Carvedilol and rosuvastatin mitigate nephrotoxicity of sodium valproate through activation of Nrf2 pathway in rats

Nourhan Abd El-Fattah, Ahmed Eid, Heba Zaky, Hebatalla Ibrahim
2021 Azhar International Journal of Pharmaceutical and Medical Sciences  
Sodium valproate, one of the most widely used antiepileptic drugs, has been noted to induce nephrotoxicity through elevation of oxidative stress. Carvedilol, a non-specific beta-adrenergic blocker, and rosuvastatin, an anti-hyperlipidemic, possess antioxidant characteristics. This study was planned to estimate the promising defensive impacts of Carvedilol and/or rosuvastatin against valproate-induced nephrotoxicity. It was revealed that sodium valproate (SVP) markedly boosted serum creatinine
more » ... Cr) and blood urea nitrogen (BUN). Moreover, glutathione level (GSH) was decreased with a concomitant elevation in renal malondialdehyde level (MDA) and inducible nitric oxide synthase activities (iNOS). After SVP treatment, there were significant elevations in renal tumor necrosis factor-alpha (TNF-𝛼) and nuclear factor-kappa B (NF-κB). Additionally, SVP-induced suppression of nuclear related factor 2 (Nrf2) pathways. Furthermore, histopathological examination showed prodigious inflammation, necrosis, congestion and degeneration. Coadministration of Carvedilol and/or rosuvastatin mitigated nephrotoxicity induced by SVP. Using the combination of Carvedilol and rosuvastatin presented additional intense renal protective effect when compared with each alone.
doi:10.21608/aijpms.2021.206679 fatcat:my7ksg54w5garinrvnwfqteoci