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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Research Article

Mechanism Involved in Fortification by Berberine in CDDP-Induced Nephrotoxicity

Author(s): Vipin K. Verma, Salma Malik, Ekta Mutneja, Anil K. Sahu, Kumari Rupashi, Amit K. Dinda, Dharamvir S. Arya and Jagriti Bhatia*

Volume 13, Issue 4, 2020

Page: [342 - 352] Pages: 11

DOI: 10.2174/1874467213666200220142202

Price: $65

Abstract

Background: The activation of Nrf2/HO-1 pathway has been shown to protect against cisplatin- induced nephrotoxicity by reducing oxidative stress. Berberine (Ber), an isoquinoline 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 intraperitoneal injection of cisplatin (8 mg/kg) was injected on 7th day to induced nephrotoxicity. On 10th day, rats were sacrificed, the kidney was removed and stored for the estimation of various parameters.

Results: As compared to cisplatin-control group, Ber pretreatment 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 mediated 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.

Keywords: CDDP, Berberine, Nrf2/HO-1, PARP, JNK/p38 MAPK, nephrotoxicity.

Graphical Abstract

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