Involvement of oxidative stress and toll-like receptor-4 signaling pathways in gentamicin-induced nephrotoxicity in male Sprague Dawley rats

Ethanolic Extracts of Grape and Guava Seeds Ameliorate Gentamicin Induced Acute Renal Injury in Rats

“…In the presence of a metal catalyst, the interaction between superoxide anion and hydrogen peroxide can form hydroxyl radicals. It has been reported that GM increases the production of hydroxyl radicals and causes the release of iron from renal cortical mitochondria [7][8][9][10][11]. Consistent with different previous investigations, the results of the present study show that GM caused a significant elevation in renal MDA levels and a noticeable drop in the activity of erythrocyte SOD and in the levels of blood and renal GSH.…”

“…It is proposed that antioxidant enzymes are suppressed by ROS, including O2 -, H2O2, and OHradicals. The suppressive effects of GM on the enzymatic antioxidants lead to ROS generation, which is considered one of the factors associated with GMinduced renal toxicity and dysfunction [8,50]. In this investigation, the upregulation of NF-κB in renal tissue of GM-treated rats is in accordance with the results of previous studies and reinforces the role of GM-derived inflammation as an underlying cause of alteration of the kidney, favoring the development of nephrotoxicity [10][11].…”

“…KIM-1, a type I transmembrane glycoprotein, is undetectable in the healthy kidney; nevertheless, upon renal injury, proximal convoluted tubules have a dramatically increased expression of KIM-1 [54]. The increment in serum activity of ALP observed in this study revealed that GM-induced oxidative stress damages in rats [7,8,10]. ALP is an endoplasmic reticulum marker.…”

“…Inflammation and oxidative stress are inextricably related because each enhances the other. In this context, oxidative stress invariably recruits inflammation through the activation of NF-κB, which is the general transcription factor for various proinflammatory cytokines, chemokines, and adhesion molecules [8][9][10]. A previous study demonstrated that increased NF-κB activation in GM-treated rats was followed by increased inflammatory substance synthesis.…”

“…The experimental data point to oxidative stress as a pivotal factor in GM-induced nephrotoxicity. GM intensifies the generation of reactive oxygen species (ROS) that cause cytotoxic consequences and promote lipid peroxidation, protein oxidation, and apoptosis [7,8]. Furthermore, the amplified ROS generation brought on by GM plays a crucial role in the onset of inflammation through NF-κB activation [9,10,11], which activates the target genes implicated in the inflammatory process, such as adhesion molecules, cytokines (TNF-α and IL-6), and inducible nitric oxide synthase (iNOS) [12].…”