Effects of nicotinamide and its isomers on iron-induced renal damage.
The effects of three isomers of pyridinecarboxamide (picolinamide (2-pyridinecarboxamide), nicotinamide (3-pyridinecarboxamide) and isonicotinamide (4-pyridinecarboxamide)) on iron-induced renal damage were studied. Pyridinecarboxamide (250 mg/kg body weight, ip) was administered 10 min before injection of ferric nitrilotriacetate (Fe(III)-NTA) (7.5 mgFe/kg body weight, ip). In picolinamide-treated rats, the renal tubular necrosis induced by Fe(III)-NTA was attenuated and serum creatinine did not increase. Picolinamide most efficiently suppressed renal lipid peroxidation in vivo-induced by Fe(III)-NTA. Non-heme iron levels in the kidneys after Fe(III)-NTA injection did not differ in groups to which pyridinecarboxamides were administered. To elucidate the protective effects of picolinamide, we studied the action of pyridinecarboxamides on lipid peroxidation and DNA damage in vitro. These isomers inhibited iron-induced lipid peroxidation of linolenic acid. Picolinamide had no effect on DNA damage, but nicotinamide and isonicotinamide promoted DNA damage by iron, especially when ascorbate was used as a reductant. None of these pyridinecarboxamide isomers changed the chlelate structure of Fe(III)-NTA as shown by electronic absorption spectra. Among the three isomers, picolinamide most effectively protected the kidneys against iron-induced renal damage, since it not only inhibited iron-induced lipid peroxidation, but also had little enhancing action on DNA damage by iron.
Kawabata
T
T
Department of Pathology, Okayama University Medical School, Japan.
Ogino
T
T
Mori
M
M
Awai
M
M
D000577:Amides / Q000494:pharmacology; D000818:Animals; D003404:Creatinine / Q000097:blood; D004249:DNA Damage; D005290:Ferric Compounds; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000517:prevention & control; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009536:Niacinamide / Q000494:pharmacology*; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives; D010848:Picolinic Acids / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000577:Amides; D005290:Ferric Compounds; D010848:Picolinic Acids; D009536:Niacinamide; C027681:isonicotinamide; D008315:Malondialdehyde; D003404:Creatinine; C003142:picolinamide; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate