Melatonin decreases bone marrow and lymphatic toxicity of adriamycin in mice bearing TLX5 lymphoma.
When CBA male mice bearing TLX5 lymphoma were treated in the evening with a single i.v. dose of adriamycin (20-40 mg/Kg), the administration of a single pharmacological dose of melatonin (10 mg/kg s.c.) 1 hr earlier reduced the acute mortality from 10/24 to 2/24. The increase in survival time caused by adriamycin over drug untreated controls was not reduced by melatonin. The administration of melatonin alone did not cause any antitumor or evident toxic effect. Melatonin also attenuated the reduction caused by adriamycin in the number of bone marrow GM-CFU, and of CD3+, CD4+ and CD8+ splenic T-lymphocyte subsets. Reduced and total glutathione levels were decreased in the bone marrow and in the liver cells of the animals treated with adriamycin, and were significantly restored by melatonin. Moreover, lipid peroxidation by adriamycin was reduced by melatonin, as indicated by malondialdehyde measurement in the liver of the treated animals. These data indicate that the protective effects of melatonin against the host toxicity of the prooxidant antitumor drug, adriamycin, might be attributed at least partially to its antioxidant properties. These findings appear of interest in relation to the physiological rhythmic levels of endogenous melatonin and to the chronotoxicology of anthracyclines.
Rapozzi
V
V
Department of Biomedical Sciences and Technologies, University of Udine, Italy.
Zorzet
S
S
Comelli
M
M
Mavelli
I
I
Perissin
L
L
Giraldi
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004317:Doxorubicin / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008206:Lymphatic Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008223:Lymphoma / Q000473:pathology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D004317:Doxorubicin; D005978:Glutathione; D008550:Melatonin