Effects of diphenhydramine and famotidine on lipid peroxidation and activities of antioxidant enzymes in different rat tissues.
The potential antioxidant activity of diphenhydramine (histamine H1-receptor antagonist) and famotidine (histamine H2 receptor antagonist) was studied. Diphenhydramine inhibited the spontaneous, Fe(II)-induced and Fe(II)/ascorbate-induced lipid peroxidation, while famotidine showed a biphasic concentration-dependent effect on spontaneous lipid peroxidation (a stimulation by 1 mM and an inhibition by 5 mM) and increased Fe(II)-induced- and inhibited Fe(II)/ascorbate-induced lipid peroxidation in the rat liver and brain. Both drugs decreased *OH-provoked deoxyribose degradation in Fenton-type systems and inhibited O2- -provoked reduction of nitro-blue tetrazolium and ferrycytochrome C, but famotidine effect was stronger than that of diphenhydramine. The significant famotidine-induced inhibition of nitro-blue tetrazolium reduction might be underlain by the stimulation of superoxide dismutase activity. Famotidine and diphenhydramine did not alter the catalase activity in all tissue preparations, except for its concentration of 5 mM (a complete inhibition). The present results suggest a beneficial effect of histamine H1 and H2-blockers, especially famotidine, as antioxidants and/or metal chelators, which might be an additional explanation of their therapeutic action.
Kesiova
Mila
M
Institute of Physiology, Bulgarian Academy of Sciences, Acad. G.Bonchev Str., Bild. 23, 1113 Sofia, Bulgaria.
Alexandrova
Albena
A
Yordanova
Neli
N
Kirkova
Margarita
M
Todorov
Simeon
S
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D004155:Diphenhydramine / Q000494:pharmacology*; D015738:Famotidine / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D000975:Antioxidants; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D017392:Thiobarbituric Acid Reactive Substances; D017665:Hydroxyl Radical; D015738:Famotidine; D004155:Diphenhydramine; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase