Protective effect of sulforaphane pretreatment against cisplatin-induced liver and mitochondrial oxidant damage in rats

Abstract

In the present work was analyzed whether sulforaphane (SFN) may protect against cisplatin (CIS)-induced hepatic damage, oxidant stress and mitochondrial dysfunction. Four groups of male Wistar rats were studied: control, CIS, CIS+SFN and SFN. SFN was given i.p. (500 μg/kg/d × 3 days) before CIS administration (single i.p. injection, 10mg/kg). Rats were sacrificed 3 days after CIS injection to evaluate hepatic damage (histological analysis, liver/body weight ratio and serum activity of aspartate aminotransferase and alanine aminotransferase), oxidant stress (lipid peroxidation and protein carbonyl and glutathione content), antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase and superoxide dismutase) in liver homogenates and isolated mitochondria and mitochondrial function (oxygen consumption using either malate/glutamate or succinate as substrates and the activity of mitochondrial complex I, II, II-III, IV and V). Furthermore it was evaluated if SFN is able to scavenge some reactive oxygen species in vitro. It was found that SFN prevents CIS-induced (a) hepatic damage, (b) oxidant stress and decreased activity of antioxidant enzymes in liver and mitochondria and (c) mitochondrial alterations in oxygen consumption and decreased activity of mitochondrial complex I. It was also found that the scavenging ability of SFN for peroxynitrite anion, superoxide anion, singlet oxygen, peroxyl radicals, hydrogen peroxide and hydroxyl radicals was very low or negligible. The hepatoprotective effect of SFN was associated to the preservation of mitochondrial function, antioxidant enzymes and prevention of liver and mitochondrial oxidant stress.