Semicarbazide protection from in vivo oxidant injury of vascular tissue by allylamine.
Allylamine is a specific cardiovascular toxin that causes vascular and myocardial lesions. Previous studies showed that allylamine-induced chronic lesions are markedly reduced by semicarbazide, an inhibitor of semicarbazide-sensitive amine oxidase (SSAO), and that allylamine is metabolized to the aldehyde, acrolein, by SSAO. We hypothesized that inhibitors of SSAO might reduce the acute cardiovascular toxicity of allylamine. To test our hypothesis, we fed 150 mg/kg allylamine to semicarbazide-pretreated (3 h; 98 mg/kg) rats. Animals were sacrificed 1 h after allylamine treatment. Aorta, epicardium, and endocardium were assayed for SSAO, glutathione peroxidase, catalase, thiol status and lipid peroxidation. SSAO activity was decreased significantly in aorta, epicardium and endocardium. Activity was 30-times higher in aorta than in epicardium and endocardium. A striking decrease in malonaldehyde level (lipid peroxidation) was found in aorta of pretreated rats as compared to allylamine-only treated rats. The reduction of free-SH content in aortic mitochondria was also attenuated in pretreated rats. Changes were not so marked in epicardium and endocardium. These results suggest that in vivo pretreatment with semicarbazide at least partially protects aortic mitochondria from allylamine toxicity. The mechanism can be explained on the basis of the fact that semicarbazide inhibits acrolein formation in allylamine-treated rats.
Awasthi
S
S
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0605.
Boor
P J
PJ
D000499:Allylamine / Q000633:toxicity*; D006631:Amine Oxidase (Copper-Containing); D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012663:Semicarbazides / Q000494:pharmacology*
D012663:Semicarbazides; C010059:carbamylhydrazine; D000499:Allylamine; D008315:Malondialdehyde; D006631:Amine Oxidase (Copper-Containing); D000587:Oxidoreductases Acting on CH-NH Group Donors