Acute toxicity, 28-day repeated-dose toxicity and toxicokinetic study of timosaponin BII in rats
| Autor: | Bai-Ping Ma, Hongtao Jin, Bao-Feng Liu, Ni Lin, Yongpeng Long, Guo-Ming Dong, Jie Zhang |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Oral treatment medicine.medical_specialty Urinalysis Administration Oral Pharmacology Toxicology 01 natural sciences Neuroprotection Rats Sprague-Dawley 03 medical and health sciences Anemarrhena asphodeloides 0302 clinical medicine medicine Toxicity Tests Acute Toxicokinetics Animals Humans Anemarrhena No-Observed-Adverse-Effect Level medicine.diagnostic_test biology Dose-Response Relationship Drug Chemistry 010401 analytical chemistry Body Weight Toxicity Tests Subchronic General Medicine Saponins biology.organism_classification Acute toxicity 0104 chemical sciences Surgery Rats Neuroprotective Agents Toxicity Dementia Female Steroids 030217 neurology & neurosurgery Potential toxicity |
| Zdroj: | Regulatory toxicology and pharmacology : RTP. 90 |
| ISSN: | 1096-0295 |
| Popis: | Timosaponin BII (TBII), a major steroidal saponin isolated from Anemarrhena asphodeloides Bge., displays a variety of promising pharmacological activities, such as neuroprotection, enhancement of learning and memory, vascular protection and inhibition of platelet aggregation; therefore, it has been developed as a pharmaceutical for prevention or treatment of dementia. Given the safety concerns surrounding timosaponins and the absence of studies on the safety of TBII, the potential toxicity of TBII was evaluated in toxicity and toxicokinetic studies in rats. In the acute oral toxicity study, loose stools were observed in rats receiving 4000 mg/kg, and the symptoms recovered within 1 day. In the 28-day repeated-dose oral toxicity and toxicokinetic study, rats receiving 540 mg/kg showed loose stools and a slight deceleration of body weight growth in both sexes, and the females also showed a slight decrease in food consumption. Moreover, urinalysis indicated reversible treatment-related toxicity in rats receiving 540 mg/kg. The toxicokinetic study demonstrated a dose-dependent increase in systematic exposure to TBII after 28 successive days of oral treatment with TBII. The accumulation coefficients of TBII were 4.35, 1.70 and 1.81, respectively, in rats that received 60, 180 and 540 mg/kg. The no-observed-adverse-effect level (NOAEL) is proposed to be 180 mg/kg. |
| Databáze: | OpenAIRE |
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