Significant Increase In Alanine Aminotransferase Research Articles

8599 Development of an androgen receptor transgenic mouse that displays the complete attributes of Metabolic Syndrome

Abstract Disclosure: C. Alvarado: None. L.K. Beitel: None. M. Paliouras: None. M.A. Trifiro: None. The mouse androgen receptor (AR) shares over 90% homology with the human ortholog, but it lacks the CAG encoded poly-Q tract; instead, it contains a mixed glutamine/histidine tract. To study AR functionality in a more structured fashion, we created a knock-in mouse model that has only the equivalent of human poly-Q tract while maintaining the remaining mouse receptor sequence intact. Our humanized androgen receptor mouse (AR-19Q) displays a phenotype that is best described as Metabolic Syndrome (MetS). The mice gain excess weight, have hypertension, hyperglycemia, pancreatic islet cell abnormalities, and progressive non-alcoholic fatty liver disease (NAFLD). Features of MetS begin at approximately 4 months and progress till 12-14 months. Obesity: AR-19Q mice are significantly heavier, with a 35% gain of weight vs C57BL/6 mice. However, these mice are not hyperphagic at any time and eat identical quantities of chow. To assess obesity status, and found AR-19Q mice to have a significantly higher depositions of total white adipose visceral, lingual and subcutaneous vs age-matched controls. NAFLD: The progression of NAFLD is observed in AR-19Q mice. AR-19Q Histological analysis and immunohistochemistry reveal microvesicular steatosis, superseded by macrovesicular steatosis with hepatocyte balloon degeneration, scattered lobular inflammation (macrophages and lymphocytes) (6-9 months) and further superseded by perisinusoidal fibrosis (12 months). Biochemical blood analysis confirms. that there is a significant increase in alanine aminotransferase (ALT) levels, indicative of liver damage. With time classical NASH hepatitis and subsequent NASH fibrosis ensues; with several mice developing hepatocellular carcinoma (overall 20% of mice). Gene expression profiling AR-19Q mice for fatty liver genes, we observe an upregulation of inflammation genes Il-6, Il-10 and Tnf. In addition, increased Lpl (lipoprotein lipase) is indicative of increased blood triglyceride levels. On the other hand, down-regulation of G6pc (glucose-6-phosphatase) could be linked to glycogen storage disease. Down-regulation of Slc2a2 and Slc2a4, that encode GLUT2 and GLUT4, should have an influence on glucose levels, glucose homeostasis and insulin sensitivity, as insulin promotes glucose uptake through GLUT4. Type 2 Diabetes: Glucose intolerance is observed by 3-4 months followed by fasting hyperglycemia. Pancreases show advanced islet hyperplasia, concurrent with insulin resistance and type 2 diabetes. Pancreases of middle-age AR-19Q mice present with a significant islet hyperplasia, suggesting peripheral insulin resistance. We propose the use of the AR-19Q mice as a model to study the metabolic dysfunction/ deficiency leading to the MetS. The model will allow us to a better understanding into the mechanisms responsible for T2D and NAFLD-related disorders. Presentation: 6/2/2024

9285 Development of an androgen receptor transgenic mouse that displays the complete attributes of Metabolic Syndrome

Abstract Disclosure: C. Alvarado: None. L.K. Beitel: None. M. Paliouras: None. M.A. Trifiro: None. The mouse androgen receptor (AR) shares over 90% homology with the human ortholog, but it lacks the CAG encoded poly-Q tract; instead, it contains a mixed glutamine/histidine tract. To study AR functionality in a more structured fashion, we created a knock-in mouse model that has only the equivalent of human poly-Q tract while maintaining the remaining mouse receptor sequence intact. Our humanized androgen receptor mouse (AR-19Q) displays a phenotype that is best described as Metabolic Syndrome (MetS). The mice gain excess weight, have hypertension, hyperglycemia, pancreatic islet cell abnormalities, and progressive non-alcoholic fatty liver disease (NAFLD). Features of MetS begin at approximately 4 months and progress till 12-14 months. Obesity: AR-19Q mice are significantly heavier, with a 35% gain of weight vs C57BL/6 mice. However, these mice are not hyperphagic at any time and eat identical quantities of chow. To assess obesity status, and found AR-19Q mice to have a significantly higher depositions of total white adipose visceral, lingual and subcutaneous vs age-matched controls. NAFLD: The progression of NAFLD is observed in AR-19Q mice. AR-19Q Histological analysis and immunohistochemistry reveal microvesicular steatosis, superseded by macrovesicular steatosis with hepatocyte balloon degeneration, scattered lobular inflammation (macrophages and lymphocytes) (6-9 months) and further superseded by perisinusoidal fibrosis (12 months). Biochemical blood analysis confirms. that there is a significant increase in alanine aminotransferase (ALT) levels, indicative of liver damage. With time classical NASH hepatitis and subsequent NASH fibrosis ensues; with several mice developing hepatocellular carcinoma (overall 20% of mice). Gene expression profiling AR-19Q mice for fatty liver genes, we observe an upregulation of inflammation genes Il-6, Il-10 and Tnf. In addition, increased Lpl (lipoprotein lipase) is indicative of increased blood triglyceride levels. On the other hand, down-regulation of G6pc (glucose-6-phosphatase) could be linked to glycogen storage disease. Down-regulation of Slc2a2 and Slc2a4, that encode GLUT2 and GLUT4, should have an influence on glucose levels, glucose homeostasis and insulin sensitivity, as insulin promotes glucose uptake through GLUT4. Type 2 Diabetes: Glucose intolerance is observed by 3-4 months followed by fasting hyperglycemia. Pancreases show advanced islet hyperplasia, concurrent with insulin resistance and type 2 diabetes. Pancreases of middle-age AR-19Q mice present with a significant islet hyperplasia, suggesting peripheral insulin resistance. We propose the use of the AR-19Q mice as a model to study the metabolic dysfunction/ deficiency leading to the MetS. The model will allow us to a better understanding into the mechanisms responsible for T2D and NAFLD-related disorders. Presentation: 6/2/2024

Biochemical and histological changes in two nonalcoholic fatty liver disease models of different severity

Background. One of the priority areas of modern medicine, which unites the interests of various specialists (therapists, cardiologists, gastroenterologists, endocrinologists), is the study of the pathogenesis and clinical manifestations of nonalcoholic fatty liver disease (NAFLD), which is widespread and of unconditional social significance. The search for adequate experimental models of NAFLD that reflect the severity of liver damage is of paramount importance for studying its etiology and pathogenesis.The aim of the study. To compare biochemical and histological changes in experimental models of NAFLD of varying severity.Materials and methods. Two NAFLD model versions were used: a light one – nonalcoholic steatosis (NAS) and a severe variant – non-alcoholic steatohepatitis (NASH). The following biochemical parameters were measured: enzyme activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (AP), plasma glucose concentration, total protein (TP), total bilirubin (TBil) and its conjugate fraction (CB), plasma concentrations of homocysteine (HC), total cholesterol (TC), triacylglycerides (TG), catalase (Cat), superoxide dismutase (SOD) and malondialdehyde (MDA).Results. When used in a model of steatohepatitis, liver function was impaired to a significantly greater extent than in the model of steatosis; this difference was manifested in a statistically significant increase in ALT, AST, AP, TC, Tbil, MDA (p < 0.001) and a decrease in Cat, SOD (p < 0.05). This is confirmed by the development of more pronounced symptoms of disorders of pigment and lipid metabolism, cytolytic and cholestatic syndromes, significant activation of lipid peroxidation and depression of the antioxidant system when modeling non-alcoholic steatohepatitis. Various degrees of severity of morphological changes in the experimental groups were revealed.Conclusion. The study showed the priority of determining biochemical markers, including the levels of ALT, AST, OBIL, TG, MDA and SOD to optimize laboratory methods for diagnosing the severity of liver dystrophy.The practical originality of the results lies in the optimization of the methodology for laboratory diagnosis of the severity of the pathological process in NAFLD.

Mice Hepatic Organoids for Modeling Nonalcoholic Fatty Liver Disease and Drug Response.

Nonalcoholic fatty liver disease (NAFLD) is a serious disease. There are no specific drugs for it, in part because of the lack of effective models to aid drug development. However, it has been shown that three-dimensional organoid culture systems can reproduce the organ structure and maintain the gene expression profile of the original tissue. Therefore, we aimed to construct NAFLD models from liver organoids for pharmacological and mechanism studies. We successfully observed morphological changes in normal liver tissue in mouse liver organoids with positive albumin (ALB) expression and potential for differentiation toward hepatocyte-like cells. The mRNA expression of the hepatocyte markers ALB and hepatocyte nuclear factor 4 alpha increased after liver organoid differentiation. We observed free fatty acid (FFA)-induced lipid accumulation in organoids with significant increases in alanine aminotransferase, aspartate aminotransferase, total bilirubin, and triglyceride levels. Moreover, FFA-induced inflammatory cytokines (interleukin-6, tumor necrosis factor-α, and nitric oxide) and fibrosis indicators (collagen type I α1 and laminin α1) were also increased. In addition, RNA sequencing results showed that the expression of key genes [nucleotide oligomerization domain-like receptor (NLR) family apoptosis inhibitory protein, interferon regulatory factor (IRF) 3, and IRF7] involved in NAFLD metabolic abnormalities and insulin resistance in the NLR signaling pathway was altered after FFA induction of the liver organoids. Finally, we found that JC2-11 and lanifibranor limited the FFA-induced increase in oil-red lipid droplets, liver damage, inflammation, and liver fibrosis. In conclusion, tissue structure, gene expression, and the response of mouse liver organoids to drugs can partially mimic invivo liver tissue. Liver organoids can successfully construct NAFLD models for drug discovery research.

The effect of nitric oxide supplied to the oxygenator of the cardiopulmonary bypass on the functions and morphology of internal organs: experimental animal study

To evaluate the effect of NO added to the oxygenator during CPB on the liver and kidneys in pigs.Methods. The experiment was conducted on 10 pigs undergoing cardiac surgery using cardiopulmonary bypass (CPB). Animals of the experimental group (CPB-NO; n = 5) received NO with the gas mixture supplied to the oxygenator at 100 ppm. Animals of the control group (CPB-control; n = 5) did not receive NO via the oxygenator. The surgery lasted 4 hours and was followed by 12-hour postoperative monitoring. To assess the liver and kidney injury, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) were determined at baseline, at weaning from the CPB, 6 and 12 hours after weaning from the CPB. A pathomorphological study of the liver and kidneys was also performed.Results. A long period of CPB deliberately used in our experiment caused liver injury. In the CPB-control group, an increase in the ALT concentration was found: 43 (34; 44) U/l at baseline to 82 (53; 99) U/l 12 hours after CPB, p < 0.05. AST concentration in the CPB-control group increased from 25 (17; 26) U/l at baseline to 269 (164; 376) U/l 12 hours after CPB (p < 0.05). We found no significant increase in ALT and AST concentrations in the CPB-NO group. There were no significant differences in ALT and AST concentrations between CPB-NO and CPB-control groups at all study time points. In the CPB-control group, an increase in the creatinine level was found from 131 (129; 133) μmol/l at baseline to 273 (241; 306) μmol/l 12 hours after CPB (p < 0.05). We found no significant increase in creatinine levels in the CPB-NO group. Creatinine levels in the CPB-NO group were significantly lower than in the CPB-control group 12 h after weaning from CPB: 183 (168; 196) vs 273 (241; 306) μmol/l (p < 0.008). We found no significant differences between the study groups by the NGAL level. Morphology revealed characteristic alterative changes in tissues, circulatory disorders, and inflammatory infiltration of varying degrees of severity, which in combination is a manifestation of the acute damaging effect of CPB. In the CPB-NO group, the severity of pathological changes, measured in points, was lower than in the CPB-control group, but no statistically significant differences were found.Conclusion. NO added to the oxygenator gas mixture reduces liver and kidney injury during prolonged CPB. Further research is required.

Insight into the negative effect and lipid profile alterations in liver of mice exposed to methylimidazolium ionic liquids, a novel "green" solvent.

Ionic liquids (ILs) have been recognized as potential environmentally friendly solvents; however, their potential toxicity to living organisms warrants thorough investigation, particularly for novel-generation ILs in mammalian models. In this study, we examined the hepatic effects and disruption of lipid metabolism in mice exposed to 1-heptyl-3-methylimidazolium chloride (C7[MIM]Cl), a novel ILs. After four weeks of oral administration at different dosages (2.38, 5.95, and 11.9mg/kg b.w.), we conducted clinical chemistry analysis and histopathological examination of the liver to assess biochemical and structural changes. The low-dose C7[MIM]Cl group exhibited a significant increase in alanine aminotransferase (ALT) levels, while aspartate aminotransferase (AST) levels were elevated in both low-dose and high-dose groups without statistical significance. Histopathological examination showed inflammatory cell infiltration and red blood cell aggregation in the livers of mice exposed to C7[MIM]Cl, particularly in the high-dose group. Oxidative stress levels showed moderate changes in response to C7[MIM]Cl exposure. Notably, hepatic biochemical parameters revealed a dose-dependent increase in triglycerides (TG) levels with statistically significant differences compared to the control group (P≤0.01). Targeted lipidomic analysis revealed notable alterations in liver lipids of mice exposed to C7[MIM]Cl, with lysophosphatidylethanolamine (18:0), phosphatidylcholines (18:0), and phosphatidylcholines (19:0) identified as critical lipids associated with C7[MIM]Cl exposure. Furthermore, metabolic pathway analyses demonstrated significant disturbances in the glycerophospholipid metabolic pathway. These findings provide valuable insights into the hepatic effects of C7[MIM]Cl exposure and novel perspectives on the disruption of lipid metabolism underlying ILs toxicity.

Effect of COVID-19 on Liver Enzymes in Hospitalized COVID-19 Patients in the Gaza Strip: A Retrospective Study

In severe cases, the novel coronavirus disease 2019 (COVID-19) can cause respiratory failure and multiple organ dysfunction, including liver injury. This study assessed the COVID-19 effect on liver function among hospitalized COVID-19 patients. Three-hundred and seventy patients were recruited. Patients were distributed as the following: control group (n=100), intensive care unit (ICU) hospitalized COVID-19 patients (n=140), and non-ICU hospitalized COVID-19 group (n=130). Data about the levels of liver enzymes were collected from the hospital medical records of the participants. Our results showed a significant increase in alanine aminotransferase (ALT) levels among the ICU hospitalized COVID-19 patients compared with the non-ICU hospitalized COVID-19 patients (p-value <0.01) and the controls (p-value <0.001). Aspartate aminotransferase (AST) concentration significantly increased among the ICU-hospitalized COVID-19 group compared with the non-ICU hospitalized COVID-19 group (p-value <0.01) and the controls (p-value <0.05). The ICU-hospitalized COVID-19 patients had a higher increase in alkaline phosphatase (ALP) levels compared to the non-ICU hospitalized COVID-19 patients and controls (p values <0.001). Based on ALT, AST, and ALP levels, we found that 73 (52%), 77 (55%), and 38 (27%) of the ICU hospitalized COVID-19 patients developed a liver injury. Of those, 12 (8.5%) died compared to 5 (3.5%) patients with abnormal liver function. In conclusion, these findings suggest that COVID-19 disease is associated with abnormal liver function and liver injury.

Growth performance, liver and kidney functions, blood hormonal profile, and economic efficiency of broilers fed different levels of threonine supplementation during feed restriction

The objective of the existing investigation was to determine the effect of dietary inclusion of threonine amino acid at different levels during feed restriction on growth indices, liver and kidney function parameters, and some hormonal profiles along with economic indicators in broiler chickens. A total of 1,600 from 2 different breeds (800 Ross 308 and 800 Indian River) at 21-day-old age were incorporated. Chicks were randomly assigned into 2 main groups, control and feed-restricted (8 h/d), during the fourth week of age. Each main group was subdivided into 4 groups. The first group was fed a basal diet without adding extra threonine (100%), the second, third, and fourth groups were fed a basal diet with extra threonine levels of 110, 120, and 130%, respectively. Each subgroup consisted of 10 replicates of 10 birds. We noticed that the dietary inclusion of threonine at extra levels in the basal diets significantly enhanced final body weight, body weight gain, and better feed conversion ratio. This was mainly due to the enhanced levels of growth hormone (GH), insulin-like growth factor (IGF1), triiodothyronine (T3), and thyroxine (T4). Moreover, the lowest feed cost per kilogram body weight gain and improved return parameters were reported in control and feed-restricted birds fed higher levels of threonine than other groups. Also, a significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urea levels was observed in feed-restricted birds supplemented with 120 and 130% levels of threonine. Hence, we recommend supplementing threonine at levels of 120 and 130% in the diet of broilers to promote growth and profitability.

Evaluation of the Possible Protective Role of Nobiletin against Arsenic-Induced Liver Damage in Male Albino Rats.

Arsenic (As) is a toxic contaminant present in organic and inorganic forms in the environment. Nobiletin (NOB) is a polymethoxy flavone that has recently gained substantial consideration due to its curative impacts. The present experiment was conducted to assess the hepatoprotective efficiency of NOB on As-generated hepatotoxicity. Twenty-four adult rats were equally distributed into four groups and designated as control, As (50 mg/kg)-treated, As + NOB (50 mg/kg and 25 mg/kg, respectively), and NOB (25 mg/kg)-treated groups. After 30 days, experimental animals were decapitated, then blood and tissue samples were collected for further analysis. The group treated with As showed a significant decrease in the activity of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione (GSH), glutathione reductase (GSR), and total antioxidant status (TAS), and a substantial increase in the accumulation of As in liver tissues, levels of total oxidant status (TOS), hydrogen peroxide (H2O2), and lipid peroxidation (TBARS). Significant increases in alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) levels were observed in As-treated rats. Moreover, nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interleukin (IL)-6, and cyclo-oxygenase (COX)-2 activity, as well as the levels of pro-apoptotic markers (Bax, Caspase-3, and Caspase-9) were increased on exposure to As. In contrast, the anti-apoptotic marker (Bcl-2) level was significantly decreased. As administration showed a significant disturbance in hepatic tissue histology. However, cotreatment of NOB with As considerably increased the antioxidant enzyme activity, with a noteworthy reduction in the deposition of As in hepatic tissues, TBARS, and H2O2 levels. NOB-administrated rats showed considerable recovery in terms of inflammation, apoptosis, and histological damage. Hence, NOB can be considered a useful curative compound due to its medicinal properties against As-prompted hepatotoxicity.

Hepatoprotective effect of obeticholic acid on acetaminophen induced hepatotoxicity in mice

Acetaminophen (APAP) is commonly used as analgesic and antipyretic drug for relieving mild and moderate pain, but at high doses produces hepatic necrosis. Though, Obeticholic acid (OCA) has been tested in range of diseases, its therapeutic potential against APAP-induced hepatic injury remains to be elucidated. Thus, in this study, we investigated the preventive effect of OCA along with N-acetylcysteine (NAC) and Silymarin (SIL) against acetaminophen-induced hepatotoxicity in mice. SIL (100 mg/kg, po) and OCA (30 mg/kg, po) were administered continuously for six days prior to APAP administration. After sixth dose, animas were fasted for 12 h and treated with 300 mg/kg APAP and then received SIL (100 mg/kg, po), NAC (500 mg/kg, ip) and OCA (30 mg/kg, po) at 1 h after APAP. Mice were sacrificed 6 h after APAP injection. Analysis of serum Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), liver glutathione (GSH) and histopathology were employed for assessment of hepatotoxicity. APAP group showed a significant increase in ALT, AST, ALP and centriolobular hepatic necrosis with a significant decrease in glutathione in comparison to control group. All these parameters were significantly improved in all the three treated groups when compared to APAP group. In conclusion, Obeticholic acid (OCA), Silymarin (SIL) and N-acetylcysteine (NAC) are suggested to protect against APAP-induced hepatotoxicity in mice by ameliorating liver enzymes, antioxidant effect and decreasing liver necrosis.

Hepatoprotective and nephroprotective efficacy of Cichorium intybus following imidacloprid induced subchronic toxicity in WLH cockerels

The current research work was undertaken to evaluate the hepatoprotective and nephroprotective potential of Cichorium intybus following subchronic exposure of imidacloprid in white leghorn (WLH) chicks. Thirty, 6 to 8 weeks old chicks of 300-350 g weight were randomly and equally divided into five groups. Group I served as control and was fed normal grower ration and other were fed medicated ration containing Cichorium intybus leaf powder @ 5000 ppm in Group II, imidacloprid @ 100 ppm in Group III, imidacloprid @ 100 ppm + silymarin @ 100 ppm in Group IV and imidacloprid @ 100 ppm + Cichorium intybus leaf powder @ 5000 ppm in Group V, respectively, for 8 weeks. Biochemical parameters at 4th and 8th week revealed a significant increase in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, total bilirubin, indirect bilirubin, creatinine, blood urea nitrogen (BUN) with an increase in absolute and relative organ weights of liver and kidney after 8 weeks and a significant decline in total protein, albumin and globulin in imidacloprid treated Group III as compared to control (Group I). However, the simultaneous administration of Cichorium intybus leaf powder (CILP) in Group V revealed amelioration in these parameters at par with Groups I and IV. Thus, amelioration of imidacloprid induced hepatotoxic and nephrotoxic effects following simultaneous CILP administration indicates hepatoprotective and nephroprotective potential of Cichorium intybus in imidacloprid intoxicated cockerels.

Biochemical Evaluation of Laparoscopic Portoenterostomy for Treating Biliary Atresia and Redo for Failed Portoenterostomy.

Background: Postoperative outcomes of portoenterostomy (PE) and redo-PE were evaluated using selected biochemical markers (SBM) and biochemical status categories (BSC). Methods: Subjects were 70 consecutive PE performed for biliary atresia. SBM were aspartate aminotransferase (AST)/alanine aminotransferase (ALT), cholinesterase (ChE), and platelet count (PLT) assessed at 1, 2, 3, 6, and 12 months, and thence, annually for a maximum of 10 years. BSC were as follows: all SBM normal (N-SBM), normal AST/ALT (N-SLT), normal ChE (N-ChE), normal PC (N-PLT), all abnormal (A-SBM), abnormal AST/ALT (A-SLT), abnormal ChE (A-ChE), and abnormal PC (A-PLT). Subjects achieving jaundice clearance (JC) and surviving with native livers (SNL) also had gamma glutamyl transpeptidase assessed. Redo-PE indicated for failed PE was assessed postoperatively using the same SBM/BSC protocol. Results: PE were laparoscopic (LPE; n = 40) or open (OPE; n = 30). Mean age/weight at PE and duration of follow-up were similar. For JC, LPE = 34/40 (85.0%) and OPE = 22/30 (73.3%); P = .23. For SNL, LPE = 29/40 (72.5%) and OPE = 16/30 (53.3%); P = .10. LPE and OPE were similar for SBM/BSC, except for a single significant increase in ALT in OPE at 6 months. Redo-PE was performed 17-180 days (mean 67.1 days) after primary PE. AST was significantly increased at the last preredo assessment 3 months after primary PE; P < .05. After redo, AST decreased and SBM/BSC results were equivalent to nonredo subjects. Conclusion: Postoperative biochemical data for all PE cases were comparable; redo-PE would appear to be viable for restoring SBM, and AST could be valuable as a single marker of deterioration in redo cases.

Protective Effects of Quercetin on Clothianidin-Induced Liver Damage in the Rat Model.

Clothianidin (CTD) is a member of the neonicotinoid group of insecticides. This study was performed to determine the effect of quercetin on clothianidin-induced liver injury (CTD) in rats. Rats were randomly assigned to a normal control (saline), a CTD control-treated group (20 mg/kg) every 3 days for 21 days, and CTD + quercetin-treated groups (2.5, 5, and 10 mg/kg) for 35 days intraperitoneally. Enzyme activity, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), was measured by spectrophotometry in serum samples by an automatic biochemical analyzer using commercial kits. Total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrate-nitrite were measured in homogeneous liver tissue samples of animals. A significant increase in ALT and AST enzyme activity was observed in the CTD group in comparison with that of the control groups. In the clothianidin + quercetin (10 mg/kg) group, the ALT and AST enzyme levels decreased compared to the clothianidin control group significantly (P < 0.05). The MDA value of the liver increased in the clothianidin-treated group compared to that of the control groups (P < 0.05). Decreased tissue TAC level was observed in the CTD-treated group in comparison with that of the control groups (P < 0.05). The MDA level of the liver decreased in the clothianidin + quercetin (10 mg/kg) group compared to that of the CTD control group (P < 0.05). Quercetin significantly raised the level of TAC in the liver tissue of the clothianidin + quercetin (10 mg/kg) treated group compared to that of the clothianidin control group (P < 0.05). Liver nitrate-nitrite measurement showed a significant increase in the clothianidin group compared to that of the normal control group (P < 0.05). Nitrate-nitrite level in the liver was decreased in clothianidin + quercetin (10 mg/kg) compared to that of the clothianidin control group significantly (P < 0.05). Histopathological investigation revealed that contact to the CTD induced tissue disorganization and inflammatory cell infiltration, but minor histopathological alterations in the liver tissues of rats treated with CTD and quercetin (10 mg/kg) were detected.

Pumpkin seed oil and zinc attenuate chronic mild stress perturbations in the cerebral cortex of rats

PurposeThis study aims to investigate the potential of pumpkin seed oil (PSO) and zinc to attenuate oxidative stress and neuroinflammation caused by chronic mild stress (CMS) in the cerebral cortex of male rats.Design/methodology/approachThe rats were submitted to stress for six weeks and then the behavior of the rats was tested by forced swimming test (FST) and novel cage test. The treated groups were given venlafaxine (20 mg/kg), pumpkin seed oil (40 mg/kg) and zinc (4 mg/kg). The cortex homogenate was used for the detection of the oxidative stress parameters, the concentration of neurotransmitters, tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β), Na+/K+-ATPase activity, and the expression of histamine N-methyltransferase (Hnmt) and tyrosine hydroxylase (Th).FindingsCMS causes a significant increase in immobility time in the FST and a significant decrease in the number of rearing in the novel cage test. CMS group showed a significant increase in alanine aminotransferase (ALT) activity, levels of cortisol, TNF-α, IL-1β, nitric oxide and malondialdehyde. CMS caused a significant decrease in the concentrations of serotonin, GABA, norepinephrine, and the activities of glutathione peroxidase, catalase, superoxide dismutase and Na+/K+-ATPase. CMS caused a marked reduction in the expression of Hnmt and Th in the cortex. PSO and zinc attenuated the Na+/K+-ATPase activity, oxidative parameters and neuroinflammation induced by the CMS, and this was reflected by the elevation of the concentration of neurotransmitters and reduction of cortisol and ALT, in addition to the behavior normalization. PSO and zinc attenuated the CMS by improving the antioxidant milieu and anti-inflammatory status of the cerebral cortex.Originality/valueThere are no studies on the effect of pumpkin seed oil on depression

Ethanol Extract of Myrtle (Myrtus communis L.) Berries as a Remedy for Streptozotocin-Induced Oxidative Stress in Rats.

Streptozotocin (STZ) is an antitumor antibiotic indicating in the treatment of metastatic islet cell carcinoma of the pancreas. It is also used as a tool to create experimental diabetes models. The STZ exposure at a high dose causes severe damage to cells of humans and other mammals. The goal of the present study was to assess the protective effects of the ethanol extract of the Myrtle (Myrtus communis L.) berries, which is a well-known medicinal plant due to its rich phenolic content and beneficial effects on health, against STZ-induced oxidative stress in the diabetic rats.Diabetes was induced by STZ (40mg/kg, i.p.) in the rats. After diabetes induction, a significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), and blood glucose levels as well asa significant decrease in superoxide dismutase (SOD) activities and glutathione (GSH) levels was observed. The rats were treated to three different ethanol extracts of Myrtle berries (0.25, 0.5, and 1g/kg) by oral gavage for 14days. At the end of the experiment, ALT, AST, MDA, and blood glucose levels of the rats significantly decreased while significant increases in GSH levels and SOD activities were observed.We believe that our findings may contribute to the development of new drugs in the treatment of many global disorders due to the antioxidant activity of the ethanol extract of Myrtus communis L. berries.

Evaluation ofFoeniculum vulgareimpact on glyphosate hepato‐toxicity in Nile tilapia: Biochemical, molecular and histopathological study

Glyphosate, a common herbicide widely used all over the world, can reach the aquatic environment and adversely affect their living organisms. The current study was designed to investigate the possible ameliorating effect of Foeniculum vulgare (Fennel) against glyphosate exposure in Nile tilapia. The fish in this study were assigned into six groups: Control group, Fennel 1 group and Fennel 2 group: fed on 1 and 2 ml/kg diet, respectively, Glyphosate group: exposed to 1.2 ± 0.05 mg/L glyphosate in water, Glyphosate + Fennel 1 group and Glyphosate + Fennel 2 group: exposed to glyphosate and fed on fennel supplemented diet, all for 30 days. Blood and tissue samples were collected from all groups at the end of the experiment. The biochemical analysis of serum revealed a significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities after glyphosate exposure. Moreover, a profound state of hepatic oxidative stress was observed in fish exposed to glyphosate as an increase in malondialdehyde and DNA fragmentation and a decrease in antioxidant enzyme activities. The gene expression of hepatic pro-inflammatory cytokines (Tumour necrosis factor-α–Interleukin-1β) was up-regulated in the glyphosate group. On the other hand, a diet supplemented with fennel extract reversed to a large extent the above-mentioned adverse effects of glyphosate exposure in a dose-dependent manner. Therefore, we could conclude that fennel supplementation provides a natural, safe and economically available method to reverse and protect against the inevitable pesticide exposure in non-target organisms as Nile tilapia.

The protective effect of p-coumaric acid on toluene-induced hepatotoxicity, nephrotoxicity and neurotoxicity in rats

Objective. The aim of this study was to determine the protective effect of p-coumaric acid (p-CA) against toluene-induced hepatotoxicity, nephrotoxicity and neurotoxicity in rats. Materials and methods. A total of 32 Sprague-Dawley male rats, 8 in each group, were used. 4 groups were formed as control, toluene, p-CA and toluene+p-CA. Animals in the control group, toluene group and p-CA group were given 0.9% NaCl, 0.9 mg/kg b.w toluene and 100 mg/kg b.w p-CA orally for 21 days, respectively. The animals in toluene+p-CA group were received p-CA for 3 days and from day 4, toluene and p-CA were applied together daily until day 25. On the 25th day, the study was terminated, blood and tissue samples were collected. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine levels in serum, glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) and glutathione (GSH) levels in the tissue samples were determined. Results. In this study, it was determined that there were significant increases in ALT and AST activities, and creatinine levels in toluene-induced group compared to control group. Moreover, there was a decrease in the GSH-Px activities and GSH levels, and an increase in the MDA levels compared to the control group. However, in the toluene+p-CA group, significant decreases in aminotransferases activities, creatinine and MDA levels, and significant increases in GSH-Px activities and GSH levels were determined compared to the toluene group. Conclusions. It has been determined that p-CA has a protective effect against toluene-induced hepatotoxicity, nephrotoxicity and neurotoxicity.

Protective Effects of Delonix regia Leave Extract on Sodium Arsenite-Induced Hepatotoxicity in Rats

Nature provides rich sources of structurally diverse phytochemicals with medicinal relevance and biological activities. Sodium arsenite has been recognized as a worldwide health concern due to its teratogenicity effects on animals. Natural plants are considered as a possible protective agent against arsenic induced toxicity. The aim of this study was to investigate the protective effects of Delonix regia leave extracts on sodium arsenite induced hepatotoxicity in rat. Animals were randomly divided into six groups of five per group. Group A (control) received distilled water for fourteen (14) days. Group B received 2.5 mg/kg body weight Sodium Arsenite, group C received 100 mg/kg of leave extract and 2.5 mg/kg of sodium arsenite, Group D received 400 mg/kg of leave extract and 2.5 mg/kg of sodium arsenite, Group E received 100 mg/kg of leave extract, Group F received 400 mg/kg of leave extract only. On the fourteen day all the animals were sacrificed. Biochemical parameters such as plasma Alanine amino transferase (ALT), Aspartate amino transferase (AST) Alkaline phosphate (ALP) and gamma glutamyl transferase (GGT) total protein (TP) were evaluated. Sodium arsenite in rat triggers significant increase in ALT, AST, ALP, TP, and GGT (p<0.05 level). Upon treatments with Delonix regia leave extract, it decreases the concentration of GGT, AST and ALP compared to the negative control. Group treated with the extract alone showed no adverse effects on the liver parameters. Results from this study suggest that, the administration of Delonix regia leave extract confer some protective effects on the liver.

Liver function recovery of COVID-19 patients after discharge, a follow-up study.

Objective: The aim of this study was to observe the liver function recovery of COVID-19 patients after discharge.Patients and Methods: A total of 253 discharged COVID-19 patients in Shenzhen city, China were selected. The clinical characteristics of these patients were assessed. A 2-month follow-up and laboratory hematology test were performed to examine the status of patients' liver function.Results: Patients combined with liver diseases, especially fatty liver, are more likely to progress to severe condition (P<0.05). Patients in severe condition and those with liver diseases have higher rates of liver injuries during hospitalization, characterized by a significant increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P<0.01). The ALT, AST/ALT, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), and A/G levels showed significant differences in comparison with the control group (P<0.05, and P<0.001); and the outlier ratio of A/G, ALT, GGT and ALP of patients remained abnormal higher within 14 days after discharge (P<0.001). Liver injuries of COVID-19 patients may be related to the epidemiological characteristics, clinical indexes, basic diseases, symptoms, drug treatment during hospitalization and the complications. Indicators of liver function were correlated with cardiac function, renal function, thyroid function, lipid metabolism, glucose metabolism, immune index, leukocyte, erythrocyte, hemoglobin and platelet related indexes. The outlier ratio of TP, ALB and GLB remained extremely low throughout the follow-up period; the outlier ratio of ALT, AST and GGT decreased below 10% from a high level at 40 days after discharged. However, the outlier ratio of A/G, AST/ALT and ALP remained high during the follow-up period.Conclusions: Abnormal liver function might indicate worse recovery of COVID-19 patients. Changes in liver function should be emphasized during long-term follow-up of COVID-19 patients after hospital discharge; the necessity of employing appropriate interventions for liver function repair should be emphasized.

Investigation of anti-inflammatory effects of bee venom in experimentally induced adjuvant arthritis.

ObjectivesRheumatoid arthritis is a multisystemic inflammatory disease characterized by destruction of the joints. An effective treatment method of the disease has not been developed yet. The aim of the present study is to evaluate the effects of bee (Apis mellifera anatoliaca) venom (BV) on serum inflammatory parameters, serum antioxidant load and clinical parameters of experimentally induced adjuvant arthritis in rats.Material and methodsA total of 35 Wistar albino male rats were used. The animals were divided into 5 groups. First group animals served as negative controls. The second, third, fourth and fifth groups were used for experimental arthritis induction. Following clinical development of arthritis, the first group was subcutaneously administered 0.2 ml of physiological saline, and the second, third and fourth groups were treated subcutaneously with 2 µg/kg, 4 µg/kg and 20 µg/kg once a week three times. Physiological saline injected fifth group animals were used as a sham-treatment group. Clinical observations and evaluation of arthritis were made at the 15th day, and at the end of the experiment. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, paraoxonase, serum aryl esterase, high-sensitivity C reactive protein, interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) were determined in cardiac blood samples taken at the end of the 29th day.ResultsFrom the data, total oxidant level (TOL) and oxidative stress index (OSI) were calculated. Significant improvements were observed in the clinical signs of arthritis and inflammatory markers such as in IL-1β, TNF-α, IL-6 and TOL and OSI in the 20.0 µg/kg BV-administered group. Bee venom administration did not cause any significant increase in ALT and AST values or signs of liver toxicity.ConclusionsBee venom treatment was effective in alleviation of symptoms of the experimental rat adjuvant arthritis by means of clinical observation and serum inflammatory markers.