The role of oxygen free radicals in cisplatin-induced acute renal failure in rats

Abstract

We examined the role of oxygen free radicals in cisplatin-induced acute renal failure (ARF). The intravenous injection of cisplatin (5 mg/kg body weight) induced an increase in serum creatinine and tubular damage in the outer stripe of the outer medulla in rats. The renal content of malondialdehyde (MDA) transiently increased. Treatment with the free radical scavengers dimethylthiourea (DMTU) or lecithinized superoxide dismutase (L-SOD) attenuated the increase in serum creatinine. The beneficial effect of DMTU, a hydroxyl radical scavenger, was associated with less accumulation of MDA, less tubular damage, and enhanced expression of proliferating cell nuclear antigen (PCNA) in the damaged tubular cells, but not with improvement of reduced renal blood flow (RBF). On the other hand, the beneficial effect of L-SOD, a superoxide anion scavenger, was associated with preservation of RBF and increased urinary guanosine 3',5'-cyclic monophosphate excretion but not with modification of tubular damage or PCNA expression. These results suggest that (1) cisplatin-induced nephrotoxicity was associated with lipid peroxidation, (2) the hydroxyl radical scavenger prevented ARF through both attenuation of tubular damage and enhanced regenerative response of the damaged tubular cells, and (3) the superoxide anion scavenger did the same through preservation of RBF. It follows that oxygen free radicals may play an important role in cisplatin-induced ARF by reducing RBF and inducing tubular damage.

Effects of Grape seed Extract and Origanum Onites Essential Oil on Cisplatin-Induced Hepatotoxicity in Rats

“…29,30 In the present study, an increment in MDA, a highly reactive compound and remarkable marker for oxidative stress and a decrement in GSH-Px and SOD activities, which are key antioxidants, were found in the liver of rats treated with cisplatin. After understanding the possible role of free radicals incispaltin-induced oxidative liver damage, several agents were added to the therapy as an adjuvant supplement and they attempted to protection and/or to prevent the side effects of chemotherapeutics.…”

Protective Effects of Capsaicin against Cisplatin-Induced Nephrotoxicity in Rats

“…This decreased activity may be due to loss of copper and zinc, which are essential for the enzyme activity or reactive oxygen species-induced enzyme inactivation. 27) Recent evidences 2,4,24) have indicated that the free radicals and reactive oxygen species are involved in the CDDP-induced oxidative stress because of depletion of the GSH concentration and decreased antioxidant enzyme activity in the kidneys. These observations also support the hypothesis that part of the mechanism of nephrotoxicity in the CDDP-treated animals is related to depletion of antioxidants.…”

Cisplatin Cytotoxicity of Auditory Cells Requires Secretions of Proinflammatory Cytokines via Activation of ERK and NF-κB

“…A number of studies have demonstrated the direct cytotoxic mechanisms of cisplatin including DNA damage (Leibbrandt et al 1995;Ries et al 1986), mitochondrial dysfunction (Sugiyama et al 1989), formation of reactive oxygen species (ROS) (Matsushima et al 1998), and caspase activation (Kaushal et al 2001). In particular, cisplatin ototoxicity occurs primarily in the cochleae, especially in the outer hair cells (OHCs) of the organ of Corti.…”