Drug- induced kidney injury is considered as a dangerous condition caused morbidity and mortality and most notably Vancomycin induced nephrotoxicity via oxidative stress, inflammatory insult and apoptosis.
our investigation was applied to assess the potential ameliorative effect of Carvacrol against vancomycin- triggered nephrotoxicity.
Male Sprague-Dawley rats were allocated into 5 groups: Normal control group, DMSO; a vehicle for carvacrol group, Group of animals given carvacrol 50 mg/kg/day orally, Group of rats challenged with intraperitoneal vancomycin 200mg/kg/day and group co-treated with carvacrol and vancomycin as previously mentioned and all treatments were applied for 7 continuous days.
Vancomycin caused nephrotoxicity which revealed as elevated levels of Urea, Creatinine, kidney injury molecule.1 (KIM1) and Cystatin C and confirmed histologically by degenerative changes in renal histo-architecture. Vancomycin enhanced protein expression of some inflammatory markers as tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and nuclear factor kappa B (NF-κB) along with down-regulation of protein expression of nuclear factor kappa B inhibitory protein (IKBβ). Likewise, it caused oxidative stress via down-regulation of nuclear factor erythroid 2–related factor 2 (Nrf2), heamoxygenase-1(HO-1) and glutathione (GSH) but increased Malondialdehyde (MDA) and Myeloperoxidase (MPO) levels. Also vancomycin caused apoptosis by increasing Bax gene expression together with decreasing Bcl2 gene expression. On contras, Carvacrol mitigated vancomycin induced kidney injury by restoration of kidney architecture and modulation of the inflammation, oxidative stress and apoptosis.
This study discloses that carvacrol suppresses vancomycin-induced nephrotoxicity through its anti-inflammatory, anti-oxidative stress and anti-apoptotic actions via Nrf2/HO-1, IKBβ/ NF-κB and Bax -Bcl2 pathways.