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.