Inhibition of gentamicin-induced nephrotoxicity by pyridoxal-5'-phosphate in the rat.
Daily s.c. injection of gentamicin at either 100 mg/kg for 4 days or 60 mg/kg for 2 weeks produced nephrotoxicity in the adult rat as judged by an increase in urinary excretion of beta-galactosidase, beta-glucuronidase and beta-N-acetylglucosaminidase. The observed enzymuria was associated with significant elevation in total renal phospholipid, phosphatidylinositol, phosphatidylcholine and phosphatidylserine. In addition, gentamicin decreased the activities of renal cortical Na+-K+-adenosine triphosphatase, alkaline phosphatase as well as phospholipase C. Pyridoxal-5'-phosphate (250 mg/kg/day) administered i.p. for 4 or 14 days did not markedly alter the metabolic markers of kidney function. In rats simultaneously given pyridoxal-5'-phosphate and gentamicin for 4 days the vitamin failed to prevent either the antibiotic-induced decrease in renal phospholipase C and alkaline phosphatase or the increase in total renal phospholipid, phosphatidylinositol, phosphatidylcholine and phosphatidylserine. However, simultaneous pyridoxal-5'-phosphate and aminoglycoside treatment for 2 weeks proved effective in blockade of the gentamicin-induced kidney phospholipidosis, elevation in urinary beta-galactosidase, beta-glucuronidase and beta-N-acetylglucosaminidase, as well as reduction in renal phospholipase C and alkaline phosphatase. The gentamicin-induced nephrotoxicity was associated with a decrease in renal pyridoxal-5'-phosphate levels. In the simultaneous 4-day-treated rat the renal concentration of pyridoxal-5'-phosphate returned to approximate control values, whereas after 2 weeks the level of vitamin B6 was approximately 2-fold higher than control. Although pyridoxal-5'-phosphate in the simultaneous group lowered kidney gentamicin content by 40% after 4 or 14 days, protection from aminoglycoside-induced nephrotoxicity was apparent only after 2 weeks in our study.(ABSTRACT TRUNCATED AT 250 WORDS)
Kacew
S
S
Department of Pharmacology, University of Ottawa, Ontario, Canada.
D000818:Animals; D005839:Gentamicins / Q000378:metabolism / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D010738:Type C Phospholipases / Q000032:analysis; D001616:beta-Galactosidase / Q000652:urine
D005839:Gentamicins; D010743:Phospholipids; D011732:Pyridoxal Phosphate; D009568:Nitrendipine; D010738:Type C Phospholipases; D001616:beta-Galactosidase