Multiple organ toxicity, including hypochromic anemia, following repeated dose oral administration of phenobarbital (PB) in rats
| Autor: | Akiko Enomoto, Junya Sasaki, Hisao Kawakatsu, Tadashi Kosaka, Machiko Saka, Toshinori Yoshida, Katsumi Ishizuka, Sayuri Kojima, Nobuaki Nakashima, Mariko Tomita, Takanori Harada |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Iron Cmax Administration Oral Urinalysis Hematocrit Toxicology Eating Oral administration Internal medicine Toxicity Tests medicine Animals Platelet activation Gait Anemia Hypochromic medicine.diagnostic_test Transferrin saturation Chemistry Body Weight Organ Size medicine.disease Rats Inbred F344 Rats Hypochromic anemia Endocrinology Liver Phenobarbital Immunology Toxicity Female Hemoglobin |
| Zdroj: | The Journal of Toxicological Sciences. 34:527-539 |
| ISSN: | 1880-3989 0388-1350 |
| DOI: | 10.2131/jts.34.527 |
| Popis: | A 4-week repeated dose oral toxicity study of phenobarbital (PB) sodium was conducted in F344 rats of both sexes at PB doses of 0.8, 8, and 80 mg/kg/day to fully elucidate its general toxicity including hematological changes. Both sexes in the 80 mg/kg/day group showed staggering gait, lacrimation, and/or sedation, which were more evident in the early stage of treatment. The body weight gain and food consumption were greater in these animals than in controls. Hematology revealed a significant reduction in the hematocrit (Ht), hemoglobin concentration (Hb), and erythrocyte count (RBC) in both sexes at 80 mg/kg/day, which was accompanied by a decrease in the cell mean Hb (CHCM) in mature erythrocytes with an increase in unsaturated iron binding capacity. Female rats also showed reduction in the CHCM in reticulocytes, content of hemoglobin per reticulocyte, and transferrin saturation. PB prolonged the activated partial thromboplastin time and inversely increased the platelet count with no evidence of platelet activation. Well-known toxic effects of PB on the liver and thyroid were observed in a dose-dependent manner, along with altered lipid, glucose, and electrolyte metabolism. The serum levels of PB increased dose-dependently, when examined in females received 8 and 80 mg/kg/day on day 1 and 28; there were no difference in C(max) and AUC(0-24) values between day 1 and day 28. These results indicated that PB has the potential to elicit multiple organ toxicity including an effect on the hematopoietic system. The hematological analysis provided evidence for hypochromic anemia, plausibly caused by the impairment of iron utility. |
| Databáze: | OpenAIRE |
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