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

Parveen Kumar,Rajeev Kumar Sharma,Kunjbihari Sulakhiya,Chandana C Barua

doi:10.3389/fphar.2017.00132

Parveen Kumar, Rajeev Kumar Sharma + Show 2 more

Open Access

https://doi.org/10.3389/fphar.2017.00132

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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.

Highlights

The prevalence of breast carcinoma is increasing by leaps and bounds especially in the developing countries (Kumar et al, 2013b)
Interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α enzyme-linked immunosorbent assay (ELISA) kits were purchased from Invitrogen (Invitrogen Corporation, Frederick, USA)
CIS solution was prepared in normal saline and CUR was suspended in carboxymethyl cellulose (CMC)

Summary

Introduction

The prevalence of breast carcinoma is increasing by leaps and bounds especially in the developing countries (Kumar et al, 2013b). It is the most prevalent form of cancer in developed countries and the second most commonly diagnosed malignancy in the third world countries (Kumar et al, 2015). The inflammation plays a central pathophysiological role in CIS associated nephrotoxicity, as CIS injection induces a cascade of inflammatory responses in the kidney through the release of several cytokines (TNF-α, IL1β etc.) and chemokines [MCP-1, macrophage inflammatory protein (MIP)-2 etc.]. Umpteen theories have been proposed for prevention of its nephrotoxicity but of little/no avail (Ueki et al, 2013)

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