Curcumin Ameliorates Cisplatin-Induced Nephrotoxicity and Potentiates Its Anticancer Activity in SD Rats: Potential Role of Curcumin in Breast Cancer Chemotherapy

Abstract

Breast malignant neoplastic disease is one of the most complex diseases, as it is a multifactorial disease in which virtually all the targets are instantly or indirectly inter-reliant on each other. Cisplatin (CIS), an inorganic antineoplastic agent is widely utilized in the treatment of various solid tumors including breast cancer. Despite everything, its clinical use is limited, due to ototoxicity, peripheral neuropathy, and nephrotoxicity. The present work was directed to assess the combined result of curcumin (CUR) and CIS in 7, 12-dimethyl benz[a]anthracene (DMBA) induced breast cancer in rats and the prevention of nephrotoxicity induced by the latter. CIS-induced nephrotoxicity was assessed by change in body weight, kidney weight, altered levels of BUN, creatinine, TNF-α, IL-6, IL-8, IL-10, and histopathology of the kidney. Anticancer activity was assessed by measurement of tumor weight, tumor volume, % tumor inhibition, levels of PPAR-γ, and BDNF in mammary tumors and histopathology of mammary tumors. CUR pre-treatment mitigated nephrotoxicity by reducing the inflammatory markers (TNF-α, IL-6, and IL-8; p < 0.001). Further, it reduced mammary cancer via increasing the expression of PPAR-γ (p < 0.001) and decreasing the expression of BDNF (p < 0.001) in mammary tumors. It also reduced tumor volume, further postulating that CUR might adjunct the anticancer activity of the CIS. To the best of our knowledge, this is the first report, which showed that CUR ameliorated CIS-induced nephrotoxicity and improved its anticancer activity in DMBA induced breast cancer in female Sprague-Dawley rats.

The therapeutic effects of curcumin and capsaicin against cyclophosphamide side effects on the uterus in rats

“…Histopathological evaluation of breast tissue showed that cellular degeneration, necrosis, and hemorrhage were severe-very severe in the cisplatin administered group. However, none of these pathological findings occurred in the CRC+ cisplatin group 19 . Our study also showed that oxidant activity (MDA) was high and antioxidant activity (GSH, SOD, GPx, and CAT) was low in the uterus of rats treated with CYC; however in the uterus of the rats in the CRC+CYP group oxidant activity was low and antioxidant activity was high.…”

Efficacy of curcumin on prevention of drug‐induced nephrotoxicity: A review of animal studies

“…Therefore, identifying substances that reverse the pathological changes and recover function is critical. Based on biochemical markers, curcumin is one such substance with the capacity to reverse kidney dysfunction and control nephrotoxicity …”

“…Based on biochemical markers, curcumin is one such substance with the capacity to reverse kidney dysfunction and control nephrotoxicity. 48,51,79…”

Methyl jasmonate enhances the radiation sensitivity of esophageal carcinoma cells by inhibiting the 11-ketoprostaglandin reductase activity of <em>AKR1C3</em>

“…PPARγ pathway activation was found to have a synergistic effect with chemotherapy and radiation therapy. In breast cancer cells, increasing the expression of PPARγ could enhance the cytotoxic effect of cisplatin 38. PPARγ activation could also increase the effects of radiation-induced heart injury 39.…”