Celecoxib has Preventive and Therapeutic Benefits against Nephrotoxicity Caused by Gentamicin in Mice

Abstract

It’s crucial to comprehend the impact of oxidative stress and pro-inflammatory cytokines in the gentamicin-induced kidney injury mechanism. Celecoxib was administered orally either before or after intraperitoneal therapy with gentamicin in mice. The serum levels of creatinine (SCr), blood urea nitrogen (BUN), IL-6, and TNF-α were measured by ELISA test, as well as the levels of the kidney tissue malondialdehyde (MDA), and glutathione (GSH) were also estimated spectrophotometrically. The renal expression of nuclear factor-κB (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase 2 (COX-2) mRNAs were evaluated by qPCR. Histopathological evaluation and Immunohistochemical examination of kidney NF-κB, IL-6, and COX-2 were also, performed. Celecoxib successfully prevented gentamicin-induced kidney damage as indicated by reducing blood BUN, SCr, and tissue MDA levels and increasing renal tissue GSH levels as well as lowering the blood IL-6 and TNF-α in comparison to mice received gentamicin. Furthermore, celecoxib has inhibited COX-2, NF-κB, IL-6, and TNF-α expression in the renal tissue. It is noteworthy that celecoxib therapy after gentamicin administration brought about substantially the same results as celecoxib treatment before gentamicin injection in mice. Our results showed the role of celecoxib as a therapeutic tool for gentamicin-induced nephrotoxicity as well as raised its beneficial prophylactic role in this medical challenge by attenuating oxidative stress and inflammation.

Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney

“…It is noteworthy that 3D image reconstruction allowed for a visualization of the whole glomerulus, which is superior to the analysis of histology sections due to the asymmetric distribution of collapsed apoptotic cells and capillaries within the damaged glomerulus [ 45 ]. Functional studies in gentamicin-treated mice confirms renal impairment by elevated kidney function biomarkers, such as serum creatinine, blood urea nitrogen and urea together with increased cytokine levels, such as interleukin-6 and tumor necrosis factor-alpha (TNF-α) [ 46 , 47 ].…”

Punicalagin Opposes Gentamicin Nephrotoxicity in Rats: Role of Nrf2 and NF-κB Pathways

“…2 Nitrosative stress and enhanced generation of reactive nitrogen species (RNS) due to activation of inducible nitric oxide synthase (iNOS) are also involved in GEN nephrotoxicity. 3 Additionally, increased production of inflammatory cytokines, as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), was reported to participate in renal tubular cell injury caused by GEN. 4 The inflammatory mediators and ROS finally up-regulate the apoptotic pathways and caspase family of proteases, which induce renal cell apoptotic death. 5 Cellular responses to oxidative, inflammatory, and apoptotic insults are largely controlled by the fine balance between nuclear factor erythroid 2-related factor 2 (Nrf2), the anti-inflammatory pathway, and nuclear factor-κB (NF-κB), the proinflammatory pathway.…”