Effects of known and potential antioxidants on animal models of pathological processes (diabetes, gastric lesions, allergic bronchospasm).
Highly reactive oxygen-free radicals are implicated in the pathogenic process of various diseases. Using an animal model of diabetes (alloxan-induced hyperglycaemia in mice), a model of gastric ulcer (indomethacin-induced gastric lesion in rats), and a model of bronchial asthma (ovalbumin-induced allergic bronchospasm in guinea pigs), a potential therapeutic effect was tested in known antioxidant drugs (alpha-tocopherol, ubiquinone), the thio-compound mesna, and drugs with a possible antioxidant effect (substances derived from the ergoline structure: 6-hydroxynicotinic acid and 4-hydroxypyridine). The pre-treatment with ubiquinone and 6-hydroxynicotinic acid almost completely prevented alloxan-induced hyperglycaemia (94 and 93% inhibition of hyperglycaemia, respectively). A weaker effect was shown by alpha-tocopherol and 4-hydroxypyridine (31 and 27% inhibition of hyperglycaemia, respectively). Mesna negligibly increased hyperglycaemia. 32% and 21% inhibitions of the number of gastric lesions were shown after administration of 6-hydroxynicotinic acid and alpha-tocopherol, respectively. Other drugs, most markedly mesna, aggravated gastric lesions. The most marked protective effect on ovalbumin-induced bronchospasm was exerted by 6-hydroxynicotinic acid (the pulmonary ventilation was increased by 84% in comparison with control group), while mesna and (alpha-tocopherol had a weaker effect (amelioration by 50 and 51 %, respectively). Ubiquinone and 4-hydroxypyridine aggravated pulmonary ventilation. The most marked protective effect in the animal models used was shown by 6-hydroxynicotinic acid.
Stetinová
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Institute of Experimental Biopharmaceutics, Joint Laboratories of the Academy of Sciences of the Czech Republic Hradec Králové. stetinova@uebf.cas.cz
Grossmann
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V
D000496:Alloxan; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001986:Bronchial Spasm / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006168:Guinea Pigs; D017665:Hydroxyl Radical; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D017665:Hydroxyl Radical; D000496:Alloxan; D007213:Indomethacin