers of kidney function viz. BUN and creatinine was significantly enhanced after enrofloxacin administration as compared to control. Enrofloxacin administration induced oxidative stress in rats as indicated by significant decrease in concentration of catalase, superoxide dismutase and reduced glutathione in blood as compared to control. However, lipid peroxidation was significantly enhanced as indicated by increased level of MDA in blood as compared to controlConclusion: Thus, enrofloxacin have ability to altered the biochemical markers of liver and kidney and also have potency to induced oxidative stress in albino rats after the sub-acute exposure for 28 days.

Ameliorative effect of Ruzu herbal bitters on high-fat diet induced non-alcoholic fatty liver disease in Wistar rats

Context: One of the world’s most widespread and frequent liver diseases is the non-alcoholic fatty liver disease (NAFLD). Aims: To evaluate the preventives activities of Ruzu herbal bitters (RHB), which is an anti-obesity therapeutic concoction used widely in Nigeria on high–fat diet (HFD) induced NAFLD in albino Wistar rats. Methods: A total number of twenty-five rats were isolated and divided equally into five groups. Group 1, the normal control group was placed on normal rat diet and normal saline (1 mL/kg body weight daily) for twelve weeks. The remaining four groups 2-5 were placed on HFD for twelve weeks; adding to the following treatment schedules by oral gavage: group 2 received pioglitazone 4 mg/kg daily, group 3 received RHB 0.6 mL/kg daily, group 4 received normal saline 1 mL/kg daily and group 5 received fenofibrate 10 mg/kg daily (s.c). The animals were sacrificed and biochemical markers of liver function, lipid profile, glycemic index, and histopathological assessment of the liver of the rats were determined. Results: Rat treated with RHB and other treated groups significantly (p&lt;0.05) reduced the liver index, fasting blood glucose, and activities and concentrations of liver function enzymes and molecules when compared to untreated NAFLD group. Scoring of hepatic steatosis also showed the ameliorative role of the treatment on NAFLD. Conclusions: This study reveals that RHB and other treatment options assessed could prevent HFD–induced NAFLD and could be explored as another therapeutic approach to fenofibrate and pioglitazone in NAFLD management.

Liver dysfunction in COVID-19: a useful prognostic marker of severe disease?

BackgroundCOVID-19 is a global pandemic caused by the novel coronavirus SARS-CoV-2. Risk factors and prognostic markers of severe disease remain to be fully determined, although some studies have suggested a...

Metalloproteinase expression after desflurane preconditioning in hepatectomies: A randomized clinical trial.

BACKGROUNDHepatectomy with inflow occlusion results in ischemia-reperfusion injury; however, pharmacological preconditioning can prevent such injury and optimize the postoperative recovery of hepatectomized patients. The normal inflammatory response after a hepatectomy involves increased expression of metalloproteinases, which may signal pathologic hepatic tissue reformation. AIMTo investigate the effect of desflurane preconditioning on these inflammatory indices in patients with inflow occlusion undergoing hepatectomy.METHODSThis is a single-center, prospective, randomized controlled trial conducted at the 4th Department of Surgery of the Medical School of Aristotle University of Thessaloniki, between August 2016 and December 2017. Forty-six patients were randomized to either the desflurane treatment group for pharmacological preconditioning (by replacement of propofol with desflurane, administered 30 min before induction of ischemia) or the control group for standard intravenous propofol. The primary endpoint of expression levels of matrix metalloproteinases and their inhibitors was determined preoperatively and at 30 min posthepatic reperfusion. The secondary endpoints of neutrophil infiltration, coagulation profile, activity of antithrombin III (AT III), protein C (PC), protein S and biochemical markers of liver function were determined for 5 d postoperatively and compared between the groups.RESULTSThe desflurane treatment group showed significantly increased levels of tissue inhibitor of metalloproteinases 1 and 2, significantly decreased levels of matrix metalloproteinases 2 and 9, decreased neutrophil infiltration, and less profound changes in the coagulation profile. During the 5-d postoperative period, all patients showed significantly decreased activity of AT III, PC and protein S (vs baseline values, P < 0.05). The activity of AT III and PC differed significantly between the two groups from postoperative day 1 to postoperative day 5 (P < 0.05), showing a moderate drop in activity of AT III and PC in the desflurane treatment group and a dramatic drop in the control group. Compared to the control group, the desflurane treatment group also had significantly lower international normalized ratio values on all postoperative days (P < 0.005) and lower serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase values on postoperative days 2 and 3 (P < 0.05). Total length of stay was significantly less in the desflurane group (P = 0.009).CONCLUSIONDesflurane preconditioning can lessen the inflammatory response related to ischemia-reperfusion injury and may shorten length of hospitalization.

Chinese herbal medicine mixture 919 syrup alleviates nonalcoholic fatty liver disease in rats by inhibiting the NF-κB pathway

BackgroundIn many countries, nonalcoholic fatty liver disease (NAFLD) has risen to be the leading cause of liver disease, seriously threatening public health, while effective medical treatments are currently limited. 919 syrup (919 T J) is a Chinese herbal medicine, and both clinical and experimental studies have revealed that it can improve liver function. ObjectiveTo study whether 919 T J shows a protective effect in a NAFLD rat model and explore its underlying mechanism, with a focus on the NF-κB pathway. MethodsRats were randomly divided into three groups, including a control group, NAFLD group, and 919 T J group (n = 10 each). The control group received a standard diet, and the other two groups were fed a high-fat diet to establish the NAFLD model. From week 10, rats in the 919 T J group were intragastrically administered 919 T J for 4 weeks, and the NAFLD group was administered the same amount of saline. All rats were anesthetized at the beginning of week 14 to collect blood and liver specimens. Serum lipid levels, serum biochemical markers of liver function, and the gene expression levels of IL-1β, TNF-α, CXCL6, CXCR1, SREBP-1c, PPARγ, and NF-κB in the liver were measured. Oil Red O and hematoxylin and eosin staining of the liver was performed to observe pathological changes in the liver. ResultsSignificant abnormalities in serum lipid levels and serum biochemical markers of liver function were found in the NAFLD group relative to those in the control group. In addition, serious abnormalities were noted in the expression levels of liver inflammatory factors and lipid metabolism-related genes. Treatment of NAFLD rats with 919 T J reduced body weight and food intake and ameliorated the abnormal blood lipid levels and liver function markers. By regulating the NF-κB pathway, 919 T J downregulated the NF-κB-related proinflammatory signals, ameliorating the expression of inflammatory (IL-1β, TNF-α, CXCL6, and CXCR1) and lipid metabolism-related (SREBP-1c) factors in the liver and improving the NAFLD-induced pathological changes in the liver. Conclusion919 T J reduces the liver injury, steatosis, and inflammation caused by NAFLD, thus reversing the disease process.

Ultrasound-targeted microbubble destruction optimized HGF-overexpressing bone marrow stem cells to repair fibrotic liver in rats

Background/aimsBone marrow mesenchymal stem cells (BMSCs) have shown their therapeutic potential in cytotherapy for liver fibrosis. However, the insufficient homing of BMSCs and undefined proliferation of BMSCs represent a significant challenge and largely limit the effective implementation. The aims of the present study were to determine whether stable expression of hepatic growth factor (HGF) in BMSCs coupled with ultrasound-targeted microbubble destruction (UTMD) technique could effectively and definitely alleviating carbon tetrachloride (CCl4)-induced liver fibrosis in rats.Materials and methodsA rat model of liver fibrosis was acquired by injection of carbon tetrachloride (CCl4). The experimental rats were randomly assigned to the four groups: normal, CCl4, BMSCs-HGF/US, and BMSCs-HGF/UTMD groups. The BMSCs, transfected by recombinant adeno-associated virus vector encoding human genome sequence of HGF (BMSCs-HGF), were transplanted in rat via the tail vein. The homing efficiency of BMSCs was observed by immunofluorescence staining. The liver function and its morphological changes were analyzed by biochemical tests and liver histology. The expression of liver fibrosis markers including α-smooth muscle actin (α-SMA), collagen I, and vimentin were examined by immunohistochemistry and quantitative real-time polymerase chain reaction.ResultsThe homing efficiency of BMSCs in the fibrotic liver was significantly greater with the application of UTMD. The biochemical markers of liver function and histopathological results showed significantly better improvement in BMSCs-HGF/UTMD group than the other groups, and the serum levels of biochemical markers returned to normal ranges in 12 weeks in this group. Furthermore, the expression levels of liver fibrosis markers (α-SMA, collagen I, and Vimentin) were all significantly lower in BMSCs-HGF/UTMD group in comparison with other groups.ConclusionsOur findings have demonstrated that stable expression of HGF in BMSCs and application of the UTMD technique facilitate the homing of BMSCs, and more importantly, which could further improve their alleviation of liver fibrosis. Therefore, these findings have an important clinical implication that AAV-BMSCs-HGF and UTMD hold promise as a novel therapeutic approach for liver fibrosis.

Chronic Cholangiopathy Associated with Primary Immune Deficiencies Can Be Resolved by Effective Hematopoietic Stem Cell Transplantation

To investigate effects and outcome of hematopoietic stem cell transplantation (HSCT) on sclerosing cholangitis, in pediatric patients with different primary immunodeficiencies (PIDs). From databases in 2 tertiary centers for immunodeficiencies and liver disease, we have identified children with PIDs and sclerosing cholangitis, who have paired clinical, radiologic, and histologic information before and after HSCT and studied their clinical progress and outcome. Seven of 13 children (53.8%) died at a median interval of 4months (range, 3 months-5 years) after HSCT. However, 6 surviving children (46.2%) with different PIDs and less severe cholangiopathies showed an improvement in markers of liver injury within months of successful unrelated reduced intensity conditioning HSCT. The repeated native liver biopsy, performed in 4 patients at a median of 96 (range, 4-144) months post-HSCT, showed a considerable improvement. Biochemical markers of liver function in the survivors completely normalized after a median of 13months (range, 2-48). All patients continue to have a mildly dilated extrahepatic biliary system on ultrasonography with no intrahepatic ductal changes on magnetic resonance cholangiography after a follow-up of median 18years (range, 2-20). Effective HSCT has the potential to improve biochemical and histologic features of cholangiopathy in children with PIDs, presumably by clearance of chronic infection following establishment of immune competence. However, careful patient selection is critical as advanced liver injury is often associated with serious complications and mortality.

Protective role of c-Jun N-terminal kinase-2 (JNK2) in ibuprofen-induced acute liver injury.

Ibuprofen is a worldwide used non-steroidal anti-inflammatory drug which may cause acute liver injury (ALI) requiring liver transplantation. We aimed to unveil the molecular pathways involved in triggering ibuprofen-induced ALI, which, at present, remain elusive. First, we investigated activation of essential pathways in human liver sections of ibuprofen-induced ALI. Next, we assessed the cytotoxicity of ibuprofen in vitro and developed a novel murine model of ibuprofen intoxication. To assess the role of JNK, we used animals carrying constitutive deletion of c-Jun N-terminal kinase 1 (Jnk1-/- ) or Jnk2 (Jnk2-/- ) expression and included investigations using animals with hepatocyte-specific Jnk deletion either genetically (Jnk1Δhepa ) or by siRNA (siJnk2Δhepa ). We found in human and murine samples of ibuprofen-induced acute liver failure that JNK phosphorylation was increased in the cytoplasm of hepatocytes and other non-liver parenchymal cells (non-LPCs) compared with healthy tissue. In mice, ibuprofen intoxication resulted in a significantly stronger degree of liver injury compared with vehicle-treated controls as evidenced by serum transaminases, and hepatic histopathology. Next, we investigated molecular pathways. PKCα, AKT, JNK and RIPK1 were significantly increased 8h after ibuprofen intoxication. Constitutive Jnk1-/- and Jnk2-/- deficient mice exhibited increased liver dysfunction compared to wild-type (WT) animals. Furthermore, siJnk2Δhepa animals showed a dramatic increase in biochemical markers of liver function, which correlated with significantly higher serum liver enzymes and worsened liver histology, and MAPK activation compared to Jnk1Δhepa or WT animals. In our study, cytoplasmic JNK activation in hepatocytes and other non-LPCs is a hallmark of human and murine ibuprofen-induced ALI. Functional in vivo analysis demonstrated a protective role of hepatocyte-specific Jnk2 during ibuprofen ALI. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Irinotecan and Δ⁸-Tetrahydrocannabinol Interactions in Rat Liver: A Preliminary Evaluation Using Biochemical and Genotoxicity Markers.

There is growing interest regarding the use of herbal preparations based on Cannabis sativa for medicinal purposes, despite the poorly understood interactions of their main constituent Δ9-tetrahydrocannabinol (THC) with conventional drugs, especially cytostatics. The objective of this pilot study was to prove whether the concomitant intake of THC impaired liver function in male Wistar rats treated with the anticancer drug irinotecan (IRI), and evaluate the toxic effects associated with this exposure. IRI was administered once intraperitoneally (at 100 mg/kg of the body weight (b.w.)), while THC was administered per os repeatedly for 1, 3, and 7 days (at 7 mg/kg b.w.). Functional liver impairments were studied using biochemical markers of liver function (aspartate aminotransferase—AST, alanine aminotransferase—ALP, alkaline phosphatase—AP, and bilirubin) in rats given a combined treatment, single IRI, single THC, and control groups. Using common oxidative stress biomarkers, along with measurement of primary DNA damage in hepatocytes, the degree of impairments caused at the cellular level was also evaluated. THC caused a time-dependent enhancement of acute toxicity in IRI-treated rats, which was confirmed by body and liver weight reduction. Although single THC affected ALP and AP levels more than single IRI, the levels of liver function markers measured after the administration of a combined treatment mostly did not significantly differ from control. Combined exposure led to increased oxidative stress responses in 3- and 7-day treatments, compared to single IRI. Single IRI caused the highest DNA damage at all timepoints. Continuous 7-day oral exposure to single THC caused an increased mean value of comet tail length compared to its shorter treatments. Concomitant intake of THC slightly affected the levels of IRI genotoxicity at all timepoints, but not in a consistent manner. Further studies are needed to prove our preliminary observations, clarify the underlying mechanisms behind IRI and THC interactions, and unambiguously confirm or reject the assumptions made herein.

Biochemical Markers of Liver Function in Smoking and Non-Smoking Alcohol-Dependent Males

Biochemical Markers of Liver Function in Smoking and Non-Smoking Alcohol-Dependent Males

Vitamin A status and its determinants in patients with cystic fibrosis.

Routine administration of vitamin A, recommended in CF patients, can help to prevent its deficiency. However, high vitamin A supplementation may lead to its excessive level and possible toxicity. Therefore, the aim of the present study was to assess the status of vitamin A and the determinants of its body resources in CF patients. In 196 CF patients aged from 4 months to 47 years, the following parameters were analysed: nutritional status (standardized body weight and height, serum albumin concentration) and clinical expression of disease (lung function - spirometry; biochemical markers of liver function - ALT, AST, GGT; respiratory tract colonization by Pseudomonas aeruginosa; diabetes; cirrhosis, non-cirrhotic liver disease; exocrine pancreatic function - fecal elastase-1 concentration; blood clotting - INR and vitamin A supplementation). Median vitamin A concentration in the study group was 383.0 ng/ml (1st-3rd quartile: 316.5-457.0). Vitamin A deficiency was found in 32 (16.3%) subjects studied. Vitamin A concentrations above the reference range were observed only in 3 (1.5%) CF patients. CF patients with vitamin A deficiency were significantly older and had lower values of FEV1 compared to CF subjects with normal vitamin A status. Moreover, vitamin A deficiency occurred more frequently in CF patients with diabetes, Pseudomonas aeruginosa colo- nization, worse lung function and in those without vitamin A supplementation. However, in multiple linear regression analyses, none of the independent variables was documented to be important for predicting vita- min A status. Vitamin A body resources in CF patients are mostly normal. Moreover, there are no good de- terminants of vitamin A status in these patients. Further studies targeted at exploring potential toxicity and deficiencies of vitamin A in CF patients are needed.

English

Co-infection with HIV and hepatitis B virus (HBV) has become an important factor of co-morbidity and mortality. The aim of this study was to determine the seroprevalence of HIV/HBV co-infection and its effect on the disease progression in people living with HIV/AIDS identified in Yaound&eacute; Central Hospital. Blood samples from 75 HIV positive patients were collected in Yaound&eacute; Central Hospital from November 2015 to February 2016, for the determination of hepatitis B virus surface antigen (HBsAg) using immunoassays. Cluster of differentiation 4 (CD4) T-cells count and biochemical markers of liver function were also collected and analyzed. The socio-demographic data were also collected. The effect sizes were confirmed using G*Power version 3.1.9.2 software. The data were entered and analyzed using the SPSS Version 22.1 software.&nbsp; The statistical tests performed were x2, and Pearson correlation, with significant difference at the threshold p &le; 0.05. Hepatitis B virus surface antigen (HBsAg) was identified in 12 patients out of 75 HIV-positive patients, for a HIV/HBV co-infection prevalence of 16%. The co-infection rate was higher in women 9 (12%) than in men 3 (4%). Among HIV infected patients, a negative and significant correlation was observed between CD4 count and ALT activity, and between the concentration of conjugated bilirubin and the activity of alkaline phosphatase (ALP) p&le; 0.05. The prevalence of HIV/HBV co-infection is higher among HIV positive patients in the Yaound&eacute; Central Hospital. HIV associated with HBV plays a role in the disease progression. Consequently, it is important that a national management programme is in place in the country to monitor the incidence and morbidity rates of these affections. &nbsp; Key words: Co-infection, seroprevalence, hepatitis B virus (HBV), human immunodeficiency virus (HIV), Cluster of differentiation 4 (CD4) T-cells, liver enzymes, disease progression.

Upregulation of miR-223 in the rat liver inhibits proliferation of hepatocytes under simulated microgravity

Long-term spaceflight affects numerous organ systems in the body, including metabolic dysfunction. Recently, ample evidence has demonstrated that the liver is a vulnerable organ during spaceflight. However, the changes in hepatocyte proliferation and cell cycle control under microgravity remain largely unexplored. In the present study, we first confirmed that the serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, biochemical markers of liver function, were altered in rats under tail suspension (TS) conditions to simulate microgravity, as shown in previous reports. Next, we demonstrated that the cell proliferation activity, determined by Ki67, PCNA and PH3, was significantly decreased at the different TS time points (TS for 14, 28 and 42 days) compared with that in the control group. Consistently, the positive cell cycle regulators Ccna2, Ccnd1, Cdk1, Cdk2 and cyclin D3 were also significantly decreased in the TS groups as shown by quantitative real-time PCR and western blotting analysis. Subsequent analysis revealed that the aberrant hepatocyte proliferation inhibition under simulated microgravity was associated with the upregulation of miR-223 in the liver. We further found that miR-223 inhibited the proliferation of Hepa1-6 cells and identified CDK2 and CUL1 as its direct targets. In addition, the decreased expression of CDK2 and CUL1 was negatively correlated with the level of p27 in vitro and in vivo, which may have been responsible for retarding hepatocyte proliferation. Collectively, these data indicate that upregulation of miR-223 was associated with the inhibition of liver cell growth and reveal the role of miR-223 in rat hepatocyte proliferation disorders and the pathophysiological process under simulated microgravity.