Formononetin Ameliorates Renal Dysfunction, Oxidative Stress, Inflammation, and Apoptosis and Upregulates Nrf2/HO-1 Signaling in a Rat Model of Gentamicin-Induced Nephrotoxicity

Abstract

Gentamicin (GEN) is a bactericidal aminoglycoside known to cause nephrotoxicity. Formononetin (FN) is a potent flavonoid that exhibits numerous promising pharmacological activities. In this study, we have assessed the nephroprotective efficacy of FN against GEN-induced renal injury in rats. Rats were orally administered with FN (60 mg/kg/day, for 2 weeks) and were co-treated with intraperitoneal (i.p.) injection of GEN (100 mg/kg/day) during the days 8–14. GEN-treated rats demonstrated increased urea and creatinine levels in serum associated with marked histopathological changes in the kidney. Malondialdehyde (MDA) and protein carbonyl contents were elevated, whereas glutathione concentration and catalase and superoxide dismutase activities were lowered in GEN-administered rats. The FN largely prevented tissue damage, attenuated renal function, reduced MDA and protein carbonyl, and enhanced antioxidant capacity in the kidney of GEN-administrated animals. The kidney of GEN-treated rats demonstrated elevated Bax and caspase-3 protein expression, accompanied by lowered Bcl-2 protein expression, an effect that FN attenuated. Moreover, FN treatment caused upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expression in renal tissue of GEN-intoxicated animals. Collectively, FN protects against GEN-caused renal damage via exhibiting antioxidant, anti-inflammatory, and antiapoptotic activities and augmenting Nrf2 signaling, suggesting FN as a promising agent for preventing drug-induced organ damage.

Zamzam Water Ameliorates Gentamicin-Induced Testicular Toxicity in a Rat Model via Targeting Sperm Parameters, Testicular Tissue Oxidative Insult, Inflammation, Apoptosis, and Pituitary-Gonadal Axis

“…Our results revealed significant (p < 0.001) downregulation in testicular Nrf2/HO-1 gene expression in the gentamicin group in relation to control rats. This result coincides with Althunibat et al [64], who reported that gentamicin administration downregulated immunoexpression of Nrf2 and HO-1 in a rat model of gentamicin-induced nephrotoxicity. Nrf2 is considered a redox-sensitive transcription factor that is sequestered by Keap-1 in the cytoplasm.…”

Hepato-protective effects of Montelukast against methotrexate-induced hepatotoxicity in rat model

“…Since these enzymes are found in the cytosol and released into the blood after liver damage, this spike is attributed to damaged liver cells. This outcomes was in agreement with the results reported by [38][39]. The elevation in Liver enzyme since they are located in the cytoplasm and released into the bloodstream following cellular damages signaling the development of hepatotoxicity, level has been linked to the damage to the structural integrity of the liver…”

Renoprotective and Oxidative Stress-Modulating Effects of Taxifolin against Cadmium-Induced Nephrotoxicity in Mice

“…Although activated by ROS under physiological conditions, Nrf2 downregulation has been reported under conditions of excessive and prolonged ROS [ 31 , 58 , 59 , 60 ]. Extensive evidence indicates that various naturally occurring compound-mediated Nrf2 activation can protect against drugs/chemicals-induced renal injury [ 58 , 59 , 61 ]. Several investigations have reported the role of Nrf2 in mediating the protective role of TA [ 20 , 62 ].…”

“…Indeed, Nrf2 modulates the response to OS by regulating the expression of numerous genes, including ferritin and HO-1, supported by the antioxidant responses [ 63 ]. Accordingly, a previous study showed that TA prevented skin cancer by inducing Nrf2 expression and downstream target genes in JB6 P+ cells via the CpG demethylation process [ 61 ]. Furthermore, Xie et al [ 62 ] reported that TA could protect human RPE cells against OS-induced apoptosis via activating the expression of Nrf2 by facilitating its translocation to the nucleus.…”