title: [Effects of the calcium-channel blocker diltiazem on gentamicin-induced nephrotoxicity in rats].
abstract: Injection of diltiazem (40 mg/kg/d) to gentamicin (75 mg/kg/d = G 75 or 100 mg/kg/d = G 100) treated rats enhances aminoglycoside-induced nephrotoxicity. As a result of this combination, acute renal failure becomes systematic and is often irreversible. The lesion is of tubular origin and is characterized by a large increase in the urinary N-acetyl-beta-D-glucosaminidase (u-NAG) activity and its NAG-B isoenzyme level. The phenomenon is twice as marked with G 75 (u-NAG x 6.8, NAG-B x 2.2) as with G 100 (u-NAG x 3.1, NAG-B x 1.1). The effect seems to be attenuated if diltiazem is administered as a preventive treatment or in drinking water. As well as its diuretic properties, diltiazem may aggravate the renal toxicity of gentamicin by reducing the proximal tubular availability of calcium. Diltiazem inhibits reabsorption and behaves like a non-competitive inhibitor of calcium. This deficiency favours the proximal tubular binding and the non-specific penetration of gentamicin in the cytosol and cellular organelles (microsomes, mitochondria). The tubular toxic symptoms which ensure (inactivation of membranaceous enzyme, reduction of microsomal protein synthesis and ATP level, decreased of solute reabsorptive flux) lead in turn to proximal tubular necrosis and acute renal failure.
authors.affiliation: Laboratoire de Biochimie Médicale, CHU Saint-Jacques, Besançon.
authors.forename: R
authors.initials: R
authors.lastname: Gibey
authors.forename: J C
authors.initials: JC
authors.lastname: Henry
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D004110:Diltiazem / Q000627:therapeutic use*; D004347:Drug Interactions; D005839:Gentamicins / Q000506:poisoning*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005839:Gentamicins; D000118:Acetylglucosaminidase; D004110:Diltiazem
vernacular_title: Effets d'un inhibiteur des canaux calciques, le diltiazem sur la néphrotoxicité de la gentamicine chez le rat.