Title:Mechanism Involved in Fortification by Berberine in CDDP-Induced Nephrotoxicity
Volume: 13
Author(s): Vipin K. Verma, Salma Malik, Ekta Mutneja, Anil K. Sahu, Kumari Rupashi, Amit K. Dinda, Dharamvir S. Arya and Jagriti Bhatia*
Affiliation:
- Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi,India
Keywords:
CDDP, Berberine, Nrf2/HO-1, PARP, JNK/p38 MAPK, nephrotoxicity.
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.
