Abstract

Background: Paracetamol, is the most widely used over-the-counter analgesic and antipyretic medication in the world, which has minimal adverse effects at therapeutic dosages. But in high doses causes hepatic damage and oxidative stress. Objectives: The current study was designed to investigate paracetamol toxic effects upon the liver and oxidative stress after repeated oral dose and evaluate possible protective effect of alpha lipoic acid when co-administered with and after paracetamol. Methods: forty eight white albino rats were divided equally into four groups. Each group was subdivided into two sub groups A & B. Group I received gum acacia suspension. Group II received Alpha lipoic acid (50mg/kg) orally. Group III received paracetamol (1 gm/ kg orally) for 4 weeks. Group IV received paracetamol and alpha lipoic acid at the same doses. Sub groups A were euthanized after 4 weeks, while sub groups B were euthanized after 8 weeks. Blood was collected for evaluation of liver functions and oxidative stress marker. The livers were preserved for histopathological examinations. Results: The study proved that repeated administration of paracetamol induced disturbed liver functions and oxidative stress. But this toxic effects decline markedly when alpha lipoic acid (ALA) was coadministered with paracetamol. And more improvement occurs when ALA was administered for another 4 weeks after stoppage of paracetamol. Conclusions: The present study concluded that repeated paracetamol administration has hepatotoxic and oxidative stress effect and alpha lipoic acid has a protective effect against such harmful effects especially when ALA was administered for another 4 weeks after stoppage of paracetamol.

Highlights

  • Paracetamol is used as analgesic and antipyretic drug in a wide manner; it is safe if used at the recommended dosage (Kanno et al, 2006)

  • Paracetamol oxidation occurs by a CYP 450 oxidase enzyme to form N-acetyl-p-benzoquinone imine (NAPQI), which is rapidly conjugated with glutathione intracellular to form 3-glutathione-S-ylparacetamol it is eliminated in urine or bile with lesser extent (Gelotte et al, 2007)

  • The present study aims to evaluate the protective effects of alpha lipoic acid (ALA) on liver toxicity and the oxidative stress induced by paracetamol

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Summary

Introduction

Paracetamol is used as analgesic and antipyretic drug in a wide manner; it is safe if used at the recommended dosage (Kanno et al, 2006). Objectives: The current study was designed to investigate paracetamol toxic effects upon the liver and oxidative stress after repeated oral dose and evaluate possible protective effect of alpha lipoic acid when co-administered with and after paracetamol. Group IV received paracetamol and alpha lipoic acid at the same doses. Results: The study proved that repeated administration of paracetamol induced disturbed liver functions and oxidative stress. This toxic effects decline markedly when alpha lipoic acid (ALA) was coadministered with paracetamol. Conclusions: The present study concluded that repeated paracetamol administration has hepatotoxic and oxidative stress effect and alpha lipoic acid has a protective effect against such harmful effects especially when ALA was administered for another 4 weeks after stoppage of paracetamol

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