title: Protective effect of L-arginine on gentamicin-induced nephrotoxicity in rats.
abstract: BACKGROUND
  L-arginine has a protective effect on gentamicin-induced renal failure and it may decrease the tubular reabsorption of another cationic substance, gentamicin due to its cationic structure. The aim of this study is to compare the possible protective effects of L-arginine and its inactive isomer D-arginine on gentamicin-induced nephrotoxicity in rats.
  
  
  METHODS
  Wistar albino rats were housed in metabolic cages and assigned to six groups as: control group, gentamicin (100 mg/kg), gentamicin + L-arginine (2 g/l), gentamicin + D-arginine (2 g/l), gentamicin + L-arginine + Nv-nitro-L-arginine methyl ester (L-NAME) (100 mg/l) and gentamicin + D-arginine + L-NAME. Gentamicin was administered by subcutaneous injections and the other drugs were added in drinking water for seven consecutive days. The animals were killed by decapitation and intracardiac blood and urine samples were obtained on the seventh day. Blood urea nitrogen, serum creatinine, sodium, potassium, urine gamma glutamyl transferase, creatinine, sodium, potassium and gentamicin levels were measured using High Performance Liquid Chromatography (HPLC) technique.
  
  
  RESULTS
  Gentamicin treated group had significant increase in blood urea nitrogen, serum creatinine, fractional Na excretion and urine gamma glutamyl transferase levels, and significant decrease in creatinine clearance compared to the control group. L-arginine and D-arginine reversed these findings. L-NAME abolished the nephroprotective effect of L-arginine. The urinary levels of gentamicin were significantly increased in rats treated with L-arginine or D-arginine compared to those treated with gentamicin. L-arginine and D-arginine reversed the advanced degenerative changes due to gentamicin administration in histopathological examination.
  
  
  CONCLUSIONS
  Our study revealed the protective effect of L-arginine on gentamicin-induced nephrotoxicity, the contribution of the cationic feature of L-arginine, and the major role of NO in this protective effect.
authors.affiliation: Mersin University Medical Faculty Department of Medical Education, 33343 Yenisehir, Mersin, Turkey.
authors.forename: İbrahim
authors.initials: İ
authors.lastname: Başhan
authors.affiliation: Department of Pharmacology, Çukurova University Medical School, 01330, Balcali, Adana, Turkey.
authors.forename: Perihan
authors.initials: P
authors.lastname: Başhan
authors.affiliation: Department of Pharmacology, Çukurova University Medical School, 01330, Balcali, Adana, Turkey.
authors.forename: Mehmet Ata
authors.initials: MA
authors.lastname: Seçilmiş
authors.affiliation: Department of Pharmacology, Çukurova University Medical School, 01330, Balcali, Adana, Turkey.
authors.forename: Ergin
authors.initials: E
authors.lastname: Şingirik
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000652:urine; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D005839:Gentamicins / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000652:urine; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D011188:Potassium / Q000097:blood; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000097:blood
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D020011:Protective Agents; D001120:Arginine; D012964:Sodium; D003404:Creatinine; D011188:Potassium
keywords: D-arginine; HPLC; L-arginine; gentamicin; nephrotoxicity