Concomitant administration of HAART aggravates anti-Koch-induced oxidative hepatorenal damage via dysregulation of glutathione and elevation of uric acid production.

Anti-Koch and HAART have been shown to independently induce toxicity to the liver and kidney, albeit available data are few and inconsistent. The present study evaluates the impact of Anti-Koch and HAART, when administered singly and in combination, on hepatic and renal status, and the possible role of adenine deaminase (ADA)/xanthine oxidase (XO) pathway. Anti-Koch and HAART administration were observed to independently impair hepatic and renal functions, diminish glutathione content, and substantially increase lipid peroxidation (MDA) and nitrogen reactive specie (NO). Coherently, these drugs caused significant accumulation of polymorphonuclear leucocytes, up-regulated ADA/XO signaling, increased uric acid production, and enhanced DNA fragmentation in the liver and kidney. Anti-Koch treatment did not significantly alter hepatic and renal levels of nitric oxide nor induce DNA fragmentation in the kidney. Co-administration of anti-Koch and HAART aggravated the observed biochemical alterations. Findings from the histopathological studies of the liver and renal tissues were in agreement with observed biochemical alterations. In conclusion, this report is the first to reveal that anti-Koch and HAART, when administered singly or in combination, attenuate glutathione content and elevate uric acid production in the liver and kidney via upregulation of ADA/XO signaling with resultant oxidative and nitrosative stress, and increased DNA fragmentation.