Protective effects ofCitrus limoniaoil against cisplatin-induced nephrotoxicity

Cisplatin is broadly used in the treatment of malignancies. However, the high incidence of nephrotoxicity following cisplatin use deters its clinical utility. Former studies have shown that the essential oils, obtained fromCitrus limoniademonstrated significant anti-inflammatory and antioxidant effects. The aim of the current work was to evaluate the protective effects ofCitrus limoniaoil against cisplatin-induced nephrotoxicity. Thirty-two adult male mice were divided into four groups, eight mice each. The control group received distilled water, and the second group received a single intraperitoneal injection of cisplatin (20 mg/kg), while the third and fourth groups received cisplatin plusCitrus limoniaoil at 100 or 200 mg/kg for 10 days, respectively. GC-MS analysis showed that the major components inCitrus limoniaoil wered-limonene, 5-methyl-pentadecane, (n)-menthol, 3,7-dimethyl-(E)-2,6-octadienal, 3,7-dimethyl-2,6-octadienal, and nonadecane. Biochemical analysis showed that cisplatin intoxication was associated with significantly increased (p < 0.05) serum levels of urea and creatine and pro-inflammatory cytokines, as well as augmented renal tissue oxidative stress. Light microscopic examination showed loss of renal architecture, atrophied glomeruli, interstitial hemorrhage, dilated cortical tubules with cast formation, and excessive collagen production. Electron microscopic examination revealed compressed and karyorrhectic endothelial nuclei with chromatin condensation in the glomeruli, accumulation of mesangial matrix, and obliteration of glomerular blood capillaries. Co-administration ofCitrus limoniaoil attenuated these effects in renal histopathological, morphometric, and ultrastructural examinations, frequently in a dose-dependent manner. In conclusion,Citrus limoniaoil can ameliorate the toxic effect of cisplatin on mice kidneys, probably through its antioxidant and anti-inflammatory effects.