Gliclazide attenuates cisplatin-induced nephrotoxicity through inhibiting NF-κB and caspase-3 activity.

Abstract:

:Cisplatin (CP), as a chemotherapeutic drug, causes nephrotoxicity that has limited the clinical utility of CP. Gliclazide (GLZ), as an antihyperglycemic drug, at low dose has antioxidant property. In this study, we aimed to investigate the protective effect of GLZ against CP-induced acute renal injury. Sixty-four BALB/c mice were randomly divided into eight groups. The groups were included as control, GLZ (5, 10, and 25 mg/kg), CP, and GLZ (5, 10, and 25 mg/kg) + CP. Renal function markers (serum creatinine and blood urea nitrogen), oxidative stress markers (malondialdehyde and glutathione), apoptotic marker (caspase-3), and NF-κB were histopathologically evaluated. The results of our study showed that increased urea and creatinine were evidence of CP-induced nephrotoxicity. Histopathological examination revealed tubular epithelial and Bowman degeneration, edema, and cytoplasmic vacuolation in renal tissue structure. Administration of GLZ reduced oxidative stress, caspase-3, and NF-κB activity, and improved kidney function markers in CP-treated mice compared with CP alone group. Also, we observed that the histological tissue structure of the kidney was maintained. GLZ at dose of 25 mg/kg had higher protective effect as compared with other doses. Overall, our study suggests that GLZ with antioxidant, antiapoptotic, and anti-inflammatory properties may be a promising new therapeutic agent to prevent CP-induced nephrotoxicity.

journal_name

IUBMB Life

journal_title

IUBMB life

authors

Taghizadeh F,Hosseinimehr SJ,Zargari M,Karimpour Malekshah A,Talebpour Amiri FB

doi

10.1002/iub.2342

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

2024-2033

issue

9

eissn

1521-6543

issn

1521-6551

journal_volume

72

pub_type

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