Mechanism involved in fortification by berberine in CDDP-induced nephrotoxicity

BACKGROUND: Activation of Nrf2/HO-1 pathway has been shown to protect against cisplatin-induced nephrotoxicity by reducing oxidative stress. Berberine (Ber), an isoquinolone alkaloid, has demonstrated antioxidant, anti-inflammatory and anti-apoptotic activities in various experimental models. AIM: To check the effect of Ber on cisplatin-induced nephrotoxicity and to explore the involved mechanism. METHODS: Adult male Wistar rats were divided into 6 groups: Normal, cisplatin-control, treatment groups and per se group. Normal saline and Ber (20, 40 and 80 mg/kg; p.o.) was administered to rats for 10 days. A single intraperitonealinjection of cisplatin (8mg/kg) was injected on 7th day to induced nephrotoxicity. On 10th day, rats were sacrificed, kidney was removed and stored for estimation of various parameters. RESULTS: As compared to cisplatin-control group, Berpretreatment improved renal function system and preserved renal architecture. It also diminished oxidative stress by upregulating the expression of Nrf2/HO-1 proteins. In addition, Ber attenuated the cisplatin medicated inflammation and apoptosis. Furthermore, it also reduced the phosphorylation of p38/JNK and PARP/Beclin-1 expression in the kidney. CONCLUSION: Ber attenuated renal injury by activating Nrf2/HO-1 and inhibiting JNK/p38MAPKs/PARP/Beclin-1 expression which prevented oxidative stress, inflammation, apoptosis and autophagy in renal tissue.