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Lipid peroxidation and its inhibition by tinoridine. I. Lipid peroxidation-induced disintegration of microsomal membrane and cytochrome P-450 in rat liver

1977; Elsevier BV; Volume: 489; Issue: 1 Linguagem: Inglês

10.1016/0005-2760(77)90242-9

1879-145X

Osafumi Shimada, Hiroshi Yasuda,

Eicosanoids and Hypertension Pharmacology

Incubation of rat liver microsomes with ascorbic acid resulted in the formation of malondialdehyde, the destruction of cytochrome P-450 and the decrease in the turbidity of the microsomal suspension. Tinoridine (2-amino-3-ethoxy-carbonyl-6-benzyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine), at the concentration of 5 μM, completely inhibited the peroxidative damages of microsomes. A similar inhibition by tinoridine was observed in NADPH-induced lipid peroxidation of microsomes. The anti-peroxidative activity of tinoridine was about 50 times greater than that of α-tocopherol. From the relationship between the concentration of tinoridine and the amount of malondialdehyde formed, it was demonstrated that 1 mol of tinoridine blocks the formation of about 10 mol of malondialdehyde. This suggests that lipid peroxidation proceeds as a chain reaction and that tinoridine inhibits the reaction at the initial step.