Mohamed Katary1, Ahmad Salahuddin2. 1. Pharmacology and Toxicology Department, Faculty of Pharmacy, Damanhour University, Egypt. 2. Biochemistry Department, Faculty of Pharmacy, Damanhour University, Egypt. Electronic address: salahuddin@pharm.dmu.edu.eg.
Abstract
AIM: Gentamicin (GEN) is an aminoglycoside antibiotic employed in treatment of life-threatening gram-negative infections, but one of its major side effects is the induction of nephrotoxicity. Therefore, the aim of this work was to scrutinize the possible protective effect of gossypin against GEN-induced nephrotoxicity. METHOD: Rats were randomly divided into four groups. First group served as a control, second group was injected with gossypin (10mg/kg, orally) for 7days, third group was injected with GEN (80mg/kg, i.p.) and the fourth group was co-treated with GEN and gossypin for 7days. KEY FINDING: GEN-treated group showed kidney dysfunction as proteinuria excretion rate, podocalyxin excretion rates, renal monocyte chemoattractant protein-1 (MCP-1), blood urea nitrogen (BUN) and plasma creatinine were significantly increased as well as tubular degeneration occur. The significant decrease in renal reduced glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities and an increase in thiobarbituric acid reactive substances (TBARs) level, indicated that GEN-induced nephrotoxicity through oxidative stress reactions. Also, GEN up-regulated both gene expression and renal levels of inflammatory cytokines TNF-α and IL-6. On the other hand, concurrent treatment of gossypin plus GEN protected kidney tissues against nephrotoxic effects of GEN through elevated levels of renal GSH, SOD and CAT activities while decreased in renal TBARs level. In addition, gossypin down-regulated gene expression and renal levels of inflammatory cytokines TNF-α and IL-6 induced by GEN. SIGNIFICANCE: This study revealed that gossypin exerts protection against nephrotoxicity induced by gentamicin via its antioxidant activity.
AIM: Gentamicin (GEN) is an aminoglycoside antibiotic employed in treatment of life-threatening gram-negative infections, but one of its major side effects is the induction of nephrotoxicity. Therefore, the aim of this work was to scrutinize the possible protective effect of gossypin against GEN-induced nephrotoxicity. METHOD: Rats were randomly divided into four groups. First group served as a control, second group was injected with gossypin (10mg/kg, orally) for 7days, third group was injected with GEN (80mg/kg, i.p.) and the fourth group was co-treated with GEN and gossypin for 7days. KEY FINDING: GEN-treated group showed kidney dysfunction as proteinuria excretion rate, podocalyxin excretion rates, renal monocyte chemoattractant protein-1 (MCP-1), blood urea nitrogen (BUN) and plasma creatinine were significantly increased as well as tubular degeneration occur. The significant decrease in renal reduced glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities and an increase in thiobarbituric acid reactive substances (TBARs) level, indicated that GEN-induced nephrotoxicity through oxidative stress reactions. Also, GEN up-regulated both gene expression and renal levels of inflammatory cytokines TNF-α and IL-6. On the other hand, concurrent treatment of gossypin plus GEN protected kidney tissues against nephrotoxic effects of GEN through elevated levels of renal GSH, SOD and CAT activities while decreased in renal TBARs level. In addition, gossypin down-regulated gene expression and renal levels of inflammatory cytokines TNF-α and IL-6 induced by GEN. SIGNIFICANCE: This study revealed that gossypin exerts protection against nephrotoxicity induced by gentamicin via its antioxidant activity.
Authors: Félix Vargas; Paola Romecín; Ana I García-Guillén; Rosemary Wangesteen; Pablo Vargas-Tendero; M Dolores Paredes; Noemí M Atucha; Joaquín García-Estañ Journal: Front Physiol Date: 2018-04-24 Impact factor: 4.566