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Acute toxicity, 28-day repeated-dose toxicity and toxicokinetic study of timosaponin BII in rats
- Source :
- Regulatory toxicology and pharmacology : RTP. 90
- Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 10960295
- Volume :
- 90
- Database :
- OpenAIRE
- Journal :
- Regulatory toxicology and pharmacology : RTP
- Accession number :
- edsair.doi.dedup.....cbe3464c43eb5bca121729e77149608b