Sildenafil, a phosphodiesterase-5 inhibitor, offers protection against carbon tetrachloride-induced hepatotoxicity in rat

2018 ◽  
Vol 29 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Olorunfemi R. Molehin ◽  
Anne A. Adeyanju ◽  
Stephen A. Adefegha ◽  
Oluwasanmi O. Aina ◽  
Blessing A. Afolabi ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Selective Inhibition ◽  
Guanosine Monophosphate ◽  
Control Group ◽  
Gamma Glutamyl Transferase ◽  
Protective Agent ◽  
Glutamyl Transferase ◽  
Phosphodiesterase 5

AbstractBackground:Elevation of phosphodiesterase-5 (PDE5) activity converts cyclic guanosine monophosphate (cGMP) to 5′-GMP, a mechanism that could be associated with drug-mediated hepatotoxicity. This study investigated whether selective inhibition of PDE5 by sildenafil could offer protection against hepatotoxicity induced by carbon tetrachloride (CCl4).Methods:CCl4(0.5 mL/kg) was administered intraperitoneally to induce hepatotoxicity. The control group received normal saline. Sildenafil (5 mg, 10 mg, and 20 mg/kg, p.o.) was administered to CCl4-treated rats.Results:CCl4significantly increased the serum levels of gamma glutamyl transferase (γ-GT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and reduced total protein (TP) (p<0.05). Pretreatment with sildenafil moderately reduced ALP, AST, and ALT activities with modest increase in TP level. CCl4-induced changes in the antioxidant status of the liver were significantly improved by sildenafil, especially at the lowest dose of 5 mg/kg by elevating the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) and preventing lipid peroxidation (p<0.05). Sildenafil did not significantly alter the total cholesterol and triglyceride levels. However, high-density lipoprotein (HDL) level was significantly increased by sildenafil (p<0.05).Conclusions:The results from this study suggest that sildenafil, when used at low doses, may be a useful pharmacological protective agent against CCl4-induced hepatotoxicity.

scholarly journals Manganese Inhibits Indomethacin-Induced Hepatorenal Oxidative Stress in Wistar Rats

2020 ◽  
pp. 79-90
Author(s):  
Tijani Stephanie Abiola ◽  
Olori Ogaraya David ◽  
Farombi Ebenezer Olatunde
Keyword(s):  
Oxidative Stress ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Control Group ◽  
Gamma Glutamyl Transferase ◽  
Cellular Processes ◽  
Concomitant Reduction ◽  
Liver And Kidney ◽  
Glutamyl Transferase ◽  
And Oxidative Stress

Aim: Manganese (Mn) is an essential trace element in many cellular processes. However, there is dearth of literature on its influence on indomethacin-induced hepatorenal damage. Therefore, this study was conducted to investigate the effect of manganese on indomethacin-induced hepatorenal damage in rats. Methods: Rats were divided into four groups of eight rats consisting of control group, indomethacin (IND) alone (20 mg/kg), Mn alone (10 mg/kg) and co-treated group that were treated orally for 14 consecutive days. Twenty four hours after treatment, under pentobarbital anesthesia, blood was collected and liver was excised to prepare homogenate and histology staining. Liver and kidney function tests aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), glutamine dehydrogenase (GLDH), sorbitol dehydrogenase (SDH), glucose-6-phosphate dehydrogenase (G6PD), bilirubin (BIL), urea, creatinine, cholesterol (CHOL), triglycerides (TG), low and high density lipoprotein (LDL and HDL), electrolytes and oxidative stress superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and lipid peroxidation (LPO) biomarkers were assessed. Results: The results showed that indomethacin caused hepatorenal damage in rats manifested with increase in serum hepatic and renal function biomarkers. But co-administration of IND with Mn significantly (p < 0.05) decreased the level of hepatorenal biomarkers. Additionally, co-administration of IND with Mn improved the antioxidant status with concomitant reduction of LPO and restored the integrity of the liver and kidney histologically. Conclusion: The results of this study emphasize that co-administration of IND with Mn to rats alleviated IND-induced hepatorenal toxicities and oxidative stress in rats.

scholarly journals Hepatotoxic Assessment of Tramadol-Diclofenac Use: A Study in a Rat Model

2019 ◽  
Vol 8 (2) ◽  
pp. 41-45
Author(s):  
Elias Adikwu ◽  
Ebinyo Clemente Nelson
Keyword(s):  
Density Lipoprotein ◽  
Serum Levels ◽  
The Body ◽  
Albino Rats ◽  
Gamma Glutamyl Transferase ◽  
Cholesterol Levels ◽  
Concurrent Use ◽  
Hepatotoxic Effect ◽  
Hepatocyte Necrosis ◽  
Glutamyl Transferase

The concurrent use of tramadol and diclofenac may increase hepatotoxic risk due to their individual hepatotoxic effects. This study assessed the hepatotoxic effect of tramadol-diclofenac administration in albino rats. Twenty-four adult male albino rats (200-220g) randomized into four groups were orally administered with tramadol (12mg/kg/day), diclofenac (6mg/kg/day) and tramadol-diclofenac for 14 days respectively. The rats were anesthetized, blood samples were collected and evaluated for serum liver function and lipid parameters. Liver samples were weighed and evaluated for biochemical parameters and histology. The effects of tramadol-diclofenac on the body and liver weights did not differ significantly (p>0.05) when compared to control. Also, effects were not significant (p>0.05) on blood glucose, and serum cholesterol, triglyceride, low and high density lipoprotein cholesterol levels when compared to control. Liver and serum levels of aminotransferases, alkaline phosphatase, lactate dehydrogenase, gamma–glutamyl transferase, conjugated bilirubin and total bilirubin increased significantly in rats treated with tramadol (p<0.05), diclofenac (p<0.01) and tramadol-diclofenac (p<0.001) when compared to control. Furthermore, significant decreases in liver catalase, glutathione, superoxide dismutase, glutathione peroxidase levels with significant increases in malondialdehyde levels occurred in rats treated with tramadol (p<0.05), diclofenac (p<0.01) and tramadol-diclofenac (p<0.001) when compared to control. Hepatocyte necrosis was observed in rats treated with tramadol-diclofenac. Tramadol-diclofenac may increase hepatotoxic risk at doses used for this study.

scholarly journals Hypolipidemic effect of azima tetracantha on lipid profile markers of carbon tetrachloride induced liver toxicity in rats

2019 ◽  
Vol 10 (3) ◽  
pp. 2104-2108
Author(s):  
Saleem K ◽  
Nargis Begum T ◽  
Muhammad Ilyas MH
Keyword(s):  
Carbon Tetrachloride ◽  
Lipid Profile ◽  
Liver Toxicity ◽  
Density Lipoprotein ◽  
Control Group ◽  
Hypolipidemic Effect ◽  
Protective Agent ◽  
Serum Triglycerides ◽  
Reference Drug ◽  
Azima Tetracantha

This study was aimed at evaluating the hypolipidemic effects of ethanolic extract of Azima tetracantha leaves against liver toxicity induced by carbon tetrachloride (CCl4) in male albino Wistar rats and to compare the same with the reference drug silymarin. Six groups of rats with six rats in each group were used as the experimental subject. Animals were allocated into a control group and liver toxicity control group. The remaining four groups received in addition to CCl4, silymarin (20 mg/kg/d) as a reference treatment and Azima tetracantha (100, 200 and 400mg/kg/d). Once the experiment period was completed, the biomarkers of lipid profile, including total cholesterol, serum triglycerides, high-density lipoprotein (HDL) and low-density lipoprotein (LDL)] were evaluated. Azima tetracantha significantly decreased the serum lipid profile markers cholesterol, triglycerides, phospholipids, fatty acids, VLDL, LDL, and increased HDL. Azima tetracantha could be a promising protective agent against cholesterol through the improvement of liver function, modulation of CCl4 by-products formation and thus has hypolipidemic potentials.

Ameliorative effect of trimetazidine on cisplatin-induced hepatotoxicity in rats

2016 ◽  
Vol 94 (2) ◽  
pp. 225-230 ◽  
Author(s):  
Hayam Ateyya ◽  
Hala Yosef ◽  
Manar A. Nader
Keyword(s):  
Liver Damage ◽  
Antioxidant Defense System ◽  
Serum Levels ◽  
Control Group ◽  
Gamma Glutamyl Transferase ◽  
Protective Effects ◽  
Bax Protein ◽  
Ameliorative Effect ◽  
Glutamyl Transferase ◽  
Per Oral

This study was designed to evaluate the protective effects of trimetazidine (TMZ) against cisplatin (CP) induced liver damage in rats. Animals were distributed among 4 groups as follows: control group; TMZ group (20 mg/kg body mass, per oral), which was treated for 10 days; CP group (6 mg/kg, by intraperitoneal injection), which received a single injection; and the CP + TMZ group (20 mg/kg, per oral), which received TMZ 4 days before and 6 days after CP injection. The extent of hepatic damage was studied by assessing biochemical parameters and histopathological evaluation of the extracted liver tissue. The results revealed that liver enzymes were markedly elevated after injection of CP, as evident from significant increases in the serum levels of alanine transaminase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (γ-GT), and lactate dehydrogenase (LDH), as well as marked changes to the liver architecture, with a significant decrease in serum levels of albumin. There were also marked changes to the antioxidant defense system, as indicated by significant decreases in total antioxidants and hepatic levels of reduced glutathione (GSH) and superoxide dismutase (SOD), together with a significant increase in lipid peroxidation. However, there was a significant increase in the activity of hepatic nuclear factor kappa B (NF-κB) as well as hepatic Bax protein expression. We conclude that TMZ protects against CP-induced liver damage through scavenging free radicals and anti-inflammatory and antiapoptotic effects, as well as through reducing NF-κB activation.

scholarly journals Antioxidant and Hepatoprotective Effects of Methanolic Extracts of Zilla spinosa and Hammada elegans Against Carbon Tetrachlorideinduced Hepatotoxicity in Rats

2018 ◽  
Vol 16 (1) ◽  
pp. 133-140 ◽  
Author(s):  
Riaz Ullah ◽  
Mansour S. Alsaid ◽  
Abdelaaty A. Shahat ◽  
Almoqbil Abdulaziz Naser ◽  
Abdullah A. Al-Mishari ◽  
...  
Keyword(s):  
Liver Toxicity ◽  
Unmet Need ◽  
Serum Levels ◽  
Control Group ◽  
Gamma Glutamyl Transferase ◽  
Methanolic Extracts ◽  
Group 5 ◽  
Group 2 ◽  
Glutamyl Transferase ◽  
Antioxidant Effects

AbstractThe detoxification, metabolism, and excretion of various endogenous and exogenous materials occur mainly in the liver. Liver diseases are a global concern, and classified as chronic hepatitis, cirrhosis, and hepatosis. The development of safe hepatoprotective agents remains an unmet need. Therefore, we investigated the antioxidant effects of methanolic and n-hexane fractions of Zilla spinosa (ZSM and ZSH, respectively) and Hammada elegans (HEM and HEH, respectively) against carbon tetrachloride (CCl4)-induced liver toxicity in rats. Antioxidant activity was studied by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The rats were divided into 11 groups (n=6)–group, 1 (control), group 2 (CCl4 only), group 3 (CCl4+silymarin 10 mg/kg), group 4 (CCl4+HEM 250 mg/kg), group 5 (CC14+HEM 500 mg/kg), group 6 (CCl4+HEH 250 mg/kg), group, 7 (CCl4+HEH 500 mg/kg), group, 8 (CCl4+ZSM 250 mg/kg), group 9 (CCl4+ZSM 500 mg/kg), group 10 (CCl4+ZSH 250 mg/kg), and group 11 (CCl4+ZSH 500 mg/kg). Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, and total bilirubin were measured. The extent of hepatic injury was histopathologically assessed. Treatment with ZSM and ZSH at 250 and 500 mg/kg did not significantly affect biochemical results compared with the CCl4 only group. However, treatment with both HEM and HEH at 250 and 500 mg/kg provided significant (p<0.001) results compared with the CCl4 only group. These results were consistent with histological findings. HEM and HEH at 250 μg/mL significantly inhibited DPPH radical formation by 38.E6 and 35.65%, rerpectively. However antioxidant effects of ZSM and ZSH were insignificant.

scholarly journals Effect of Tannin-Rich Extract of Chasmanthera dependens on Piroxicam-induced Liver Damage in Male Wistar Rats

2021 ◽  
Vol 5 (1) ◽  
pp. 27
Author(s):  
Tijani Stephanie Abiola ◽  
Olori Ogaraya David ◽  
Farombi Ebenezer Olatunde
Keyword(s):  
Oxidative Stress ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Significant Rise ◽  
Control Group ◽  
Gamma Glutamyl Transferase ◽  
Male Wistar Rats ◽  
Anti Inflammatory ◽  
Group 2 ◽  
Glutamyl Transferase

Background: Piroxicam is one of the nonsteroidal anti-inflammatory drugs used as antipyretic, analgesic and anti-inflammatory drug often used for the relief of nonspecific fever condition and in arthritis. This study investigated the protective potential of tannin-rich extract of Chasmanthera dependens (TRECDS) against piroxicam-induced hepatotoxicity in male Wistar rats.Materials and Methods: Thirty two rats were divided into four groups. Group 1 received normal saline and served as the control group, group 2 were given 20 mg/kg piroxicam only, while groups 3 and 4 were given 20 mg/kg piroxicam with the addition of 200 and 400 mg/kg of tannin-rich extract of Chasmanthera dependens, respectively. All rats were treated orally once daily for ten days.Results: Administration of piroxicam caused liver atrophy demonstrated by significant rise in serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), glucose-6-phosphate dehydrogenase (G6PDH) levels of albumin (ALB), bilirubin (BIL), total cholesterol (TCHOL), triglyceride (TRIGS) and low-density lipoprotein (LDL). Piroxicam also decreased high-density lipoprotein (HDL) level, enzymatic and nonenzymatic antioxidant levels significantly (p>0.05) with attendant increase in oxidative stress indices in the liver of rats compared with control group. Histological assessment reveled severe damaged to the liver of rats. However, co-administration with TRECDS reversed these observations as evidenced in the histological results.Conclusion: The findings of this study showed that exposure of rats to piroxicam provoked damage to the liver via oxidative damage and TRECDS has the potential of ameliorating the damage.Keywords: hepatotoxicity, piroxicam, Chasmanthera dependens, oxidative stress

scholarly journals GAMMA-GLUTAMYL TRANSFERASE AS AN INDICATOR OF OBESITY: A CROSS-SECTIONAL STUDY

2016 ◽  
Vol 9 (9) ◽  
pp. 240
Author(s):  
Vinodhini V M ◽  
Sudhan Kb
Keyword(s):  
Insulin Resistance ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Hepatic Insulin Resistance ◽  
Control Group ◽  
Gamma Glutamyl Transferase ◽  
Gamma Glutamyl ◽  
Elevated Liver Enzymes ◽  
The Mean ◽  
Glutamyl Transferase

ABSTRACTObjective: Obesity, characterized by an increase in excessive fat accumulation, represents a social problem worldwide and has been recognizedas a major underlying factor in the pathogenesis of several diseases. Gamma-glutamyl transferase (GGT) is a cell-surface protein contributing tothe extracellular catabolism of glutathione. Elevated GGT is strongly associated with obesity and excess deposition of fat in the liver, termed nonalcoholicfatty liver disease, which is thought to cause hepatic insulin resistance and contribute to the development of systemic insulin resistanceand hyperinsulinemia. Therefore, we have investigated the serum GGT levels in obese individuals and the correlation of serum GGT with bodymass index (BMI) and waist circumference.Methods: The study was carried out in 100 obese patients and 100 non-obese individuals.Results: Patients with obesity showed a significant increase in GGT levels when compared to the control group. The mean levels of BMI, WC, totalcholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-c), very LDL-cholesterol, total protein, and aspartate aminotransferase werefound to be significantly elevated in the obese individuals compared to controls. The mean levels of high-density lipoprotein-cholesterol showed asignificant decrease in the obese participants.Conclusion: Elevated liver enzymes, although in normal ranges, especially at upper quartiles as observed in our study, may play a central role inearly diagnosis of fat overflow to the liver. The findings of our study suggest that serum GGT levels may be a simple and reliable marker of visceral fataccumulation.Keywords: Diabetes mellitus, Gamma-glutamyl transferase, Insulin resistance, Metabolic syndrome, Obesity.

l-Carnitine-induced amelioration of HFD-induced hepatic dysfunction is accompanied by a reduction in hepatic TNF-α and TGF-β1

2018 ◽  
Vol 96 (6) ◽  
pp. 713-725 ◽  
Author(s):  
Mabrouk Attia Abd Eldaim ◽  
Fatma Mohamed Ibrahim ◽  
Saher Hassan Orabi ◽  
Azza Hassan ◽  
Hesham Saad El Sabagh
Keyword(s):  
Protein Expression ◽  
High Density Lipoprotein ◽  
Body Mass ◽  
Density Lipoprotein ◽  
Basal Diet ◽  
Serum Levels ◽  
High Density ◽  
Control Group ◽  
Tnf Α ◽  
Tgf Β1

In this study, we evaluated the possible mechanisms through which l-carnitine ameliorates the adverse effects from obesity in rats, induced with a high-fat diet (HFD). For this, 56 albino Wister rats were randomly assigned to 7 groups. The control group was fed a basal diet and injected with saline. The second group was fed the basal diet and injected with l-carnitine (200 mg/kg body mass, by intraperitoneal injection; i.p.). The third group were fed the HFD. The fourth group was fed the HFD and injected with l-carnitine (200 mg/kg body mass, i.p.) for 8 weeks. The fifth group was fed the HFD for 10 weeks. The sixth group were fed the HFD for 10 weeks and were also injected with l-carnitine (200 mg/kg body mass, i.p.) during the final 2 weeks. The seventh group was fed the HFD diet for 8 weeks then the basal diet for 2 weeks. The HFD induced significantly increased levels of hyperglycemia, lipid peroxidation, pathological changes, TNF-α and TGF-β1 protein expression in hepatic tissue, food intake, body weight gain, serum levels of total and non-high-density lipoprotein cholesterol, ketone bodies, triacylglycerol, urea, creatinine, AST, and ALT. However, the HFD diet significantly decreased serum levels of high-density lipoprotein (HDL) and hepatic levels of reduced glutathione. l-Carnitine ameliorated the effects of the HFD on the above-mentioned parameters. This study indicated that l-carnitine had protective and curative effects against HFD-induced hepatosteatosis by reducing hepatic oxidative stress and protein expression of TNF-α and TGF-β1.

Correlation between Serum and Tissue Levels of Adipokines in Obesity in Adult Male Rats with and without Antioxidant

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M M Elshawwa
Keyword(s):  
Insulin Resistance ◽  
Adult Male ◽  
Fasting Glucose ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Lipoprotein Cholesterol ◽  
Male Rats ◽  
Control Group ◽  
Tissue Levels ◽  
Group I

Abstract Background Obesity is associated with insulin resistance, type2 diabetes, dyslipidemia and cardiovascular diseases. Apelin and chemerin are identified as adipokines and adipose tissue markers. Several adipose-derived peptides are known to influence food intake, including apelin, whose expression is regulated by insulin and chemerin. Oxidative stress thought to be involved in the development of complications associated with obesity. Objective To study the nature of correlation between serum and liver levels of apelin, chemerin and oxidative parameters in obese rats with and without antioxidant. Aiming to clarify the pathophysiology of obesity. Material and Methods Thirty adult male albino rats, divided into three equal groups. Group I (control), group II (obese) and group III (obese and Lepidium sativum (LS) as an antioxidants). At the end of the experiment, blood samples were collected for estimation of the serum levels of chemerin, apelin, fasting glucose, insulin, insulin resistance (IR), lipid profile, reduced glutathione (GSH) and malondialdehyde (MDA). In addition to tissue homogenous extracts of liver were taken for the levels of MDA, CAT, chemerin and apelin. Results After eight weeks, high fat diet group showed a significant increase in serum levels of apelin, chemerin, fasting glucose, insulin, IR, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) & MDA and a significant decrease in high-density lipoprotein cholesterol (HDL-C) & GSH. HFD also caused a significant increase in tissue levels of MDA, CAT & chemerin and a significant decrease in apelin, compared to control group. While addition of LS to HFD caused a significant decrease in serum levels of apelin, chemerin, fasting glucose, insulin, IR, TC, TG, LDL-C & MDA and a significant increase in HDL-C & GSH. LS also caused a significant decrease in tissue levels of MDA, chemerin & insignificant decrease in CAT and a significant increase in apelin, compared to HFD group. Conclusion This study showed a significant positive correlation between liver & serum chemerin and between liver and serum MDA. On the other hand, it showed a significant negative correlation between liver and serum apelin and liver CAT and serum GSH

scholarly journals PROTECTIVE ROLE AND ANTIOXIDANT ACTIVITY OF AQUEOUS EXTRACT OF ROSMARINUS OFFICINALIS AGAINST TRICHLOROACETATE-INDUCED TOXICITY IN LIVER OF MALE RATS

2018 ◽  
Vol 11 (6) ◽  
pp. 420
Author(s):  
Medhat Mostafa Abozid ◽  
Hoda Ea Farid
Keyword(s):  
Aqueous Extract ◽  
Liver Damage ◽  
Protective Role ◽  
Rosmarinus Officinalis ◽  
Male Rats ◽  
Control Group ◽  
Albino Rats ◽  
Gamma Glutamyl Transferase ◽  
Group I ◽  
Glutamyl Transferase

 Objective: The current study was designed to estimate the potential protective role of the aqueous extract of rosemary (AER) (Rosmarinus officinalis) against trichloroacetic acid (TCA)-created hepatotoxicity in male albino rats.Methods: Forty male albino rats were separated into four groups of ten: Group I served as control; Group II was given AER (200 mg/kg/day) by gavage; Group III received TCA at the dose 50 mg/kg/day, and Group V was treated with AER (200 mg/kg/day) and received TCA (50 mg/kg/day). The experiment was carried out for 2 months.Results: The toxicity of TCA for rats was revealed by an elevation in liver marker enzymes activities (gamma-glutamyl transferase [GGT], alkaline phosphatase [ALP], aspartate transaminase [AST], alanine aminotransferase [ALT]) and conjugated bilirubin (CB) level, and a decrease in albumin and total protein (TP) levels. The TCA administration also caused a significant increase in the activities of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), and also malondialdehyde (MDA) level in liver tissues. These biochemical effects were accompanied by histological indicators of liver damage. Treatment with ARE recovered the liver damage instigated by TCA, as showed by perfection of liver enzyme markers (GGT, ALT, AST, ALP), CB, TP and albumin; as well as antioxidant parameters (CAT, SOD, GPx) and lipid peroxidation (MDA) and amelioration of histopathology changes in the liver tissues.Conclusion: It could be concluded that AER supplementation for 2 months in TCA-induced toxicity in rats benefited hepatic antioxidant status and improved liver injury and damage in male albino rats exposed to TCA.

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