Evaluation of the protective effects of histamine and 5-hydroxytryptamine receptor antagonists against the lethal toxicity induced by oxygen free radicals in rats.
Generation of oxygen free radicals (OFR) via intravenous administration of xanthine plus xanthine oxidase [X + XO], to Inactin(R) anesthetized rats produced intense respiratory distress. This effect led to death of more than 90% of the animals within a 120 min observation period. Several reports documented that the two autocoids, 5-hydroxytryptamine (5-HT) and histamine (H), can induce pulmonary and bronchiolar constriction and pulmonary edema. Hence, our present studies were conducted to investigate whether antagonists of 5-HT and histamine could provide protection from the lethal toxicity of the free radicals. Pretreatment of the rats with pyrilamine and cimetidine, H1 and H2 receptor antagonists, respectively, prolonged the duration of survival, but it failed to enhance net survival rate. In contrast, pretreatment of the rats with nonspecific 5-HT antagonists, methysergide and cyproheptadine, and a selective 5-HT(2) receptor antagonist, ketanserin, markedly enhanced the survival rate to 80-90%. These observations are consistent with data showing that 5-HT levels in the systemic arterial blood doubled within 5-10 min after administration of [X + XO]. These studies support the view that OFR-mediated respiratory distress is caused predominantly by 5-hydroxytryptamine and to a lesser extent by histamine.
Heart and Kidney Institute, College of Pharmacy, University of Houston, Texas 77204-5041, USA.
Mayur S
MS
Tripathi
Bhagavan S
BS
Jandhyala
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006633:Histamine Antagonists / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000633:toxicity; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
D006633:Histamine Antagonists; D017382:Reactive Oxygen Species; D012702:Serotonin Antagonists