General and renal toxicity of phenacetin, paracetamol and some anti-mitotic agents in the rat
| Autor: | Nicole Baechtold-Fowler, F Chométy-Diézi, R Guidoux, Georges Peters, C Hedinger, J L Schelling, Lise Peters-Haefeli, Bernadette Filloux, J P Bonjour, Françoise Roch-Ramel, J.-P. Guignard, E Weber |
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| Rok vydání: | 1972 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Health Toxicology and Mutagenesis Urinary system Analgesic Growth Urine Pharmacology Kidney urologic and male genital diseases Toxicology Methemoglobinemia Nephrotoxicity Excretion Caffeine Internal medicine medicine Animals Urea Anilides Anemia Macrocytic Acetaminophen Mercaptopurine Chemistry Body Weight digestive oral and skin physiology Phenacetin Feeding Behavior General Medicine medicine.disease female genital diseases and pregnancy complications Diuresis Rats Blood medicine.anatomical_structure Endocrinology Depression Chemical Toxicity Glomerular Filtration Rate medicine.drug |
| Zdroj: | Archiv f�r Toxikologie. 28:225-269 |
| ISSN: | 1432-0738 0340-5761 |
| Popis: | The general and the renal toxicity of large doses of phenacetin, paracetamol, some antimitotic drugs and other constituents of analgesic mixtures was investigated in medium term toxicity tests in a large number of rats. Phenacetin and paracetamol depressed food intake and retarded growth. 800–1200 mg/kg · day paracetamol induced a larger mortality than 1500–3000 mg/kg · day phenacetin. Both analgesics and isophthalanilide, an antimitotic agent, induced hyperchromic anemia. Phenacetin induced methemoglobinemia more readily than paracetamol. Neither the analgesics, nor caffeine, sodium nitrite, isophthalanilide or mercaptopurine depressed GFR, maximal urinary concentration after dehydration plus vasopressin, urinary dilution after hypotonic expansion, or urinary acidification. Phenacetin, paracetamol and isophthalanilide depressed the fractional excretion of urea by the kidney. Very large doses of paracetamol slightly increased the proteinuria and the urinary excretion of tubular cells. Phenacetin and paracetamol induced degenerative histological alterations in cortical proximal and distal tubules, detected and quantitated under blind conditions. There were no inflammatory changes, nor any medullary or papillary lesions. The degenerative lesions could not be explained by the presence of methemoglobinemia or hemolysis. Isophthalanilide actually “improved” the histological appearance of the kidneys. The urinary excretion of tubular cells was not significantly correlated with the severity of the histological changes. It was concluded that neither phenacetin nor paracetamol exert major nephrotoxic effects in rats. |
| Databáze: | OpenAIRE |
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