Paracetamol-induced Liver Damage In Mice Research Articles

In vitro Antioxidant and in vivo Hepatoprotective Activities of Root Bark Extract and Solvent Fractions of Croton macrostachyus Hochst. Ex Del. (Euphorbiaceae) on Paracetamol-Induced Liver Damage in Mice.

BackgroundLiver disease is a major public health threat, particularly in developing countries. Several medicinal plants and formulations have been claimed to have liver protective activities. The present study aimed to evaluate in vitro antioxidant and in vivo hepatoprotective activities of root bark extracts of Croton macrostachyus (Euphorbiaceae).MethodsFree radical scavenging activity of crude extract and solvent fractions of the plant was conducted using the DPPH assay method. Hepatoprotective activities of the crude extract and solvent fractions of the plant were carried out based on paracetamol-induced liver damage in mice. Serum biomarkers (AST, ALT, ALP, total bilirubin and total protein) were assessed to find out the effect. Histopathological examination was also carried out for all groups of mice to further confirm the findings.ResultsAntioxidant assay revealed that the crude extract, aqueous fraction and chloroform fraction of Croton macrostachyus exhibited free radical scavenging activity with IC50 values of 128.6, 168.9, and 406 µg/mL, respectively. Pretreatment of the mice with the crude extract and solvent fractions of Croton macrostachyus significantly reduced ALP (p<0.001), ALT (p<0.001), and AST (p<0.001) levels at all the administered doses compared to the toxic group. The crude extract and chloroform fraction decreased total bilirubin level at doses of 200 mg/kg (P<0.05) and 400 mg/kg (P<0.001). Pretreatment of the mice with 400 mg/kg of the crude extract and aqueous fraction elevated total protein value compared to the paracetamol treated group (P<0.05). The hepatoprotective activities of the plant extracts were confirmed by histopathological studies.ConclusionFrom this study, it can be concluded that the crude extract and solvent fractions of Croton macrostachyus demonstrated antioxidant and hepatoprotective activities.

Hepatoprotective Effects of Various Solvent Extracted Samples of Paeonia Emodi (wall) in Mice with Paracetamol-Induced Hepatotoxicity

The goal of present study is to evaluate and recognize the most effective hepatoprotective solvent fractions of methanolic extract of Paeonia emodi by fractionating and assessing its fractions for hepatoprotective effect in paracetamol-induced liver damage in mice. In this study, some liver-related serum parameters such as AST, ALP, and ALT were studied. Maximum reduction was caused by aqueous extract (61.08 %) followed by a butanol extract (60.26 %), chloroform extract (48.76 %), crude extract (45.48 %) and drug (37.93 %), in case of ALT. During the study of AST, chloroform extract caused a maximum reduction (65.94 %), followed by a butanol extract (60.43 %), aqueous extract (57.13 %), crude extract (57.13 %) and drug (43.94 %). During the study of ALP aqueous fraction caused a maximum reduction (47.22 %), followed by a butanol fraction (44.44 %), chloroform (41.51 %), methanol extract (34.72 %) and drug (20.83 %). In all the treatment groups the serum levels of ALT, AST and ALP were significantly lower as compared to those of untreated controlled group (P&lt;0.05). The present research showed that Paeonia emodi has the potential to reduce paracetamol-induced hepatotoxicity in mice and restore the normal liver function.

Polyphenolic profiles and the in vivo antioxidant effect of nipa vinegar on paracetamol induced liver damage

Nipa vinegar, which is rich in gallic acid and protocatechuic acid, has reverted the paracetamol-induced liver damage in mice by reduction of inflammation and oxidative stress.

Antioxidant effects of pineapple vinegar in reversing of paracetamol-induced liver damage in mice.

BackgroundPineapple (Ananas comosus) was demonstrated to be hepatoprotective. This study aims to investigate the reversing effects of pineapple vinegar on paracetamol-induced liver damage in murine model.MethodsPineapple juice was fermented via anaerobic and aerobic fermentation to produce pineapple vinegar. Male BALB/c mice (n = 70) were separated into 7 treatment groups (n = 10). Pineapple vinegar (0.08 and 2 mL/kg BW) and synthetic vinegar were used to treat paracetamol-induced liver damage in mice. The hepatoprotective effects were determined by serum biochemistry profiles (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and triglyceride (TG)), liver antioxidant levels (ferric-reducing ability plasma (FRAP), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione assays (GSH)) and histopathological examination with hematoxylin and eosin (H&E) staining. The effects were further evaluated by the expression levels of iNOS, NF-κB, and cytochrome P450 2E1 by quantitative real-time PCR and Western blot analyses. Vinegar samples were also tested for in vitro antioxidant (FRAP, 2,2-diphenyl-2-picrylhydrazyl (DPPH), and total phenolic content (TPC)). Soluble phenolic acid contents in the samples were identified by HPLC.ResultsPineapple vinegar contained 169.67 ± 0.05 μg GAE/mL of TPC, with 862.61 ± 4.38 μg/mL gallic acid as the main component. Oral administration of pineapple vinegar at 2 mL/kg BW reduced serum enzyme biomarker levels, including AST (P = 0.008), ALT (P = 0.006), ALP (P= 0.002), and TG (P = 0.006) after 7 days of paracetamol treatment. Liver antioxidant levels such as hepatic glutathione (P = 0.003), SOD (P < 0.001), lipid peroxidation (P = 0.002) and FRAP (P <0.001) were restored after the treatment. Pineapple vinegar reduced the expressions of iNOS (P = 0.003) and NF-kB (P = 0.003) and the level of NO (P = 0.003) significantly. Pineapple vinegar also downregulated liver cytochrome P450 protein expression.ConclusionsOral administration of pineapple vinegar at 0.08 and 2 mL/kg BW reduced serum enzyme biomarker levels, restored liver antioxidant levels, reduced inflammatory factor expressions, and down regulated liver cytochrome P450 protein expression in paracetamol-induced liver damage in mice.

Antioxidant and hepatoprotective effects of the food seasoning curry leaves Murraya koenigii (L.) Spreng. (Rutaceae)

The curry leaf water extract, which is rich in gallic acid, reversed paracetamol-induced liver damage in mice by reducing inflammation and oxidative stress.

Prevention of paracetamol-induced liver damage in mice with glutathione

Prevention of paracetamol-induced liver damage in mice with glutathione

Hepatoprotective activity of the total flavonoids from Rosa laevigata Michx fruit in mice treated by paracetamol

In the study, the protective activity of the total flavonoids (TFs) from Rosa laevigate Michx fruit was evaluated in paracetamol-induced liver damage in mice. TFs (50, 200 mg/kg) were administered via gavage daily for 5 days before paracetamol (400 mg/kg, i.v.) treatment. After the experiment, the levels of serum ALT (alanine aminotransferase), AST (aspartate aminotransferase) and MDA (malondialdehyde) were decreased by 78.42%, 70.85% and 30.52%, respectively, while SOD (superoxide dismutase) and GSH (reduced glutathione) were significantly increased compared with model group ( p < 0.05). Further mechanisms study indicated that the TFs could significantly increase the protein expressions of Procaspase-3, Procaspase-8, FasL, Prohibitin and Bcl-2, and markedly decrease the protein expressions of Fas, Bax, p53 and NF-κB p65 compared with the mice treated by paracetamol. Meanwhile, the mRNA level of TNF-α was also down-regulated after the TFs treatment. Our results suggest that the TFs with a striking beneficial activity can be developed to be a potential hepatoprotective drug.

Hepatoprotective and antioxidant effects of gallic acid in paracetamol-induced liver damage in mice

The aim of this research paper was to investigate the hepatoprotective and antioxidant effects of gallic acid in paracetamol-induced liver damage in mice. In the present study, the hepatoprotective and antioxidant effects of gallic acid were evaluated against paracetamol-induced hepatotoxicity in mice and compared with the silymarin, a standard hepatoprotective drug. The mice received a single dose of paracetamol (900 mg/kg body weight i.p.). Gallic acid (100 mg/kg body weight i.p.) and silymarin (25 mg/kg body weight i.p.) were administered 30 min after the injection of paracetamol. After 4 h, liver marker enzymes (aspartate transaminase, alanine transaminase and alkaline phosphatase) and inflammatory mediator tumour necrosis factor-alpha (TNF-alpha) were estimated in serum, while the lipid peroxidation and antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glutathione) were determined in liver homogenate of the control and experimental mice. Increased activities of liver marker enzymes and elevated TNF-alpha and lipid peroxidation levels were observed in mice exposed to paracetamol (P < 0.05), whereas the antioxidant status was found to be depleted (P < 0.05) when compared with the control group. However gallic acid treatment (100 mg/kg body weight i.p.) significantly reverses (P < 0.05) the above changes by its antioxidant action compared to the control group as observed in the paracetamol-challenged mice. The results clearly demonstrate that gallic acid possesses promising hepatoprotective effects.

Water-extractable phytochemicals from Phyllanthus niruri exhibit distinct in vitro antioxidant and in vivo hepatoprotective activity against paracetamol-induced liver damage in mice

The antioxidative and hepatoprotective potential of Phyllanthus niruri, a widely used medicinal plant in Brazil, were investigated. The aqueous extracts of leaves showed inhibition against thiobarbituric acid-reactive species (TBARS), induced by different pro-oxidants (10 μM FeSO 4 and 5 μM sodium nitroprusside) in rat liver, brain and kidney homogenates. The extracts also lowered the formation of TBARS in phospholipids extracted from egg yolk. The plant exhibited strong antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl free radical (IC 50, 43.4 ± 1.45 μg/ml) and iron chelation assay. The hepatoprotective activity of the extracts were also demonstrated in vivo against paracetamol-induced liver damage, as evidenced by the decrease in serum glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT), and increased catalase activity in the liver in treatment groups, compared to the control. The results of the present study suggest the potential use of P. niruri in the treatment of various diseases, among which liver disease is the most important, due to its ability to act as an antioxidant. Furthermore, since the treatment of human intoxications with paracetamol is always limited to the administration of N-acetyl-cysteine, additional studies would be important to determine whether aqueous extracts of P. niruri could increase the efficacy of N-acetyl-cysteine against paracetamol acute hepatotoxicity.

EC-SOD gene therapy reduces paracetamol-induced liver damage in mice.

Paracetamol overdose causes acute liver damage which leads to severe centrilobular hepatic necrosis. The hepatotoxic effect is caused by reactive metabolites and oxidative stress. Since extracellular superoxide dismutase (EC-SOD) protects tissues against the harmful effects of superoxide anion, the hypothesis that systemic adenovirus-mediated EC-SOD gene transfer could reduce liver damage was tested. Mice were given paracetamol (600 mg/kg) enterally 2 days after adenovirus-mediated gene transfer of EC-SOD (2 x 10(9) pfu). Five days after gene transfer, plasma and tissue samples were collected for clinical chemistry analyses and tissue pathology evaluation. EC-SOD was expressed in a dose-dependent manner with the highest enzyme activity occurring 3 days after the gene transfer. Clinical chemistry and tissue pathology analyses showed that adenoviral EC-SOD gene transfer significantly attenuated release of liver enzymes and inhibited necrosis and apoptosis caused by paracetamol overdose. The results indicate the involvement of superoxide anion in paracetamol-mediated liver damage and suggest a possible protective role for EC-SOD gene transfer in paracetamol-induced liver damage.