Antioxidant levels in the rat brain after nitric oxide synthase inhibition: a preliminary report.
Protective effects of NOS inhibitors and free radical scavengers in cerebral ischemia are well documented. The present study was undertaken to determine the possible effects of NOS inhibition on brain antioxidants. Levels of both enzymatic [glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD)] and non-enzymatic [reduced glutathione (GSH)] antioxidants following nitric oxide synthase (NOS) inhibition by N(G)-nitro-L-arginine methyl ester (L-NAME), D-NAME or 7-nitroindazole (7-NI) have been investigated. NOS activity and antioxidant levels in the rat cerebellum and medulla were estimated 1 h after treatment with L-NAME (10, 30 and 100 mg/kg, i.p.), D-NAME (100 mg/kg, i.p.) or 7-NI (25 mg/kg, i.p.). L-NAME and 7-NI inhibited NOS activity in a dose-dependent manner. D-NAME also exhibited significant NOS inhibition. The activity of SOD and the GSH level remained unaltered following NOS inhibition. However, L-NAME and D-NAME at 100 mg/kg attenuated GPx activity in the cerebellum, though 7-NI had no effect. L-NAME inhibited catalase activity in medulla only at 30 mg/kg, but had no effect in cerebellum. However, 7-NI (25 mg/kg), D-NAME and L-NAME at 100 mg/kg did not affect catalase activity in the rat brain. Thus, NOS inhibition by the three agents did not have major effects on brain antioxidant levels.
Barthwal
M K
MK
Pharmacology Division, Central Drug Research Institute, Lucknow, India.
Srivastava
N
N
Nag
D
D
Seth
P K
PK
Srimal
R C
RC
Dikshit
M
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013482:Superoxide Dismutase / Q000378:metabolism*
D000975:Antioxidants; D004791:Enzyme Inhibitors; D007191:Indazoles; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005978:Glutathione; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester