ABSTRACT
Phenylbutazone (PB), oxyphenbutazone (OPB), antipyrine (AP) and dipyrone (DP) are four important pyrazolone derivatives mainly used as anti-inflammatory, antipyretic and analgesic drugs. At present these are the most widely used pyrazolone derivatives throughout the world. The widespread use of these drugs are of great concern for human health problems. In the present study these four drugs were tested in mutagenicity assays in Salmonella strains TA97a, TA98, TA100 and TA102 using a plate incorporation assay both with and without S-9 mix and for in vivo sister chromatid exchanges (SCE) in bone marrow cells of mice. The first three drugs were negative in all the tester strains but dipyrone showed a weak mutagenic activity at higher concentrations in all four strains both with and without metabolic activation. In the in vivo SCE assay in male mice, all four drugs showed a statistically significant increase in SCE in bone marrow cells when compared with control.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/toxicity , Pyrazoles/toxicity , Pyrazolones , Salmonella/genetics , Sister Chromatid Exchange/genetics , Animals , Antipyrine/toxicity , Bone Marrow Cells/drug effects , Bone Marrow Cells/pathology , Dipyrone/toxicity , Liver/pathology , Male , Mice , Mutagenicity Tests , Oxyphenbutazone/toxicity , Phenylbutazone/toxicity , RatsSubject(s)
Carcinogens , Neoplasms/chemically induced , Acriflavine/analogs & derivatives , Acriflavine/toxicity , Animals , Anthralin/toxicity , Aurothioglucose/toxicity , Carcinogens/metabolism , Chloroquine/toxicity , Diazepam/toxicity , Ethanolamines/toxicity , Ethionamide/toxicity , Female , Humans , Hycanthone/toxicity , Male , Metronidazole/toxicity , Neoplasms, Experimental/chemically induced , Oxazepam/toxicity , Oxymetholone/toxicity , Oxyphenbutazone/toxicity , Oxyquinoline/toxicity , Phenacetin/toxicity , Phenobarbital/toxicity , Phenylbutazone/toxicity , Phenytoin/toxicity , Pregnancy , Pyrimethamine/toxicity , RiskABSTRACT
Cortical tubular necrosis induced by either aspirin (300 mg/kg) or oxyphenbutazone (444 mg/kg) was reduced if probenecid (300 mg/kg) was administered at the same time. The prior administration of aspirin (600 mg/kg) reduced the tubular necrosis that follows administration of oxyphenbutazone (444 mg/kg) alone, thus demonstrating that some degree of cross-tolerance between the two drugs occurs. Phenacetin pretreatment (597 mg/kg) was less effective, while paracetamol (503 mg/kg) was without effect in this regard. Those substances that reduced the oxyphenbutazone-induced cortical lesion also ameliorated the focal degenerative change in the lower nephron attributed to this drug. Oral administration of 2:4 dinitrophenol (20 mg/kg) led to only minor cortical tubular necrosis in a few animals.
Subject(s)
Acute Kidney Injury/chemically induced , Aspirin/toxicity , Dinitrophenols/toxicity , Kidney Tubular Necrosis, Acute/chemically induced , Oxyphenbutazone/toxicity , Acetaminophen/therapeutic use , Animals , Aspirin/therapeutic use , Female , Kidney Tubular Necrosis, Acute/prevention & control , Phenacetin/therapeutic use , Probenecid/therapeutic use , RatsABSTRACT
Experiments were donducted on rats to determine the lowest dose of either phenylbutazone or indomethacin capable of producing papillary necrosis and in each case it was found to be 50 mg/kg body weight. A single dose of oxyphenbutazone (444 mg/kg), a major metabolite of phenylbutazone in man, produced patchy cortical necrosis, which became more extensive during daily administration for 4 days, despite evidence of regeneration. Although papillary necrosis as such was never seen with this substance, there was evidence of damage to the lower nephron in the form of tubular necrosis and calcification.
