Antiapoptotic effect of dipyrone on HL-60, Jurkat and Raji cell lines submitted to UV irradiation, arachidonic acid and cycloheximide treatments.
The effect of dipyrone (metamizol) on cell viability was evaluated in human leukocyte cell lines upon different apoptotic treatments: arachidonic acid (AA), cycloheximide (CHX), tumor necrosis factor (TNF) and ultraviolet (UV) irradiation. Dipyrone had a dual effect: at high concentrations (beyond 300 microM), it was cytotoxic, leading to apoptosis, whereas at lower concentrations (37.5-300 microM), it was cytoprotective, delaying the loss of membrane integrity triggered by arachidonic acid (100-200 microM) and UV irradiation and the cytotoxicity of cycloheximide (25-50 microM). No effect of dipyrone was found on TNF-induced cytotoxicity (250 ng/ml). The cytoprotective effect of dipyrone is associated with a decrease in DNA fragmentation, as assessed by electrophoresis of genomic DNA and by flow cytometry; a reduction in the percentage of condensed nuclei, as evaluated by DNA staining with Hoescht 33342 and a decrease in poly(ADP)-ribose polymerase (PARP) cleavage, as assessed by Western blotting. The cytoprotective effect of dipyrone on leukocyte apoptosis occurs at concentrations usually found for the main active metabolite of the drug and may have implications on the therapeutic and side effects caused by this agent.
Pompeia
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National Institute of Deafness and Other Communication Disorders, National Institutes of Health USA, Bethesda, MD 20892-4163. pompeiac@nidcd.nih.gov
Boaventura
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Curi
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D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000528:radiation effects; D003513:Cycloheximide / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004177:Dipyrone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects* / Q000528:radiation effects; D015448:Leukemia, B-Cell / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D010276:Parasympatholytics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014466:Ultraviolet Rays
D000700:Analgesics; D018712:Analgesics, Non-Narcotic; D016861:Cyclooxygenase Inhibitors; D009363:Neoplasm Proteins; D010276:Parasympatholytics; D011500:Protein Synthesis Inhibitors; D011837:Radiation-Protective Agents; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D004177:Dipyrone; D003513:Cycloheximide; D011065:Poly(ADP-ribose) Polymerases; D001241:Aspirin