Role of renin blocker (Aliskiren) on Cisplatin induced-nephrotoxicity in rats

Abstract

Aliskiren (ALSK), being a direct renin inhibitor, is known for its additional benefit of renoprotection under several pathological conditions. On the other hand, Cisplatin (CP) is one of the most preferred chemotherapeutic agent; however, its clinical utility is limited owing to nephrotoxicity as its primary side effect. This study was aimed to investigate the protective role of ALSK against CP-induced nephrotoxicity in rats. Male Wistar rats were randomly divided into four groups of six animals each. They included vehicle treated normal control, CP (7.5 mg/kg), ALSK (25 mg/kg), and ALSK + CP treated groups. ALSK was orally administered for 2 weeks while CP was administered through the i.p. route on the 10th day to the respective groups. Blood and kidney samples were collected for the estimation of renal function, histology, the determination of oxidative stress, and the measurement of pro-inflammatory cytokines and markers of apoptosis. The results demonstrated that CP significantly elevated the levels of serum creatinine (Cr), blood urea nitrogen (BUN), and uric acid (UA) while it suppressed the renal markers of oxidative stress including glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) and increased malondialdehyde (MDA) content. In addition, CP up-regulated the markers of pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α in the kidney and induced apoptosis by activating caspase cascade, which was observed as elevated levels of caspase-3 and −9. Two weeks of continuous treatment of ALSK 25 mg/kg significantly decreased the levels of serum Cr, BUN, UA and ameliorated histological damage in CP-treated animals. ALSK increased the antioxidant defense (increased renal GSH, SOD, and CAT levels while MDA content was suppressed) against CP. ALSK also significantly decreased the levels of IL-1β, IL-6, and TNF-α and prevented apoptosis by reversing the increased levels of caspase-3 and −9 by CP. Therefore, it may be concluded that ALSK has a protective role against CP-induced nephrotoxicity in rats.

Keywords:

• Aliskiren
• cisplatin
• nephrotoxicity
• oxidative stress
• cytokines
• apoptosis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Authors are thankful to the Deanship of Scientific Research, Jazan University, Saudi Arabia, for providing financial assistance [Research Grant no. WAED-15–40] to carry out this research work.