A 13-WEEK DERMAL TOXICITY STUDY OF PREDNISOLONE FARNESYLATE (PNF) GEL IN RATS WITH A RECOVERY PERIOD OF 5 WEEKS
| Autor: | Shuzo Okazaki, Kazuhiro Anabuki, Eiichi Yamazaki, Toru Hoshiya, Hidetsugu Tanaka, Gotaro Tanaka, Kazutoshi Tamura |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Erythema Prednisolone Lymphocyte Administration Cutaneous Toxicology Rats Sprague-Dawley Internal medicine White blood cell medicine Animals Skin Hematologic Tests business.industry Body Weight Organ Size Farnesol Rats medicine.anatomical_structure Endocrinology Lymphatic system Liver Toxicity Female Bone marrow medicine.symptom business Gels Blood Chemical Analysis Glucocorticoid medicine.drug |
| Zdroj: | The Journal of Toxicological Sciences. 17:49-89 |
| ISSN: | 1880-3989 0388-1350 |
| DOI: | 10.2131/jts.17.supplementiii_49 |
| Popis: | The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF gel was administered dermally to the rats at doses of 0.25, 1, 4 and 16 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks to evaluate the reversibility. In addition, 10 mg/kg/day prednisolone gel (PN gel), which is approximate to 16 mg/kg/day PNF gel in prednisolone molarity, was also administered to the rats for comparison. The results are summarized as follows: 1. In the PNF gel 16 mg/kg/day group, temporary erythema at the application site, retarded body weight gains, a decrease in the white blood cell count and lymphocyte ratio with an increase in the segmented neutrophil ratio, an elevation of serum AIP activity were observed. The pathological examinations revealed atrophy of the adrenal glands, lymphatic organs and skin. In addition, histopathological lesions were also found in the liver, pancreatic islets, bone, bone marrow and mammary glands. 2. In the PNF gel 4 mg/kg/day group, retarded body weight gains were observed, and histopathological lesions were noted in the adrenal glands, lymphatic organs, skin at the application site, liver and bone marrows. 3. In the groups that received less than 1 mg/kg/day of PNF gel, there were no toxic signs induced by the drug. 4. In the PN gel 10 mg/kg/day group, drug-related changes were almost similar to those of the PNF gel group, but the severity of the lesions was stronger than in the PNF gel group. 5. After the 5-week recovery period, the above changes almost completely disappeared and so it was demonstrated that the changes were reversible. 6. Based on these results, it was concluded that the overt toxic dose of PNF gel was 4 mg/kg/day and the non-toxic dose was 1 mg/kg/day in the present study. |
| Databáze: | OpenAIRE |
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