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Effect of adriamycin on DNA, RNA and protein biosyntheses in mouse tissues, in connection with its cardiotoxicity
Y Sazuka1, H Tanizawa, Y Takino
1School of Pharmaceutical Sciences, University of Shizuoka.
Abstract:
We examined whether the cause of the remarkable decreases in the activities of lipid peroxidation-preventive enzymes in the heart of adriamycin (ADR)-treated mice might be related to inhibition of DNA, RNA or protein biosynthesis. It was found that biosyntheses of DNA, RNA and protein in the heart, liver and kidney of mice were markedly inhibited by ADR (15 mg/kg, ip). The inhibitory effects of ADR on each type of biosynthesis were particularly marked in the heart among the tissues examined. Strong correlations between the percentage inhibition of DNA and protein biosynthesis by ADR, and the percentage decrease in the activities of lipid peroxidation-preventive enzymes were observed in the heart, liver, kidney and lung, especially for the decrease of glutathione peroxidase activity and the inhibition of DNA and protein biosyntheses. We also found that marked decreases of DNA, RNA and protein biosynthesis in ADR-treated mice occurred not only in the heart but also in tumor tissues. From these results, we conclude that the increment of cardiac lipid peroxide in ADR-treated mice, which is closely related to the cardiotoxicity of ADR, results from inhibition of DNA, RNA and protein biosyntheses after the distribution of ADR.
Insights
Adriamycin (ADR) significantly inhibits DNA, RNA, and protein synthesis in mouse hearts, leading to decreased protective enzymes. This biosynthesis inhibition is linked to ADR cardiotoxicity and increased cardiac lipid peroxide.
Area of Science:
- Biochemistry
- Pharmacology
- Cardiology
Background:
- Adriamycin (ADR) is an effective chemotherapeutic agent.
- ADR treatment is associated with significant cardiotoxicity.
- The mechanisms underlying ADR-induced cardiotoxicity are not fully understood.
Purpose of the Study:
- To investigate if decreased activities of lipid peroxidation-preventive enzymes in the heart of adriamycin-treated mice are linked to inhibited DNA, RNA, or protein biosynthesis.
- To explore the correlation between ADR-induced inhibition of biosynthesis and the reduction in enzyme activities.
- To determine if these inhibitory effects extend to other tissues, including tumor tissues.
Main Methods:
- Mice were treated with adriamycin (15 mg/kg, ip).
- Assessed the inhibition of DNA, RNA, and protein biosynthesis in heart, liver, kidney, and lung tissues.
- Measured the activities of lipid peroxidation-preventive enzymes, including glutathione peroxidase.
- Correlated the degree of biosynthesis inhibition with the decrease in enzyme activities.
Main Results:
- Adriamycin markedly inhibited DNA, RNA, and protein biosynthesis in the heart, liver, and kidney.
- The inhibitory effects were most pronounced in the heart.
- Strong correlations were observed between the inhibition of DNA and protein biosynthesis and the decrease in lipid peroxidation-preventive enzyme activities, particularly glutathione peroxidase.
- Inhibition of biosynthesis was also noted in tumor tissues.
Conclusions:
- Adriamycin-induced cardiotoxicity and increased cardiac lipid peroxide are likely caused by the inhibition of DNA, RNA, and protein biosynthesis.
- The observed decreases in lipid peroxidation-preventive enzymes are directly related to ADR's impact on cellular biosynthesis.
- These findings suggest a common mechanism of ADR toxicity across cardiac and tumor tissues.