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Protective effect of ebselen, a selenoorganic drug, against gentamicin-induced renal damage in rats.
Basic Clin Pharmacol Toxicol. 2006 Sep; 99(3):267-72.BC

Abstract

Gentamicin is an antibiotic that is widely used against serious and life-threatening gram-negative infections. However, its clinical use is limited by its nephrotoxicity. Oxidative stress and nitrosative stress are reported to play important role in gentamicin nephrotoxicity. In the present study we investigated whether ebselen, an inhibitor of oxidative stress and nitrosative stress prevents or reduces gentamicin-induced renal damage in the rat. For this purpose male Wistar rats were divided into five groups and treated as follows. Group 1 (control group): dimethyl sulphoxide, intraperitoneally, Group 2: Gentamicin 100 mg/kg b.wt. subcutaneously, Group 3: 5 mg/g b.wt. ebselen intraperitoneally, Group 4: 2.5 mg/kg b.wt. ebselen followed by 100 mg/kg b.wt. gentamicin subcutaneously one hour later, and Group 5: 5 mg/kg b.wt. of ebselen followed by 100 mg/kg b.wt. gentamicin one hour later for four consecutive days. Nephrotoxicity was evaluated histopathologically by light microscopy, and biochemically by the measurement of the plasma creatinine and urea levels. Parameters of oxidative stress such as reduced glutathione, malondialdehyde, and activities of superoxide dismutase and glutathione peroxidase were measured in the kidney. Serum nitrite and nitrate were measured as indicators of nitrosative stress. Treatment of rats with gentamicin resulted in statistically significant reduction in reduced glutathione levels (51%) and the activities of antioxidant enzymes superoxide dismutase (56%) and glutathione peroxidase (39%) as compared with the controls in the kidneys. Renal malondialdehyde level was increased significantly (43%) as compared with the controls. Plasma creatinine levels, urea levels and nitrite levels were significantly increased (4, 4.5 and 160% times respectively) as compared with the controls. Histologically, damage to the renal cortex and medulla was observed moderate to severe tubular necrosis and glomerular congestion. Pretreatment with 2.5 mg/kg b.wt. ebselen prevented gentamicin induced damage to medulla; however, renal cortex showed mild damage and biochemically indicators of oxidative stress and nitrosative stress were significantly reduced. Pretreatment with 5 mg/kg b.wt. ebselen prevented gentamicin-induced oxidative damage and nitrosative damage and renal damage almost completely in 78% of the rats, in the other 22% of the rats, ebselen pretreatment reduced gentamicin-induced renal damage. The results of the present study suggest that ebselen may be useful as a nephroprotective agent.

Authors+Show Affiliations

Department of Biochemistry, Christian Medical College, Bagayam, Vellor 632002, Tamil Nadu, India.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16930301

Citation

Dhanarajan, R, et al. "Protective Effect of Ebselen, a Selenoorganic Drug, Against Gentamicin-induced Renal Damage in Rats." Basic & Clinical Pharmacology & Toxicology, vol. 99, no. 3, 2006, pp. 267-72.
Dhanarajan R, Abraham P, Isaac B. Protective effect of ebselen, a selenoorganic drug, against gentamicin-induced renal damage in rats. Basic Clin Pharmacol Toxicol. 2006;99(3):267-72.
Dhanarajan, R., Abraham, P., & Isaac, B. (2006). Protective effect of ebselen, a selenoorganic drug, against gentamicin-induced renal damage in rats. Basic & Clinical Pharmacology & Toxicology, 99(3), 267-72.
Dhanarajan R, Abraham P, Isaac B. Protective Effect of Ebselen, a Selenoorganic Drug, Against Gentamicin-induced Renal Damage in Rats. Basic Clin Pharmacol Toxicol. 2006;99(3):267-72. PubMed PMID: 16930301.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effect of ebselen, a selenoorganic drug, against gentamicin-induced renal damage in rats. AU - Dhanarajan,R, AU - Abraham,Premila, AU - Isaac,Bina, PY - 2006/8/26/pubmed PY - 2007/2/14/medline PY - 2006/8/26/entrez SP - 267 EP - 72 JF - Basic & clinical pharmacology & toxicology JO - Basic Clin Pharmacol Toxicol VL - 99 IS - 3 N2 - Gentamicin is an antibiotic that is widely used against serious and life-threatening gram-negative infections. However, its clinical use is limited by its nephrotoxicity. Oxidative stress and nitrosative stress are reported to play important role in gentamicin nephrotoxicity. In the present study we investigated whether ebselen, an inhibitor of oxidative stress and nitrosative stress prevents or reduces gentamicin-induced renal damage in the rat. For this purpose male Wistar rats were divided into five groups and treated as follows. Group 1 (control group): dimethyl sulphoxide, intraperitoneally, Group 2: Gentamicin 100 mg/kg b.wt. subcutaneously, Group 3: 5 mg/g b.wt. ebselen intraperitoneally, Group 4: 2.5 mg/kg b.wt. ebselen followed by 100 mg/kg b.wt. gentamicin subcutaneously one hour later, and Group 5: 5 mg/kg b.wt. of ebselen followed by 100 mg/kg b.wt. gentamicin one hour later for four consecutive days. Nephrotoxicity was evaluated histopathologically by light microscopy, and biochemically by the measurement of the plasma creatinine and urea levels. Parameters of oxidative stress such as reduced glutathione, malondialdehyde, and activities of superoxide dismutase and glutathione peroxidase were measured in the kidney. Serum nitrite and nitrate were measured as indicators of nitrosative stress. Treatment of rats with gentamicin resulted in statistically significant reduction in reduced glutathione levels (51%) and the activities of antioxidant enzymes superoxide dismutase (56%) and glutathione peroxidase (39%) as compared with the controls in the kidneys. Renal malondialdehyde level was increased significantly (43%) as compared with the controls. Plasma creatinine levels, urea levels and nitrite levels were significantly increased (4, 4.5 and 160% times respectively) as compared with the controls. Histologically, damage to the renal cortex and medulla was observed moderate to severe tubular necrosis and glomerular congestion. Pretreatment with 2.5 mg/kg b.wt. ebselen prevented gentamicin induced damage to medulla; however, renal cortex showed mild damage and biochemically indicators of oxidative stress and nitrosative stress were significantly reduced. Pretreatment with 5 mg/kg b.wt. ebselen prevented gentamicin-induced oxidative damage and nitrosative damage and renal damage almost completely in 78% of the rats, in the other 22% of the rats, ebselen pretreatment reduced gentamicin-induced renal damage. The results of the present study suggest that ebselen may be useful as a nephroprotective agent. SN - 1742-7835 UR - https://www.unboundmedicine.com/medline/citation/16930301/Protective_effect_of_ebselen_a_selenoorganic_drug_against_gentamicin_induced_renal_damage_in_rats_ L2 - https://doi.org/10.1111/j.1742-7843.2006.pto_474.x DB - PRIME DP - Unbound Medicine ER -