Pioglitazone, quercetin and hydroxy citric acid effect on cytochrome P450 2E1 (CYP2E1) enzyme levels in experimentally induced non alcoholic steatohepatitis (NASH)

Eur Rev Med Pharmacol Sci. 2014;18(18):2736-41.

Abstract

Objective: Non-Alcoholic Steatohepatitis (NASH) is a severe form of Non Alcoholic Fatty Liver Disease (NAFLD) spectrum, which progresses to the end stage liver disease. A common denominator in the pathogenesis of insulin resistance and nonalcoholic steatohepatitis is increased oxidative stress. Hepatic induction of the pro-oxidant enzyme Cytochrome P450 2E1 (CYP2E1) occurs in both NAFLD and type-2 diabetes. In this study, the comparative effect of pioglitazone, quercetin and hydroxy citric acid on liver CYP2E1 enzyme levels in experimentally induced NASH has been studied.

Materials and methods: The experimental protocol consists of 5 groups viz. Control (n = 6); NASH Induced (n=6); NASH + Pioglitazone (n=6); NASH + Quercetin (n=6); NASH + Hydroxy Citric Acid (n=6). CYP2E1 enzyme levels were detected in liver by immunoblot analysis in all the groups.

Results: CYP2E1 catalytic activity was increased in experimentally induced NASH group compared to control group as evidenced by the Immunoblot analysis. It revealed low CYP2E1 in the experimentally induced NASH, treated with pioglitazone, quercetin and hydroxy citric acid. Mild decrease in the levels of CYP2E1 level was observed in experimental NASH treated with pioglitazone compared to NASH group. Treatment with hydroxy citric acid also showed mild decrease in the levels of CYP2E1. On contrary to the action of pioglitazone and hydroxy citric acid, quercetin showed an approximate 2-fold decrease in the level of CYP2E1 in experimental NASH treated with quercetin compared to NASH group.

Conclusions: Being a powerful antioxidant, quercetin offers absolute protection to liver against NASH by reducing the levels of CYP2E1 and, thereby, reducing CYP2E1 mediated oxidative stress, which is believed to be the one of the key factor in the pathogenesis of NASH. On the other hand, pioglitazone and hydroxy citric acid exerted limited effect on the levels of CYP2E1. This study showed the therapeutic value of quercetin, pioglitazone and hydroxy citric acid in treating NASH.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Citric Acid / pharmacology*
  • Citric Acid / therapeutic use
  • Cytochrome P-450 CYP2E1 / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Male
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / enzymology*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Pioglitazone
  • Quercetin / pharmacology*
  • Quercetin / therapeutic use
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use*
  • Treatment Outcome

Substances

  • Antioxidants
  • Enzyme Inhibitors
  • Reactive Oxygen Species
  • Thiazolidinediones
  • Citric Acid
  • Quercetin
  • Cytochrome P-450 CYP2E1
  • Pioglitazone