Involvement of NOX-4/JAK/STAT pathway in the protective effect of aprepitant against diclofenac-induced renal toxicity

Autor: Heba M. Hafez, Shaimaa Waz, Rehab Ahmed Rifaai, Mervat Z. Mohamed
Rok vydání: 2021
Předmět:
Zdroj: Life sciences. 294
ISSN: 1879-0631
Popis: Aprepitant, a neurokinin-1 (NK1) receptor antagonist, is a clinically approved anti-emetic drug. Recently, inhibition of the NK1 receptor has been reported as a potential nephroprotective strategy. We aimed to assess the pharmacological mechanisms of aprepitant against diclofenac (DIC)-induced renal toxicity.An in vivo study was conducted using twenty-four male Wistar rats, divided into 4 groups. Aprepitant was administered for 5 days (5 mg/kg/day) with or without DIC which was given on the 4th and 5th days (50 mg/kg, i.p.). At the end of the study, renal function biomarkers, renal oxidative parameters, prostaglandin E (PGE-2), and NADPH oxidase (NOX-4) were measured. Histopathological changes as well as expression of renal inflammatory and apoptotic markers (tumor necrosis factor alpha (TNF-α) and caspase-3) were investigated.DIC caused significant renal damage, as evidenced by deterioration of renal functions, oxidative stress, inflammatory and apoptotic markers, and confirmed by histopathological findings. Pretreatment with aprepitant successfully ameliorated and improved all biochemical and molecular parameters induced by DIC. Moreover, aprepitant restored the decrease in renal PGE-2 concentration and inhibited DIC-activated Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling in renal tissues.The protective effect of aprepitant is possibly attributed to its anti-oxidant and anti-inflammatory roles via the NOX-4/JAK/STAT pathway.
Databáze: OpenAIRE
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