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Mechanism Involved in Fortification by Berberine in CDDP-Induced Nephrotoxicity

[ Vol. 13 , Issue. 4 ]

Author(s):

Vipin Kumar Verma, Salma Malik, Ekta Mutneja, Anil Kumar Sahu, Kumari Rupashi, Amit Kumar Dinda, Dharamvir Singh Arya and Jagriti Bhatia*   Pages 342 - 352 ( 11 )

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.

Affiliation:

Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi, Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi, Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi, Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi, Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi, Department of Pathology, All India Institute of Medical Sciences, New Delhi-110029, Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi, Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi



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