Abstract
We examined the effect of liposomalization on the changes of lipid peroxide level and glutathione peroxidase (GSHpx) activity in mice tissues after 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) administration. The agreement of the decrease in body weight on the 4th day after double MX2 administration (3.0mg/kg/day×2days, i.p.) was similar to those after adriamycin (ADR) administration (15mg/kg, i.p.). The lipid peroxide level in the heart and liver significantly increased after MX2 double treatment. GSHpx activity in the heart decreased to 80% on the 2nd day after MX2 injection, compared to normal activity. However, these changes are smaller than those after ADR administration (15mg/kg). NADPH-dependent microsomal lipid peroxidation in mouse liver increased, induced more by MX2 than by ADR. The combination of α-tocopherol with MX2 suppressed the increase in the lipid peroxide level by MX2 whereas did not suppress the decrease in GSHpx activity. Thus, it is considered that two mechanisms are involved, i.e., the increase in the lipid peroxide level occurs due to the production of active oxygen from MX2 and due to MX2-induced inhibition of GSHpx. The liposomalization of MX2 suppressed both MX2 induced changes in lipid peroxide level and GSHpx activity. Namely, it is considered that MX2 induced toxicity by these changes were reduced by α-tocopherol combination or liposomalization of MX2.
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