Therapeutic potential of hemin in acetaminophen nephrotoxicity in rats

Abstract

The therapeutic potential of hemin, the heme oxygenase-1 inducer, was investigated against renal damage induced by acute acetaminophen overdose in rats. Nephrotoxicity was induced by a single oral dose of acetaminophen (2.5 g/kg). Hemin was given as a single s.c. injection (40 μmol/kg), 1 h following acetaminophen administration. Hemin treatment restored blood urea nitrogen and serum creatinine levels that were elevated by acetaminophen. Hemin also compensated deficits in the antioxidant defense mechanisms (reduced glutathione, and catalase and superoxide dismutase activities), and suppressed lipid peroxidation in renal tissue resulted from acetaminophen administration. Hemin attenuated the acetaminophen-induced elevations in renal tumor necrosis factor-α and nitric oxide levels, and caspase-3 activity. Additionally, hemin ameliorated acetaminophen-induced renal damage observed by light microscopic examination. The therapeutic effect afforded by hemin was abolished by prior administration of zinc protoporphyrin-IX, the heme oxygenase-1 inhibitor. It was concluded that hemin represents a potential therapeutic option to protect renal tissue from the detrimental effects of acute acetaminophen overdose. © 2008 Elsevier B.V. All rights reserved.