Hepatoprotective Action of Dehydrozingerone in Carbon Tetrachloride and Thioacetamide-induced Hepatotoxicity in Wistar Rats

Study of Silymarin on Ethanol Induced Hepatotoxicity and Expression of Bcl-2, Bax and p53 Levels

Methanolic extract and fractions, ethylacetate (EtF) and butanol (BuF) of leaves of African mistletoe (Tapinanthus bangwensis, Engl. & K. Krause) were evaluated for their hepatoprotective potential using CCl4-induced hepatotoxicity in Wistar albino rats. The activities of the marker enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and bilirubin were highest in rats treated with CCl4 alone. Oral administration at a fixed dose of 400 mg/kg body weight (BW) of the extract and fractions of T. bangwensis for seven days significantly (p ≤ 0.05) decreased the activity of marker enzymes and bilirubin. Total protein concentration increased significantly (p ≤ 0.05). These extracts also decreased the concentration of thiobarbituric acid reactive substances (TBARS) which indicated a reduction in lipid peroxidation. Histopathological examination of hepatocytes of rats administered methanolic extract (MeE) and fractions (EtF and BuF) showed normal architecture whereas rats treated with CCl4 alone was characterized by necrosis of the liver. Generally, among the three extracts, the BuF and EtF showed more hepatoprotective effect. The crude methanolic extract did not show any mortality up to a dose of 2000 g/kg BW. These findings suggest that T. bangwensis possesses strong antioxidant properties and hepatoprotective potentials against CCl4-induced hepatotoxicity in rats.

Hepatoprotective drugs are not available for use in modern medicine and different parts of medicinal plants like Neem (Azadirachta indica) are used as hepatoprotectants in traditional medicine. Although there are scientific reports of its hepatoprotective activity on acute administration, we found only one study which had evaluated its hepatoprotective effect on chronic administration. Objectives: To evaluate the effect of chronic oral administration of Neem on paracetamol-induced hepatotoxicity in Wistar rats. Methods: We randomly assigned 72 male and female Wistar albino rats to four groups of 18 animals each and orally administered Distilled water 5ml/kg body weight/day to Groups A (Normal control) and B (Experimental control), 500 mg/kg aqueous Neem leaf extract (Test) to Group C and Silymarin suspension (Standard) 100mg/kg/day to Group D for 30 days. On the 8th day, we induced hepatotoxicity with Paracetamol 2g/kg body weight single dose to groups B, C and D. We performed liver function tests, recorded liver weights and examined liver histology of six rats from each group on 10th, 20th and 30th days. Results: We observed significant difference (P

BackgroundThe liver is the vital organ which plays a major role in metabolism with numerous functions in the human beings such as protein synthesis, hormone production, and detoxification. Present research work is focused on hepatoprotective potential of chloroform (PNFC) and ethyl acetate (PNFEA) endophytic fractions from Phyllanthus niruri Linn. against CCl4-induced hepatotoxicity in albino Wistar rats. To test our hypothesis, both endophytic fungal fractions were tested for vitro antioxidant and in vivo hepatoprotective activity. Serum biochemical parameters like SGOT, SGOT, SALP, cholesterol, bilirubin, and protein were estimated to assess hepatoprotective activity.ResultsGroup of rats treated with CCl4 possess marked hepatic damage and oxidative stress which indicates that cellular leakage and loss of functional integrity of cell membrane in liver. PNFC and PNFEA fractions of endophyte from Phyllanthus niruri Linn. stem have significantly reduced the elevated levels of biomarkers like SGPT, SGOT, SALP, bilirubin, cholesterol, and total protein in CCl4-induced hepatotoxicity in rats. The results obtained confirm hepatoprotective activity of endophytic fractions (PNFC and PNFEA) mediated through the stabilization of plasma membrane, repair of hepatic tissue damage, return of biochemical marker levels to normal, and regeneration of hepatocytes. Histopathological observations revealed improvement in the liver architecture after the treatment of secondary metabolites of endophytic fractions against CCl4-induced liver damage. Both fungal endophytes PNFC and PNFEA showed DPPH scavenging activity with IC50 of 97.79 μg/ml and 108.40 μg/ml, respectively, and possess antioxidant potential. Presence of flavonoids in the both fractions of endophytes may be a possible reason for its antioxidant potential and identified as Eurotium amstelodami strain.ConclusionBoth fungal endophytes PNFC and PNFEA possess hepatoprotective potential due to the presence of secondary metabolites of fungi, i.e., Eurotiumam stelodami strain which support the claim endophytes and act as a potent biomedicine for treatment of various chronic diseases.

Introduction: Acute acetaminophen poisoning leads to fulminant hepatic failure and renal tubular damage. N-Acetyl Cysteine (NAC), an antidote for acetaminophen poisoning, carries its own adverse effect profile such as anaphylactoid reactions, cerebral oedema and hyponatremia at high doses. Aerva lanata, an erect or prostate herbaceous weed has a wide range of medicinal uses like, hepatoprotection, nephroprotection, antiasthamatic and antiamoebic. Previous study on rats have shown that hydroalcoholic root extract of Aerva lanata has significant hepatoprotective property when administered before acetaminophen. Aim: To evaluate the effect of hydroalcoholic root extract of Aerva lanata and NAC, as monotherapy and in combination, for acetaminophen induced hepatotoxicity in albino Wistar rats. Materials and Methods: This was an experimental animal study. Thirty adult male albino Wistar rats were equally divided into five groups: group I-vehicle, group II-acetaminophen only, group III- acetaminophen+NAC, group IV-acetaminophen+Aerva lanata root extract, group V-Acetaminophen+NAC+Aerva lanata root extract. Hepatotoxicity was induced in rats belonging to groups II, III, IV and V using acetaminophen (2 g/kg p.o). All rats were sacrificed after 72 hours of drug administration, blood samples were sent for biochemical analysis. Liver and kidney samples were sent for histopathological studies. Results were analysed using one-way ANOVA followed by post hoc Dunnett t-test. Results: Root extract of Aerva lanata significantly reduces the liver enzyme markers Aspartate Transaminase (AST), Alanine Transaminase (ALT), Gamma Glutamyl Transferase (GGT) and bilirubin) and blood urea concentration. The combination therapy (root extract with NAC) showed a highly significant decrease in AST, ALT, GGT (p<0.001), bilirubin (p<0.01) and blood urea (p<0.001) when compared with the paracetamol group. A significant reversal of liver injury was seen in histopathological studies. Conclusion: The combination therapy showed better improvement of liver enzyme and renal parameters, along with significant improvement in histopathological changes. Hence, combination of hydroalcoholic root extract of Aerva lanata along with NAC can be effective in treating acetaminophen poisoning.

Capparis sepiaria L. known as Himsra is an important drug in Ayurveda. In this study extracts of the root of C. sepiaria were evaluated for their hepatoprotective potential on acetaminophen-induced hepatotoxicity in albino Wistar rats. The extent of hepatoprotection was evaluated by estimating the serum levels of hepatic transaminases (SGPT and SGOT), alkaline phosphatase (ALP), total protein (TP), and bilirubin (total and direct). Aqueous and ethanol extracts of C. sepiaria significantly reduced the increased liver weight as well as serum levels of SGPT, SGOT, ALP, and bilirubin, and normalized the reduced serum protein levels in the treated rats. These observations were supported by the results of histopathology studies as well. The extracts were also subjected to preliminary organic analysis and chromatographic studies including HPTLC finger print studies. The results indicate that the roots of C. sepiaria show significant hepatoprotective effect on acetaminophen-induced hepatotoxicity, thus substantiating its use as a potential hepatoprotective drug.

Ganoderic acid -loaded solid lipid nanoparticles ameliorate d-galactosamine induced hepatotoxicity in Wistar rats

Hepatoprotective effect of flaxseed and its protein on ethanol-induced hepatotoxicity in adult Wistar rats was investigated. The rats were divided into eight groups of which two served as control (group I: Control for AIN-93M diet groups and group II: Control for cereal-pulse diet groups) and six groups received ethanol orally every day. After 10days along with ethanol, the rats received AIN-93M diet (group III); AIN-93M diet and commercial hepatoprotective formulation (CHF) (group IV); casein replaced by flaxseed protein in AIN-93M diet (group V); cereal-pulse diet (group VI); cereal-pulse diet and CHF (group VII); cereal-pulse diet containing flaxseed (group VIII) for four weeks. The flaxseed and its protein significantly prevented the elevation of plasma markers of hepatic damage, lowered lipid peroxidation, mitigated changes in antioxidant enzymes, and suppressed histopathological signs of hepatic damage. The hepatoprotective effect of flaxseed and its protein was comparable to CHF. These findings implicate the ameliorative effect of flaxseed and its protein on ethanol-induced hepatotoxicity. PRACTICAL APPLICATIONS: Owing to globalization and an increase in earning capacity, alcohol consumption is becoming a part of social life and gradually transforming to addiction. Binge drinking is highly prevalent among low socioeconomic status population, which poses severe risks to health. Alcohol abuse is a public health problem causing three million deaths annually worldwide. Alcohol consumption is known to be a major cause of liver damage worldwide and has contributed to 44% of deaths from liver disease. As abstaining from alcohol is a challenging task, there is an escalating need to formulate potential hepatoprotective agents to prevent alcohol-induced hepatic damage. This study investigates the efficacy of flaxseed and its protein in conferring protection to the liver against ethanol-induced hepatotoxicity. This study also explores the benefits of incorporating flaxseed in the staple cereal-pulse diet. Findings of this study suggest that incorporation of flaxseed or its protein in food formulations can prevent hepatotoxicity and improve the overall quality of life among alcoholics.

Background: Liver disease is considered to be a serious health problem, as the liver is an important organ for the detoxification and deposition of endogenous and exogenous substances. Objective: The present study is carried out to investigate the effect of Vimliv in ethanol-induced hepatotoxicity. Materials and Methods: Ethanol (3 g/kg) was dissolved in water and injected intragastrically, for a period of 35 days. Vimliv was dissolved in carboxy methyl cellulose and administered to rats at doses of 25 and 50 mg/kg for a period of 35 days as coadministration. Results: Administration of Vimliv resulted in significant reduction of blood glucose, serum urea, creatinine, lipid profile and increase in albumin. Administration of Vimliv also shows better pathological effects on liver and kidney. Conclusion: Therefore, this study suggests that Vimliv has the hepatoprotective effect and consequently may alleviate liver and renal damage associated with ethanol-induced hepatotoxicity in rats.

A multi-herbal combination (MHC) of five herbs, namely Punica granatum L., Putranjiva roxburghii Wall., Swertia chirata Buch.-Ham., Tinospora cordifolia (Willd.) Miers and Trigonella corniculata L. was assessed against the paracetamol-induced acute hepatotoxicity in female Wistar rats. The animals were randomly assorted into seven groups with six animals in each group. The rats were pre-treated with MHC (50, 100, and 200 mg/kg bw) and silymarin (50 mg/kg bw) once daily for seven consecutive days via oral route followed by administration of paracetamol (3 g/kg bw) on day 7, an hour after the last administration of MHC and silymarin. It was observed that MHC administration significantly (p ≤ 0.05) overturned the paracetamol-induced increase in serum liver function biomarkers (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and total bilirubin), phase I reaction enzymes (NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase), and oxidant biomarkers (lactate dehydrogenase, lipid peroxidation, lipid hydroperoxides, and protein content). MHC administration also reinstated the paracetamol-induced significant decrease (p ≤ 0.05) in haematological indices (haematocrit, haemoglobin, red and white blood cells, and platelets), phase II reaction enzymes (glutathione-S-transferase and DT-diaphorase), membrane-bound enzymes (Na+/K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase), and antioxidant biomarkers (reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). Overall, MHC at 200 mg/kg bw dose significantly (p ≤ 0.05) sheltered the red blood cells from the assault of free radicals, stabilized the structural and functional integrity of hepatocytes, hindered acetaminophen (APAP) biotransformation to its toxic metabolites, and endorsed conjugating abilities to detoxify toxic entities. Furthermore, MHC significantly (p ≤ 0.05) activated enzymatic machinery to scavenge/inhibit the formation of reactive oxygen species, regulated nucleic acid metabolism, surface potential, and membrane fluidity, attenuated tissue breakdown, quenched peroxyl radicals, and provided protection against tissue injury. The necroinflammatory scores revealed strong evidence of MHC (200 mg/kg bw) effectiveness against the paracetamol-induced hepatotoxicity in rats at p ≤ 0.05. The synergistic effect of major inherent phytoconstituents (kaempferol, ellagic acid, and gallic acid), detected by HPLC-PDA, in MHC might have overturned the paracetamol-induced biochemical toxic alterations in rat liver.

Reports about the impact of Carbon tetrachloride (CCl4) hepatotoxicity on coagulation profile have been inconsistent. Multiple investigators have however demonstrated the effectiveness of silymarin in the resolution of anomalies induced by CCl4, although the effect of silymarin on the impact of CCl4 hepatotoxicity, especially coagulation profile and osmotic fragility have not been investigated. The liver, the primary site for the secretion of coagulation proteins, can become impaired in CCl4 hepatotoxicity, and silymarin reportedly increases hepatic protein synthesis as part of its hepatoprotective mechanism. This study assessed the effect of silymarin on blood coagulation profile and erythrocyte osmotic fragility in CCl4 induced hepatotoxicity in rats. Twenty male Wistar rats were allocated into four groups (n = 5) at random, namely: Control, CCl4 given CCl4 (1 ml/kg) administered intraperitoneally twice a week, Silymarin (S) given silymarin (100 mg/kg/day) orally, and S+CCl4 given silymarin (100 mg/kg/day) orally and (1 ml/kg) CCl4 one hour after, intraperitoneally twice a week for a duration of four weeks. Results showed protraction of activated partial thromboplastin time and thrombin time, increased erythrocyte osmotic fragility, liver damage, dyslipidemia, oxidative stress and lipid peroxidation in rats given CCl4. Silymarin attenuated most of these effects as observed from comparison between CCl4 and S+CCl4 rats. The findings of this study suggests that pretreatment with silymarin attenuated disruption in coagulation profile and erythrocyte osmotic fragility in CCl4 induced hepatotoxicity in Wistar rats.

Mangifera indica (Tommy Atkins) peels, commonly known as mango, is a pharmacologically, ethnomedically, and phytochemically diverse plant. Peels is a major by-product during processing of mango fruit into pulp. In the present study, Thirteen pure bioactive compounds were isolated from methanolic peels extract. Six of them are new ellagitannins,namely,1,2,3,4,6 -Penta-O-galloyl-s-4C1-glupyranose (3); 2,3,6-Tri-O-galloyl-(α/β)-4C1-glucopyranose(4); 2,3-Di-O-galloyl-(α/β)-4C1-glucopyranose,Nilocitin(6);3,6-Di-O-galloyl-(α/β)-4C1-glucopyranose(8);1,6 -Di-O-galloyl- β-4C1-glucopyranose (9) ; 1,3-Di-O-galloyl-β-4C1- glucose (11), which were analyzed for the first time from M. indica (Tommy Atkins) peels. The ameliorative effect of the methanolic extract of M. indica (Tommy Atkins) peels towards the CCl4-induced hepatotoxicity in male Wistar rats through measuring certain biochemical parameters content in the liver were analyzed. The CCl4-treated rats showed a significant decline in the studied the serum levels of high-density lipoprotein (HDL), albumin (A) as well as the hepatic levels of glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD) , glutathione reductase (GR), elevation in the levels of total lipids (TL), triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL), globulin (G), total bilirubin (TBil) , alanine and aspartate aminotransferase and alkaline phosphatase (ALAT and ASAT, ALP) and the hepatic levels of malondialdehyde (MDA). In contrast, the administration of methanol extract, notably improved all the studied parameters. This study showed that CCl4 administration to Wistar rats, at a high dose level, could induce a hepatic injury in addition to certain metabolic alterations. The work was extended to investigate tissue histopathology. Thus, results suggest that the peels extract can be a potential source of an attractive candidate for ameliorating of hepatotoxicity induced by CCl4 through scavenging free radicals, improved liver functions, and normalizing the liver histopathological architecture.

Background: liver is highly susceptible to the toxic and adverse effects of various metabolites and xenobiotics such as alcohol etc. Alcohol abuse leads to hepatotoxicity that is presented in the form of Alcoholic Liver Disease. Aims and Objectives: The present study was conducted to evaluate hepatoprotective activity of polyherbal formulation. The test drug was studied in comparison with marketed formulations in ethanol induced hepatotoxicity in wistar albino rats. Methods: Total 7 groups of animals were studied comparatively to evaluate efficacy of various formulations. Results: It was found that all the formulations tested including all the dosages of Polyherbal Capsule significantly reduced levels of SGOT (Serum glutamic oxaloacetic transaminase), SGPT (Serum glutamate pyruvate transaminase), Alkaline phosphatase (ALP) and Total Bilirubin when compared to ethanol group. There was significant increase in total protein level in Ariliv Tablet, Silymarin and marketed formulation groups. Also, all the formulations tested effectively preserved the structural integrity of the hepatocellular membrane and liver cell architecture damaged by ethanol. When compared between formulation groups there was no statistical significant difference. Conclusion: It can be concluded that Polyherbal Capsule possesses hepatoprotective activity in ethanol induced hepatotoxicity in rats. Polyherbal Capsule can be effectively used in hepatitis caused due to alcohol.

Background: Diazinon is the globally used organophosphorus compound to which humans are exposed through contamination of food and water. Flavonoids in Morus nigra exhibit a wide range of antioxidant, antimicrobial, anti-inflammatory, anti-cancer, anti-radiation properties and have a protective action against oxidative damage and hepatoprotective effects. The study's objective was to evaluate the effects of black mulberry (Morus nigra) extract against diazinon-induced hepatotoxicity in albino Wistar rats. Methodology: A quasi-experimental study was conducted from August 2019 to January 2020 at the Department of Pathology, Isra University, Hyderabad, Pakistan. Under standard colony conditions, thirty-six healthy male albino Wistar rats weighing between 200 and 300 grams were randomly divided equally into three groups: Group-1 (Control), Group-2 (given 60 mg/kg Diazinon daily for 4 weeks), Group-3 (administered Diazinon 60 mg/kg with 500 mg/kg of Morus nigra extract daily for 4 weeks through orogastric intubation). Hepatic tissue of all groups was observed under the light microscope. At the same time, hepatic serum markers were also analyzed. Results: A statistically significant decline in the bodyweight and rise in absolute liver weight of group-3 compared with groups-1 and group-2 (p<0.05). Co-administration of Morus nigra significantly lowered serum AST ad ALT levels. Significant histopathological derangement was observed in group-2 hepatic tissues while group-3 rats hepatic tissues had minimal changes and near-normal hepatic parenchyma. Conclusion: Morus nigra leaf extract has hepatoprotective effects against Diazinon-induced hepatotoxicity in male albino Wistar rats.

The present study was designed to assess the possible hepatoprotective activity of the leaf ethanolic extract of coded plant (Code No. 222**) against carbon tetrachloride (CCl4)-induced hepatic injury in Wistar albino rats. The animals were divided into different groups and treated with 222 leaf ethanolic extract at different concentrations for five days. Silymarin, the known hepatoprotective standard compound (100 mg/kg) was administered for five days. Hepatotoxicity was induced by the subcutaneous administration of a single dose of CCl4: Olive oil (2 mL/kg) on days 2 and 3. The administration of CCl4 resulted in marked increase in serum hepatic enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum bilirubin levels. CCl4 intoxication also resulted in a significant (P=0.05) increase in malondialdehyde (MDA), which is a common marker of lipid peroxidation. The other biochemical parameters such as cholesterol, triglycerides, creatinine, urea and uric acid levels were also increased significantly (P=0.05) compared to normal control group. Changes in serum hepatic enzymes, biochemical parameters and MDA levels induced by CCl4 were reversed by the leaf ethanolic extract of 222 (125 mg/kg) dose. The standard drug silymarin treated group also reversed CCl4-induced changes in biomarkers of liver function and MDA levels. Histopathological studies of the liver samples confirmed the hepatoprotective property of the coded drug 222. It was seen that histopathological damage induced by CCl4 were improved in rat liver, treated with 222 extract. The results of the present study suggested that coded plant (222) leaf ethanolic extract may be used as a hepatoprotective agent against toxic effects caused carbon tetrachloride in the liver.