Abstract

Caffeine, a known CNS stimulant is given as an adjunct component in most abused drugs which could be fatal with repeated administration in many circumstances. This paper presents a study to investigate the effect of repeated administration of caffeine at high dose on rat liver, and discusses ethical and policy issues of caffeine use. Long Evans rats were treated with pure caffeine solution in distilled water through intragastric route once daily for consecutive 56 days. Three groups of rats recognized as low dose, high dose and control group received 6mg caffeine / kg BW, 12mg caffeine / kg BW and distilled water, respectively. Rat plasma was examined for liver transaminases and alkaline phosphatases concentrations which were significantly increased in plasma as compared to the control. Both rat plasma and liver homogenate were subjected to estimate malondialdehyde, advanced oxidation protein product, nitric oxide, antioxidant enzyme catalase, glutathione and superoxide dismutase activity. MDA, AOPP, NO levels increased and SOD activity decreased significantly in both plasma and liver as compared to those of control where as CAT and GSH activity remain unchanged. Rat liver tissues were studied histochemically with Hematoxylin and Eosin, and Picro Sirius Red staining. Significantly increased infiltration of inflammatory cells and progressive deposition of collagen fibre were visible in liver tissue of caffeine treated both dose groups as compared to the control. Long term administration of caffeine at higher dose, significantly contributes to liver inflammation and consequent fibrogenesis. This raises significant ethical and policy issues.