Renoprotective effect of celecoxib against gentamicin-induced nephrotoxicity through suppressing NFκB and caspase-3 signaling pathways in rats.
Chem Biol Interact
; 315: 108863, 2020 Jan 05.
Article
em En
| MEDLINE
| ID: mdl-31628940
ABSTRACT
Gentamicin-induced nephrotoxicity has been well documented, although the causing mechanisms and preventative measures need further investigation. The current study aimed to explore the potential protective impacts of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on gentamicin-induced nephrotoxicity and the potential mechanisms in rats. Rats were randomly divided into four groups as follows group1 normal control, group 2 received gentamicin only (100â¯mg/kg intraperitoneally), group 3 concurrently received gentamicin and celecoxib (30â¯mg/kg, orally) and group 4 received celecoxib. Celecoxib administration decreased gentamicin-induced rise in kidney weight, renal somatic index (RSI), blood urea nitrogen (BUN), serum creatinine (Cr), protein in urine, lactate dehydrogenase (LDH), nitric oxide (NOx), meanwhile, it increased serum albumin, urine Cr level and creatinine clearance (CCr), increased the renal endogenous antioxidant status, revealed by decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) and reduced glutathione (GSH). Gentamicin-induced elevated nuclear factor kappa B-P65 subunit (NFκB-p65), tumor necrosis factor-alpha (TNF-α) and apoptotic markers (tumor suppressor protein (p53) and caspase-3) protein levels were significantly decreased upon celecoxib treatment. Moreover, celecoxib suppressed renal myeloperoxidase (MPO) activity and posed improvement of histological features. In immunohistochemistry, celecoxib-treated rats showed decreased immunoreactivity against COX-2 in tubular cells and a mild positive immunoreactivity against heat shock protein 70 (HSP70) in renal interstitial cells. These findings propose that celecoxib treatment mitigates renal dysfunction via decreasing renal inflammation, oxidative/nitrosative stress, and apoptosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
NF-kappa B
/
Substâncias Protetoras
/
Caspase 3
/
Celecoxib
/
Rim
/
Nefropatias
Limite:
Animals
Idioma:
En
Revista:
Chem Biol Interact
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Egito