Biochemical and Histological Study of Rat Liver and Kidney Injury Induced by Cisplatin

Abstract

Cisplatin is a chemotherapeutic agent widely used in treatment of several cancers. It is documented as a major cause of clinical nephrotoxicity and hepatotoxicity. The purpose of this study was to investigate the involvement of oxidative stress in the pathogenesis of cisplatin-induced liver and kidney injury. Wistar rats were divided into four groups. Group 1 (control) was intraperitoneally (IP) injected with a single dose of 0.85% normal saline. Groups 2, 3 and 4 were IP injected with single doses of cisplatin at 10, 25 and 50 mg/kg body weight (BW), respectively. At 24, 48, 72, 96 and 120 h after injection, BW, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and activity of superoxide dismutase (SOD) and histology of the liver and kidney were evaluated. Cisplatin caused a reduction in BW of rats in groups 2, 3 and 4 at all post injection intervals. The levels of serum ALT, AST, BUN and creatinine and MDA of the kidney and liver were markedly increased especially at 48 and 72 h, whereas the activity of SOD was decreased after cisplatin injection. Liver sections revealed moderate to severe congestion with dilation of the hepatic artery, portal vein and bile duct and disorganization of hepatic cords at 50 mg/kg of cisplatin. Kidney sections illustrated mild to moderate tubular necrosis at 25 and 50 mg/kg of cisplatin. Therefore, oxidative stress was implicated in the pathogenesis of liver and kidney injury causing biochemical and histological alterations.

Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat

“…Nephrotoxicity occurs with high prevalence in the initial days of cisplatin chemotherapy. 9,21 The underlying mechanism of cisplatin-induced nephrotoxicity is still not well known but many recent studies indicate that oxidative stress play an effective role in pathogenesis of kidney injury induced by cisplatin through increasing reactive oxygen species (ROS). 6,22,23 Therefore, antioxidants and free radical scavengers may influence the progression of renal oxidative damage and provide nephroprotection against irreversible cell damage induced by cisplatin.…”

“…These results are consistent with the previous studies on cisplatin-induced nephrotoxicity in experimental animals. 9,23,25 The reduction in body weight following cisplatin treatment in group II, III, and IV may possibly be due to cytotoxic effects on the gastrointestinal tract and by reduced ingestion of food. 33 In this study, cisplatin increased MDA (a secondary product of lipid peroxidation) and decreased thiol content in the kidney homogenates.…”

“…6 Many studies confirm oxidative stress as an important factor in tissues damage and antioxidant agents have been expected to either ameliorate or prevent the nephrotoxicity of cisplatin. [7][8][9] Pomegranate (Punnica granatum L.) from Punicaceae family is native to the region from northern India to Iran. It is also widely cultivated in parts of Southwest America, California, Arizona, and Africa.…”

Amelioration of Cisplatin-Induced Nephrotoxicity in Rats by Curcumin and α-Tocopherol

“…Unfortunately, it exerts various side effects in several organs particularly in the kidney [2]. Only days after initiating treatment, approximately one-third of cisplatin-treated patients exhibit reduced glomerular filtration rate and increased blood urea nitrogen (BUN) and creatinine levels [3].…”

“…NADPH oxidase is an enzyme which catalyzes the generation of O 2 •-in large amounts. O 2 •-is able to rapidly change into other ROS such as hydrogen peroxide (H 2 O 2 ) and • OH [6].…”