Hepatoprotective and antioxidant activity of Phaseolus trilobus, Ait on bile duct ligation induced liver fibrosis in rats

Fursule, Ravindra A.; Patil, Savita D.

doi:10.1016/j.jep.2010.04.021

Cited by 21 publications

(17 citation statements)

References 8 publications

(6 reference statements)

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“…[21][22][23] These results suggest that gomisin A enhances the antioxidant defense system, inhibits lipid peroxidation, and thus has the potential to prevent CCl 4 -induced liver damage.…”

Section: Discussionmentioning

confidence: 77%

The Molecular Mechanisms of the Hepatoprotective Effect of Gomisin A against Oxidative Stress and Inflammatory Response in Rats with Carbon Tetrachloride-Induced Acute Liver Injury

Teraoka

Shimada

Aburada

2012

Biological & Pharmaceutical Bulletin

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Oxidative damage and inflammation are implicated in the pathogenesis of liver injury and fibrosis. In the present study, we investigated the molecular mechanism by which gomisin A conferred a hepatoprotective effect, focusing on its antioxidant and anti-inflammatory effects using rats with carbon tetrachloride (CCl 4 )-induced acute liver injury. Pretreatment with gomisin A prior to the administration of CCl 4 markedly prevented an increase in alanine aminotransferase, aspartate aminotransferase, and histological hepatic lesions. Gomisin A was also associated with a decrease in hepatic lipid peroxidation, and increased superoxide dismutase activity, suggesting that gomisin A has an antioxidant effect. In addition gomisin A treatment ameliorated mRNA levels of CCl 4 -induced inflammatory mediators, including tumor necrosis factor-α, interleukin-1β and inducible nitric oxide (NO) synthase, and the protein levels of transcriptional upregulator nuclear factor kappa B (NF-κB) and phospho-inhibitor of NF-κB (IκB). Furthermore, α-smooth muscle actin (α-SMA), a myofibroblast marker, was also inhibited by gomisin A treatment. These results suggest that gomisin A inhibits the oxidative stress and activation of NF-κB, leading to down-regulation of pro-inflammatory mediators and amelioration of fibrogenesis.Key words gomisin A; oxidative stress; inflammatory response; carbon tetrachloride; acute liver injuryThe liver has the important function of metabolizing and eliminating biological and xenobiotic compounds. Liver injury is considered to be a serious health problem leading to acute hepatitis, cholestasis, and cirrhosis. Hepatocellular injury usually leads to oxidative stress, inflammation, and activation of the innate immune system. These factors lead to the release of pro-inflammatory cytokines (that can result in hepatic necrosis) and of pro-fibrogenic cytokines that may cause increased synthesis of extracellular matrix components by activation of quiescent hepatic stellate cells (HSCs).

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“…[21][22][23] These results suggest that gomisin A enhances the antioxidant defense system, inhibits lipid peroxidation, and thus has the potential to prevent CCl 4 -induced liver damage.…”

Section: Discussionmentioning

confidence: 77%

The Molecular Mechanisms of the Hepatoprotective Effect of Gomisin A against Oxidative Stress and Inflammatory Response in Rats with Carbon Tetrachloride-Induced Acute Liver Injury

Teraoka

Shimada

Aburada

2012

Biological & Pharmaceutical Bulletin

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“…Liver specimens (10%) in 0.15 M KCl was prepared in an homogenizer (Fursule and Patil, 2010) from Xinzhi Biotechnology Corporation (Ningbo, China) and centrifuged at 3000 rpm for 10 min at 4 • C according to the instructions of the kits provided by Jiancheng Institute of Biotechnology (Nanjing, China) by Remi cool centrifuge and the supernatants were used immediately for liver MPO, LPO, GSH, SOD, CAT, GPx and GST assays. Protein concentrations were determined according to the method of Bradford (Bradford, 1976), using bovine serum albumin as standard.…”

Section: Assays Of the Enzymes And Components In Liver Specimensmentioning

confidence: 99%

Protective effect of Danning tablet on acute livery injury with cholestasis induced by α-naphthylisothiocyanate in rats

Ding

Zhang

Dou

et al. 2012

Journal of Ethnopharmacology

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“…Our results are consistent with those reported in previous studies. Ji et al, and Fursule et al, reported that while BDL increased the levels of GPT, GOT, and ALP and the level of T-bil in the serum of BDL rats, no significant difference was observed in the body weights between the control and BDL rats throughout the experimental period [27,28]. These observations suggested the usefulness of BDL for inducing bile duct stricture in rats to investigate the effects of BDL on the PK of TAC.…”

Section: Discussionmentioning

confidence: 96%

Effects of bile duct stricture on the pharmacokinetics of the immunosuppressant tacrolimus in rats

Kobuchi¹,

Fukushima²,

Maeda³

et al. 2013

Interact Med Chem

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Background: To investigate the effects of bile duct stricture on the pharmacokinetics of the immunosuppressant tacrolimus, the pharmacokinetics of tacrolimus in rats with bile duct ligation were evaluated and the effects of the amount of intestinal bile on intestinal tacrolimus absorption were determined. Methods:In vivo pharmacokinetic studies and in vitro metabolic studies in rats with bile duct ligation were performed. In addition, an in situ absorption study was performed. Results: After an intravenous bolus injection of tacrolimus, the area under the blood concentration-time curve in rats with bile duct ligation was approximately 1.9-fold greater than that in control rats. The total clearance and steady-state volume of distribution decreased in the rats with bile duct ligation by 44.1% and 40.4%, respectively. Moreover, the production ratios of demethyl-tacrolimus and hydroxy-tacrolimus in the hepatic microsomes of rats with bile duct ligation were 59-62% and 21-43%, respectively, lower than the corresponding ratios in control rats. The area under the blood concentration-time curve after intraloop administration of tacrolimus with double-diluted bile or with saline was significantly lesser than that with undiluted bile. Significant positive linear correlations were observed between the amount of intestinal bile and the area under the blood concentration-time curve of tacrolimus (r=0.999, p<0.05). Conclusions:The decrease in the hepatic intrinsic clearance of tacrolimus in rats with bile duct ligation suggests that the bile duct stricture might contribute to the clinically observed inter-and intra-patient pharmacokinetic variability. The amount of bile in the intestine is an important factor that should be considered during tacrolimus treatment. When the route of administration of tacrolimus is changed from injection to an oral one or during long-term oral administration of tacrolimus in patients with bile duct stricture, the decrease in absorption should be taken into account, and the dose should be adjusted accordingly. Taken together, the data indicate that personalized therapy is required for patients with bile duct stricture, and it is necessary to carefully evaluate therapeutic drug monitoring data for tacrolimus.

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Hepatoprotective and antioxidant activity of Phaseolus trilobus, Ait on bile duct ligation induced liver fibrosis in rats

Cited by 21 publications

References 8 publications

The Molecular Mechanisms of the Hepatoprotective Effect of Gomisin A against Oxidative Stress and Inflammatory Response in Rats with Carbon Tetrachloride-Induced Acute Liver Injury

The Molecular Mechanisms of the Hepatoprotective Effect of Gomisin A against Oxidative Stress and Inflammatory Response in Rats with Carbon Tetrachloride-Induced Acute Liver Injury

Protective effect of Danning tablet on acute livery injury with cholestasis induced by α-naphthylisothiocyanate in rats

Effects of bile duct stricture on the pharmacokinetics of the immunosuppressant tacrolimus in rats

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