Isoniazid- and rifampicin-induced oxidative hepatic injury - Protection by N-acetylcysteine

S. Attri, S. V. Rana, K. Vaiphei, C. P. Sodhi, R. Katyal, R. C. Goel, C. K. Nain, K. Singh

Research output: Contribution to journalArticlepeer-review

Abstract

The role of N-acetylcysteine (NAC), a glutathione (GSH) precursor, was investigated in protection against isoniazid- (INH) and rifampicin- (RIF) induced oxidative hepatic injury in young Wistar rats. The hepatotoxic dose of INH and RIF was 50 mg kg-1 day-1 each and the hepatoprotective dose of NAC was 100 mg kg-1 day-1. All drugs were administered intraperitoneally (i.p.) in sterile water (4.0 ml kg-1 day-1) over a period of 3 weeks. Status of oxidative/antioxidative profiles was the mechanistic approach to assess the hepatotoxicity and/or hepatoprotection. The oxidative injury in INH-RIF co-exposed animals was closely associated with significant decline of GSH and related thiols, as well as with compromised antioxidant enzyme system. The oxidative stress was further supported by increased lipid peroxidation observed in these animals. The co-administration of NAC prevented the induction of oxidative stress in INH-RIF co-exposed animals. The amelioration of oxidative stress by NAC was faithfully reflected as normal morphology in these animals, except the presence of mild degree of portal triaditis in one animal co-exposed to INH-RIF and NAC. In contrast, the animals co-exposed to INH-RIF alone showed histological lesions which ranged from intralobular inflammation to patchy necrosis. These results suggest that INH-RIF-induced oxidative injury can be prevented by supporting the cellular antioxidant defense mechanism by NAC.

Original languageEnglish (US)
Pages (from-to)517-522
Number of pages6
JournalHuman and Experimental Toxicology
Volume19
Issue number9
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Hepatoprotection
  • Isoniazid
  • N-acetylcysteine
  • Oxidative stress
  • Rifampicin

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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