Interactions of adriamycin with a calcium binding site

Canada, Robert G.; Saway, William; Thompson, Errol

doi:10.1016/s0006-291x(88)80334-6

Cited by 11 publications

(1 citation statement)

References 13 publications

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“…Phospholipids stimulate the formation of aldosterone from both corticosterone and 18-hydroxycorticosterone. Relative to our findings is that adriamycin not only interacts with phospholipid components of cells, but selectively inhibits several calmodulin-dependent reactions (37)(38)(39). In contrast to our studies performed in vivo, in isolated adrenocortical preparations adriamycin appears to inhibit 11/3-hydroxylase uncompetitively (40).…”

Section: Discussioncontrasting

confidence: 78%

Adriamycin-Induced Increase in Serum Aldosterone Levels: Effects in Riboflavin-Sufficient and Riboflavin-Deficient Rats*

et al. 1990

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Previous studies in rats have demonstrated that 1) aldosterone enhances biosynthesis of renal flavin coenzymes; 2) riboflavin analogs inhibit the synthesis of aldosterone; and 3) adriamycin inhibits flavin coenzyme biosynthesis. In their entirety, these findings suggest that both diminished flavin coenzyme biosynthesis induced by adriamycin and a dietary riboflavin deficiency would result in decreased formation of aldosterone. The present study examined the effects of adriamycin treatment on serum aldosterone in rats consuming either a diet adequate in riboflavin or a riboflavin-deficient diet. Groups of rats fed specially prepared diets were injected for 3 days with adriamycin (cumulative dose range, 6-24 mg/kg BW). Pair-fed controls were given saline. After death, adrenal glands were excised, and blood samples were analyzed for aldosterone levels. No changes in adrenal weights or protein and potassium concentrations were observed after adriamycin treatment. In contrast to initial predictions, in riboflavin-sufficient rats, serum aldosterone levels were markedly enhanced by adriamycin in a dose-related manner. Riboflavin-deficient animals had lower basal aldosterone levels and markedly attenuated responses to adriamycin than did riboflavin-sufficient rats. In separate groups of adriamycin-treated rats fed a normal chow diet, serum aldosterone levels increased, and serum corticosterone levels showed a small but significant decline. In addition, adriamycin treatment caused an increase in urinary potassium excretion and a decrease in sodium excretion. These results suggest that flavins play a decisive role in regulating the levels of aldosterone and raise the possibility that the adriamycin-induced increase in serum aldosterone may be part of the pathogenetic mechanisms of cardiovascular toxicity and overall muscular weakness.

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Section: Discussioncontrasting

confidence: 78%

Adriamycin-Induced Increase in Serum Aldosterone Levels: Effects in Riboflavin-Sufficient and Riboflavin-Deficient Rats*

et al. 1990

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Effects of adriamycin on chronic cardiotoxicity in selenium-deficient rats

et al. 1992

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Adriamycin (doxorubicin) is an antineoplastic drug used to treat various cancers; however, its chronic use is unfortunately accompanied by cardiotoxicity. This toxicity can be reduced by antioxidant agents such as selenium, and it is particularly interesting that cancer patients are usually deficient in this trace element, which suggests that its supplementation could contribute to beneficial treatment. We have examined the effect of adriamycin on chronic cardiotoxicity in 6-week selenium deficiency in rats. Selenium-deficient rats showed a considerable reduction of selenium levels and of selenium-containing glutathione peroxidase. Cardiac lipid peroxides increased slightly in the deficient rats, whereas plasma and heart lipid peroxides increased markedly in adriamycin-treated rats. This increase was greatly accentuated in selenium deficiency. These results suggest that free radical mechanism may be contributing to adriamycin toxicity, and above all show the importance of balancing the selenium levels in adriamycin-treated subjects to limit its harmful myocardial action. A decrease in adriamycin cardiotoxicity with no concomitant decrease in its antineoplastic activity would be of considerable value by improving the therapeutic benefit of the drug.

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Lipid peroxidation products, and vitamin and trace element status in patients with cancer before and after chemotherapy, including adriamycin

Faber

Coudray

Hida

et al. 1995

Biol Trace Elem Res

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Adriamycin is a potent chemotherapeutic agent used in the treatment of human neoplastic diseases. A major side effect limiting the use of this drug is its toxic effect on the heart. Several hypotheses have been proposed to explain the cardiotoxicity of Adriamycin. However, the most plausible hypothesis seems to be the reduction of Adriamycin and free radical production, which induces lipid peroxidation and oxidative damages in the heart. We have thus undertaken this preliminary study to investigate Adriamycin-induced lipid peroxidation by the measurement of plasma thiobarbituric acid reactant materials and antioxidant systems, namely glutathione content, glutathione peroxidase activity, and vitamin and trace element status, in patients with cancer before and after chemotherapy, including Adriamycin. The concentration of thiobarbituric acid reactant materials in plasma of patients with cancer was higher than in controls and was further increased after chemotherapy. Blood glutathione and plasma glutathione peroxidase activity, as well as plasma zinc and selenium in patients with cancer, were decreased, but not further modified by chemotherapy. However, only zinc and selenium levels reached a significant level. In contrast, plasma vitamin E and beta-carotene levels were not significantly increased in patients with cancer. Finally, plasma vitamin A and copper levels were not modified either in patients with cancer or by chemotherapy.

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Interactions of adriamycin with a calcium binding site

Cited by 11 publications

References 13 publications

Adriamycin-Induced Increase in Serum Aldosterone Levels: Effects in Riboflavin-Sufficient and Riboflavin-Deficient Rats*

Adriamycin-Induced Increase in Serum Aldosterone Levels: Effects in Riboflavin-Sufficient and Riboflavin-Deficient Rats*

Effects of adriamycin on chronic cardiotoxicity in selenium-deficient rats

Lipid peroxidation products, and vitamin and trace element status in patients with cancer before and after chemotherapy, including adriamycin

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