l‐carnitine ameliorates gentamicin‐induced renal injury in rats

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2002-12, Vol.17 (12), p.2122-2131
• Main Authors: Kopple, Joel D., Ding, Hu, Letoha, Annamaria, Ivanyi, Bela, Qing, David Pei‐Yuan, Dux, Lázló, Wang, Hui‐Yuan, Sonkodi, Sandor
• Format: Article
• Language: English
• Subjects: acute renal failure; acute tubular necrosis; Animals; Biological and medical sciences; carnitine; Carnitine - administration & dosage; Carnitine - pharmacology; Dose-Response Relationship, Drug; Drug Administration Schedule; gentamicin; gentamicin nephrotoxicity; Gentamicins - adverse effects; Injections, Subcutaneous; Kidney - drug effects; Kidney - pathology; Kidney - physiopathology; Kidney Cortex; kidney disease; Kidney Diseases - chemically induced; Kidney Diseases - pathology; Kidney Diseases - physiopathology; Kidney Diseases - prevention & control; Kidney Tubular Necrosis, Acute - pathology; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Urinary system
• ISSN: 0931-0509; 1460-2385; 1460-2385
• DOI: 10.1093/ndt/17.12.2122

Background. This study examined whether administration of l‐carnitine ameliorates gentamicin‐induced renal injury in rats. Methods. Male Sprague–Dawley rats were assigned to one of seven treatment groups: group A (control) rats were given normal saline injections daily for 8 consecutive days; group B, C and D rats were given gentamicin injections, 50 mg/kg body weight/day daily for 8 consecutive days; and group E, F and G rats were given gentamicin injections, 80 mg/kg/day daily for 8 consecutive days. Starting 4 days before these injections, all groups were given additional injections, for 12 consecutive days, of normal saline (groups A, B and E) or l‐carnitine at 40 mg/kg (groups C and F) or 200 mg/kg (groups D and G). Histological scoring of renal cortical pathology was performed after day 12. Results. Among rats injected with gentamicin 50 mg/kg/day, those given either 40 or 200 mg/kg/day of l‐carnitine had higher creatinine clearances at day 12 than the rats not given carnitine. In the rats given 80 mg/kg gentamicin and no carnitine, renal function tended to be lower than in controls. At day 12, the rats given gentamicin 80 mg/kg and l‐carnitine 200 mg/kg/day, compared with rats given gentamicin 80 mg/kg and no carnitine, displayed lower serum urea and probably creatinine concentrations, and higher creatinine clearances, and their serum urea was not different from control (group A) rats. Both doses of gentamicin induced renal cortical histopathology. Changes were milder with gentamicin 50 mg/kg/day, and l‐carnitine, particularly at 200 mg/kg/day, ameliorated the severity of renal pathology induced by both gentamicin doses. In rats given gentamicin 80 mg/kg/day, the animals treated with carnitine 200 mg/kg/day had significantly less severe proximal tubular necrosis and significantly greater mild proximal tubular necrosis compared with rats receiving l‐carnitine 40 mg/kg/day or no carnitine. Conclusions. In rats receiving gentamicin, daily l‐carnitine injections, particularly at 200 mg/kg/day, ameliorate the severity of renal cortical proximal tubular necrosis and maintain greater renal function.