Prevention by fructose-1,6-bisphosphate of cardiac oxidative damage induced in mice by subchronic doxorubicin treatment.
An experimental model of mild, subchronic doxorubicin cardiotoxicity in mice was investigated by monitoring changes of biochemical parameters related to cell response against oxidative stress in both liver and heart. A specific increase of the lactate dehydrogenase isoenzyme typical of the heart was observed for doxorubicin-treated mice. Lipid peroxidation, as evaluated by malondialdehyde determination, and catalase activity were greatly increased in heart and unaffected in liver. On the other hand, these changes can be considered as indicative of early heart damage induced by doxorubicin. Glutathione, glutathione peroxidase, and 6-phosphogluconate dehydrogenase values were not significantly altered by the treatment and glucose-6-phosphate dehydrogenase increased in both liver and heart. Administration of fructose-1,6-bisphosphate strongly reduced the increase of plasma lactate dehydrogenase, heart lipid peroxidation, and heart catalase while no effect on the diagnostically irrelevant increase of glucose-6-phosphate dehydrogenase was observed. The inhibitory effect on the onset of biochemical modification typical of early subchronic doxorubicin cardiotoxicity may be related to stimulation of ATP synthesis by fructose-1,6-bisphosphate and is therapeutically promising in view of the lack of toxicity of fructose-1,6-bisphosphate as a drug.
Lazzarino
G
G
Biomedica Foscama Research Laboratories, Rome, Italy.
Viola
A R
AR
Mulieri
L
L
Rotilio
G
G
Mavelli
I
I
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D005635:Fructosediphosphates / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects*; D006598:Hexosediphosphates / Q000627:therapeutic use*; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D010084:Oxidation-Reduction
D000970:Antineoplastic Agents; D005635:Fructosediphosphates; D006598:Hexosediphosphates; D007527:Isoenzymes; D008054:Lipid Peroxides; D008315:Malondialdehyde; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D002374:Catalase; C029063:fructose-1,6-diphosphate