Dose-Dependent Renal Tubular Toxicity of Harman and Norharman in Male F344 Rats
| العنوان: | Dose-Dependent Renal Tubular Toxicity of Harman and Norharman in Male F344 Rats |
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| المؤلفون: | Nobuyuki Ito, Akihiro Hagiwara, Masao Hirose, Emiko Asakawa, Yasushi Kurata, Masashi Sano |
| المصدر: | Toxicologic Pathology. 20:197-204 |
| بيانات النشر: | SAGE Publications, 1992. |
| سنة النشر: | 1992 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Brush border, 040301 veterinary sciences, Urinary system, Drinking, Urination, Urine, Toxicology, 030226 pharmacology & pharmacy, Acetylglucosamine, Pathology and Forensic Medicine, 0403 veterinary science, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Phagocytosis, Oral administration, Lactate dehydrogenase, Internal medicine, medicine, Animals, Molecular Biology, Kidney, L-Lactate Dehydrogenase, Microvilli, DNA, Organ Size, 04 agricultural and veterinary sciences, Cell Biology, Rats, Inbred F344, Rats, Harmine, Kidney Tubules, Endocrinology, medicine.anatomical_structure, Bromodeoxyuridine, chemistry, Toxicity, Alkaline phosphatase, Kidney Diseases, Carbolines |
| الوصف: | The renal toxicity of harman and norharman, administered for 2 or 4 weeks at dietary levels of 1,000, 500, or 0 parts per million (ppm), was investigated in 6-week-old male F344/DuCrj rats. Although rats fed 1,000 ppm harman or norharman, but not the 500 ppm level, demonstrated marked body weight retardation from 1 week to termination, no mortalities occurred. Marked elevation of water consumption was evident in rats given harman or norharman at 1,000 ppm, but not at 500 ppm, together with large increases in urine of low specific gravity. Urinary lysosomal enzymes ( N-acetyl-βT-D-glucosaminidase, NAG, and lactate dehydrogenase, LDH) and sugar levels were increased, and the brush border enzymes (γ-glutamyl transpeptidase, GGT, and alkaline phosphatase, ALP) decreased. Furthermore, serum biochemistry revealed clear elevation of parameters indicating renal toxicity in these rats. Histopathologically, rats fed 1,000 ppm harman or norharman, but not 500 ppm, demonstrated focal toxic renal degenerative/necrotic and regenerative lesions in proximal, distal, and collecting tubules. These changes were associated with a clearly increased labeling index (LI) of the nuclei of renal tubular epithelial cells on immunohistochemical staining for 5-bromo-2′-deoxyuridine (BrdU). Chemical specific crystal formation within tubular lumina was evident in rats fed 1,000 ppm, but not 500 ppm, this being considered the cause of the renal tubular lesions. It was concluded that harman and norharman exert renal toxicity at the dietary level of 1,000 ppm, but not 500 ppm, in male F344 rats. |
| تدمد: | 1533-1601 0192-6233 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c2a36fee3b9f5a86c5db261f54f2ec24Test https://doi.org/10.1177/019262339202000206Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c2a36fee3b9f5a86c5db261f54f2ec24 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15331601 01926233 |
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