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.

Protective effects of sinapic acid against cyclophosphamide‐induced testicular toxicity via inhibiting oxidative stress, caspase‐3 and NF‐kB activity in BALB/c mice

“…The glutathione (GSH) level in the testis was calculated by spectrophotometer with 5,5′‐dithiobis‐2‐nitrobenzoic acid (DTNB) as an marker at 412 nm and expressed as μmol/gr tissue (Taghizadeh et al., 2020).…”

“…Then, sections were incubated with primary antibodies (anti‐rabbit polyclonal antibody, 1:75, v/v, Abcam, lat: GR224831‐2 and 831054 ab7970‐1) overnight. After incubation with secondary antibody conjugated with horseradish peroxidase (Mouse and Rabbit Specific HRP/DAB, Abcam, Lat: GR2623314‐4) for 2 hr, sections were incubated with diaminobenzidine tetrahydrochloride for 5 min (Taghizadeh et al., 2020). Then, the slides were dehydrated and mounted.…”

Alleviation of cisplatin‐induced hepatotoxicity by gliclazide: Involvement of oxidative stress and caspase‐3 activity

“…After incubation with secondary antibody conjugated with horseradish peroxidase (Mouse and Rabbit Specific HRP/DAB, Abcam, Lat: GR2623314‐4) for 2 h, immunohistochemical staining was carried out by incubation with diaminobenzidine tetrahydrochloride for 5 min. Then, the slides were dehydrated and mounted 20 . The primary antibody was omitted for negative controls.…”

“…Then, the slides were dehydrated and mounted. 20 The primary antibody was omitted for negative controls. For the quantitative analysis, immunohistochemical photomicrographs were estimated by densitometry using MacBiophotonics ImageJ 1.41asoftware in 5 fields/each section in all groups.…”

Ameliorative Effects of Gallic Acid on Cisplatin-Induced Nephrotoxicity in Rat Variations of Biochemistry, Histopathology, and Gene Expression

“…Investigations have also presented that Cisplatin induces the tumor-suppressor protein p53. This affects apoptosis via the receptor-tumor necrosis factor interaction, and Caspases that cause mitochondrial disorder also affect the calcium signaling by stress on the endoplasmic reticulum [9,13,14].…”