Animal studies on the reduction of aminoglycoside-induced nephrotoxicity by D-glucaro-1,5-lactam.
We studied the effect of D-glucaro-1,5-lactam on aminoglycoside-induced nephrotoxicity in rats. Parameters of nephrotoxicity were urinary excretion of tubule cells and malate dehydrogenase. When given in appropriate doses, either i. m. or via an oral tube, D-glucaro-1,5-lactam significantly reduced the excretion of cells and enzymes during the administration of gentamicin, tobramycin, dibekacin, netilmicin and ribostamycin. It did not impair the therapeutic efficacy of ribostamycin in the experimental treatment of acute pyelonephritis in rats. The protective effect of D-glucaro-1,5-lactam could be ascribed to its inhibition of beta-glucuronidase, an enzyme which is located in renal lysosomes and which is activated by aminoglycosides.
D000617:Aminoglycosides / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D005260:Female; D005937:Glucaric Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D005966:Glucuronidase / Q000037:antagonists & inhibitors; D007668:Kidney / Q000201:enzymology; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control* / Q000652:urine; D008291:Malate Dehydrogenase / Q000652:urine; D011704:Pyelonephritis / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D013400:Sugar Acids / Q000627:therapeutic use*
D000617:Aminoglycosides; D013400:Sugar Acids; C001845:D-glucaro-delta-lactam; D008291:Malate Dehydrogenase; D005966:Glucuronidase; D005937:Glucaric Acid