Modulating platelet-activating factor by rupatadine attenuates gentamicin-induced nephrotoxicity in rats via...

Gentamicin (GEN) is a commonly prescribed antibiotic for Gram-negative bacterial infections. One of the most common adverse consequences of it is renal damage which is developed in 30% of individuals receiving GEN for over 7 days. For the first time, we attempted to examine the reno-protective activity of rupatadine (RUP) on GEN-induced renal injury in rats. Renal damage was established by GEN in male Wistar rats. Histopathological analysis and kidney function panel were assessed. Levels of MDA, catalase, and SOD were detected using the colorimetric method. ELISA was utilized to assess the renal levels of IL-1β and TNF-α. qRT-PCR assessed mRNA levels of Bax and Bcl-2. Protein expression of Nrf-2, NF-κB, and caspase 3 were evaluated using Western blotting. GEN resulted in renal malfunction, high serum levels of cystatin C and BUN, increased renal levels of MDA, TNF-α, and IL-1β, decreased SOD and catalase activities, stimulated renal activation of NF-κB, and caspase 3 as well as inhibited the Nrf-2 protein expression, and upregulated Bax gene expression while it suppressed Bcl-2 gene expression. Conversely, RUP administration markedly attenuated the nephrotoxicity of GEN. RUP suppressed the levels of the proinflammatory mediators, inactivated the renal NF-κB and caspase 3 proteins, declined renal mRNA levels of Bax gene, and upregulated the renal mRNA level of the Bcl-2 gene. In conclusion, RUP mitigated GEN-caused renal damage by suppressing proinflammatory markers, mitigating apoptosis via repressing the intracellular PAF/NF-κB/caspase-3 pathway and upregulating Nrf2/HO-1 signaling cascades.