Protective effects of Citrus limonia oil against cisplatin-induced nephrotoxicity

Abstract

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 from Citrus limonia demonstrated significant anti-inflammatory and antioxidant effects. The aim of the current work was to evaluate the protective effects of Citrus limonia oil 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 plus Citrus limonia oil at 100 or 200 mg/kg for 10 days, respectively. GC-MS analysis showed that the major components in Citrus limonia oil were D-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 of Citrus limonia oil attenuated these effects in renal histopathological, morphometric, and ultrastructural examinations, frequently in a dose-dependent manner. In conclusion, Citrus limonia oil can ameliorate the toxic effect of cisplatin on mice kidneys, probably through its antioxidant and anti-inflammatory effects.

Rosmarinic acid relieves cisplatin‐induced ovary toxicity in female mice via suppression of oxidative stress and inflammation

“…However, CIS administration has been accompanied by nephrotoxicity, cardiotoxicity, hepatotoxicity, and ovarian toxicity. [13][14][15][16][17][18] Previous research suggests that CIS induces cytotoxicity in healthy tissue via continuous generation of reactive oxygen species (ROS), suppressing endogenous antioxidant enzymes, releasing free radicals, and inducing mitochondrial oxidative stress. [19,20] The continued generation of free radicals in the cells is responsible for inducing the pathogenic phase.…”

Dabigatran mitigates cisplatin-mediated nephrotoxicity through down regulation of thrombin pathway

“…Different hypotheses have been investigated and several studies performed to elucidate the etiology of CDDP nephrotoxicity [4] . It has been reported that CDDP can cause glutathione depletion, reactive oxygen species (ROS) production and an increase of inflammatory mediators and apoptotic markers resulting in cell injury and death [5] , [6] . However, this serious problem continues, and many patients are unable to continue treatment with CDDP for a sufficient period of time.…”

Protective Effect of Lemon Essential Oil and Its Major Active Component, D-Limonene, on Intestinal Injury and Inflammation of E. coli-Challenged Mice

“…It was found that the mixture of LEO and a ginger extract substantially decreased the lipid peroxidation intensity in the liver and the brains of mice and increased the resistance of liver and brain lipids to oxidation and the activity of antioxidant enzymes in the liver ( 17 ). Abdel-Daim et al ( 18 ) found that treatment with limonia oil at 100 and 200 mg/kg BW improved all the biochemical alterations in a dose-dependent manner, which could increase the concentration of SOD, and decrease the concentration of MDA. CampêLo et al ( 19 ) found that LEO reduced the level of lipid peroxidation and increased the level of GSH and SOD, catalase and glutathione peroxidase in mouse hippocampus.…”