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Investigation of the Lipoxygenase Pathway in Cisplatine Induced Nephrotoxicity

Nephrotoxicity is a major side effect for the widely used antineoplastic agent, cisplatin. Several studies have investigated the possible mechanisms for such toxicity. HETEs and leukotrienes were found in several studies to mediate many physiological functions in the kidney including regulation of glomerular filtration or renal vasoconstriction. This study was designed, therefore, mainly to investigate the possible involvement of lipoxygenase (LOX) pathway in cisplatin induced‐nephrotoxicity in Wistar rats. Nephrotoxicity was induced by IP injection of cisplatin (6 mg/kg/day). Genes and protein expression of the major lipoxygenases pathway biomarkers including 5‐LOX, 12‐LOX and 15‐LOX in animals’ kidneys were quantified using real time PCR and western plot, respectively. Cisplatin challenge to the animals markedly altered renal LOX pathway genes expression. There was a marked up regulation in 5‐LOX, 12‐LOX and 15‐LOX genes in the kidneys of cisplatin treated animals. Moreover, protein expressions of 5‐LOX, 12‐LOX, 15‐LOX were also significantly increased in the kidneys of cisplatin treated animals. To the best of our knowledge, the linkage between LOX pathway and cisplatine nephrotoxicity has not been investigated. Combination of several agents with the anticancer drug is frequently used to alleviate the associated side effect. Therefore, the current project is a preclinical study that might provide a therapeutic benefit LOX inhibitors combination with cispaltin.