PROTECTIVE EFFECT OF ALLOPURINOL ON PARACETAMOL-INDUCED LIVER INJURY IN RATS

Background Liver injury is a major health problem that challenges not only healthcare professionals but also the pharmaceutical industry and drug regulatory agencies. Continuous exposure to certain chemotherapeutic agents, drugs, environmental toxins, viral infections and bacterial invasion within the body can trigger liver injury and eventually lead to various liver diseases.
            Aim: The present investigation aims to elucidate the possible hepatoprotective effect of allopurinol on liver injury induced by administration of a single dose of paracetamol (PCM) to adult male albino rats.
            Methodology: Animals were divided into 4 groups, each of 6 rats. The first group was kept as normal control group received (carboxy methyl cellulose 1 % + tween 80 p.o.). The second group (hepatotoxicity control group) received (750 mg/kg PCM p.o. as a single dose at day 14). The third group received (NAC; 300 mg/kg/day p.o.) on a daily basis for 14 consecutive days. The fourth group (treatment group) received allopurinol (50 mg/kg/day p.o.) also for 14 consecutive days. Method of induction of liver injury by PCM: After 13 days of pre-treatment, animals were fasted for 18 hours then administered the last protected dose at day 14. After 2 hours, PCM was administered then animals were further fasted for 24 hours. After that, animals were sacrificed and blood tissue samples were collected.
            Results: Administration of PCM caused liver injury in rats evidenced by significant increase in serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) content, myeloperoxidase (MPO) activity, total nitrate/nitrite (NOx) production. In addition, significant decreases in hepatic catalase (CAT) activity and hepatic glutathione (GSH) content. Treatment with N-acetyl cysteine (NAC) or allopurinol protect against liver injury as evidenced by significant decreases in hepatic MPO activity, NOx production and MDA content, In addition, significant increases in hepatic CAT activity and GSH content.
            Conclusion: It seems that allopurinol might be protective against liver injury in rats and is promising for further clinical trials.