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 proce ss of various diseases. Using an animal model of diabetes (alloxan-induced hyperglycaemia in mice), a model of gastric ulcer (indomethacin-induced gas tric lesion in rats), and a model of bronchial asthma (ovalbumin-induced al lergic bronchospasm in guinea pigs), a potential therapeutic effect was tes ted in known antioxidant drugs (a-tocopherol, ubiquinone), the thio-compoun d mesna, and drugs with a possible antioxidant effect (substances derived f rom the ergoline structure: 6-hydroxynicotinic acid and 4-hydroxypyridine). The pre-treatment with ubiquinone and 6-hydroxynicotinic acid almost comple tely prevented alloxan-induced hyperglycaemia (94 and 93% inhibition of hyp erglycaemia, respectively). A weaker effect was shown by a-tocopherol and 4 -hydroxypyridine (31 and 27% inhibition of hyperglycaemia, respectively). M esna negligibly increased hyperglycaemia. 32% and 21% inhibitions of the nu mber of gastric lesions were shown after administration of 6-hydroxynicotin ic acid and a-tocopherol, respectively. Other drugs, most markedly mesna, a ggravated gastric lesions. The most marked protective effect on ovalbumin-i nduced bronchospasm was exerted by 6-hydroxynicotinic acid (the pulmonary v entilation was increased by 84% in comparison with control group), while me sna and (a-tocopherol had a weaker effect (amelioration by 50 and 51%, resp ectively). Ubiquinone and 4-hydroxypyridine aggravated pulmonary ventilatio n. The most marked protective effect in the animal models used was shown by 6- hydroxynicotinic acid.