Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (8): Protective effect of pyridoxal-5'-phosphate against tobramycin nephrotoxicity.
We investigated the effect of pyridoxal-5'-phosphate (PALP) on tobramycin (TOB)-induced nephrotoxicity in rats. Paper electrophoretic analysis showed that in the mixture of TOB and PALP, the spot corresponding to TOB alone almost disappeared and the spot associated with TOB overlapped with that associated with PALP, although the spots of TOB alone and PALP alone were observed as single spots on the cathode and anode sides, respectively. The overlapping of both compounds indicated that TOB could directly interact with PALP in vitro. In the assay of TOB binding to renal brush border membranes (BBMs), PALP significantly inhibited the binding of TOB to BBMs by interacting with TOB outside of BBMs vesicles. Intrarenal TOB levels in rats receiving TOB and PALP were lower than those in rats given TOB alone. Combination with PALP markedly suppressed the urinary protein content, urinary N-acetyl-beta-D-glucosaminidase activity and blood urea nitrogen content elevated by TOB, and also reduced the degree of TOB-induced renal tubular cell necrosis. These results indicate that PALP protects the rat kidneys from TOB-induced nephrotoxicity and that the protective effect of PALP may be due to the reduced intrarenal TOB concentration and less binding to TOB to BBMs induced by the interaction of PALP with TOB.
Kojima
R
R
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Ito
M
M
Suzuki
Y
Y
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D004590:Electrophoresis, Paper; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014031:Tobramycin / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity
D000900:Anti-Bacterial Agents; D011732:Pyridoxal Phosphate; D014031:Tobramycin