Acute toxicity, 28-day repeated-dose toxicity and toxicokinetic study of timosaponin BII in rats |
| |
| Affiliation: | 1. Capital Medical University, Beijing 100069, People''s Republic of China;2. New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, People''s Republic of China;3. Shandong Xinbo Pharmaceutical R&D., Ltd., Shandong 251500, People''s Republic of China;4. Beijing Institute of Radiation Medicine, Beijing 100850, People''s Republic of China;5. Beijing Hwellso Pharmaceutical Corporation Ltd., Beijing 100081, People''s Republic of China;1. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China;2. XiaMen ZhongKe New Biotechnology Co., Ltd., Xiamen 361000, China;3. Department of Pharmaceuticals, PLA 102 Hospital, Changzhou, 213003 China;4. School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK;1. Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam, Gyeonggi 461-701, Republic of Korea;2. Department of Genetic Engineering, Sungkyunkwan University, Suwon, Gyeonggi 440-746, Republic of Korea;3. Department of Food and Nutrition, Chonnam National University, Gwangju, Republic of Korea;4. Department of Pharmacy, Sunchon National University, Suncheon, Jeonnam 530-742, Republic of Korea;5. Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-Do 426-791, Republic of Korea |
| |
| 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. |
| |
| Keywords: | Timosaponin BII Toxicity Toxicokinetics NOAEL Rats AD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0050" }," $$" :[{" #name" :" text" ," _" :" Alzheimer's disease ADME" },{" #name" :" keyword" ," $" :{" id" :" kwrd0060" }," $$" :[{" #name" :" text" ," _" :" absorption, distribution, metabolism, and excretion ADP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0070" }," $$" :[{" #name" :" text" ," _" :" adenosine diphosphate ALB" },{" #name" :" keyword" ," $" :{" id" :" kwrd0080" }," $$" :[{" #name" :" text" ," _" :" albumin ALP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0090" }," $$" :[{" #name" :" text" ," _" :" alkaline phosphatase ALT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0100" }," $$" :[{" #name" :" text" ," _" :" alanine aminotransferase APTT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0110" }," $$" :[{" #name" :" text" ," _" :" activated partial thromboplastin time AST" },{" #name" :" keyword" ," $" :{" id" :" kwrd0120" }," $$" :[{" #name" :" text" ," _" :" aspartate aminotransferase AUC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0130" }," $$" :[{" #name" :" text" ," _" :" area under concentration–time curve BASO" },{" #name" :" keyword" ," $" :{" id" :" kwrd0140" }," $$" :[{" #name" :" text" ," _" :" basophilic granulocyte BIL" },{" #name" :" keyword" ," $" :{" id" :" kwrd0150" }," $$" :[{" #name" :" text" ," _" :" bilirubin BLD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0160" }," $$" :[{" #name" :" text" ," _" :" blood BUN" },{" #name" :" keyword" ," $" :{" id" :" kwrd0170" }," $$" :[{" #name" :" text" ," _" :" blood urea nitrogen Ca" },{" #name" :" keyword" ," $" :{" id" :" kwrd0180" }," $$" :[{" #name" :" text" ," _" :" calcium ChEIs" },{" #name" :" keyword" ," $" :{" id" :" kwrd0190" }," $$" :[{" #name" :" text" ," _" :" cholinesterase inhibitors CHOL" },{" #name" :" keyword" ," $" :{" id" :" kwrd0200" }," $$" :[{" #name" :" text" ," _" :" total cholesterol CK" },{" #name" :" keyword" ," $" :{" id" :" kwrd0210" }," $$" :[{" #name" :" text" ," _" :" creatine kinase Cl" },{" #name" :" keyword" ," $" :{" id" :" kwrd0220" }," $$" :[{" #name" :" text" ," _" :" chlorine Clz/F" },{" #name" :" keyword" ," $" :{" id" :" kwrd0230" }," $$" :[{" #name" :" text" ," _" :" apparent clearance the maximum plasma concentration CPO" },{" #name" :" keyword" ," $" :{" id" :" kwrd0250" }," $$" :[{" #name" :" text" ," _" :" China Patent Office CREA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0260" }," $$" :[{" #name" :" text" ," _" :" creatinine DAS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0270" }," $$" :[{" #name" :" text" ," _" :" Drug and Statistic EOS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0280" }," $$" :[{" #name" :" text" ," _" :" eosnophils EPO" },{" #name" :" keyword" ," $" :{" id" :" kwrd0290" }," $$" :[{" #name" :" text" ," _" :" European Patent Office FDA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0300" }," $$" :[{" #name" :" text" ," _" :" Food and Drug Administration GC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0310" }," $$" :[{" #name" :" text" ," _" :" gas chromatography GLP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0320" }," $$" :[{" #name" :" text" ," _" :" Good Laboratory Practice GLU" },{" #name" :" keyword" ," $" :{" id" :" kwrd0330" }," $$" :[{" #name" :" text" ," _" :" blood glucose GLU" },{" #name" :" keyword" ," $" :{" id" :" kwrd0340" }," $$" :[{" #name" :" text" ," _" :" glucose HCT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0350" }," $$" :[{" #name" :" text" ," _" :" hematocrit HGB" },{" #name" :" keyword" ," $" :{" id" :" kwrd0360" }," $$" :[{" #name" :" text" ," _" :" hemoglobin IR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0370" }," $$" :[{" #name" :" text" ," _" :" infrared K" },{" #name" :" keyword" ," $" :{" id" :" kwrd0380" }," $$" :[{" #name" :" text" ," _" :" potassium KET" },{" #name" :" keyword" ," $" :{" id" :" kwrd0390" }," $$" :[{" #name" :" text" ," _" :" ketone LEU" },{" #name" :" keyword" ," $" :{" id" :" kwrd0400" }," $$" :[{" #name" :" text" ," _" :" leukocyte (urinalysis parameter) LYM" },{" #name" :" keyword" ," $" :{" id" :" kwrd0410" }," $$" :[{" #name" :" text" ," _" :" lymphocyte MCAO" },{" #name" :" keyword" ," $" :{" id" :" kwrd0420" }," $$" :[{" #name" :" text" ," _" :" middle cerebral artery occlusion MCH" },{" #name" :" keyword" ," $" :{" id" :" kwrd0430" }," $$" :[{" #name" :" text" ," _" :" mean corpuscular hemoglobin MCHC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0440" }," $$" :[{" #name" :" text" ," _" :" mean corpuscular hemoglobin concentration MCV" },{" #name" :" keyword" ," $" :{" id" :" kwrd0450" }," $$" :[{" #name" :" text" ," _" :" mean corpuscular volume MONO" },{" #name" :" keyword" ," $" :{" id" :" kwrd0460" }," $$" :[{" #name" :" text" ," _" :" monocyte MS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0470" }," $$" :[{" #name" :" text" ," _" :" mass spectroscopy MTD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0480" }," $$" :[{" #name" :" text" ," _" :" maximum tolerated dose Na" },{" #name" :" keyword" ," $" :{" id" :" kwrd0490" }," $$" :[{" #name" :" text" ," _" :" sodium nAChR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0500" }," $$" :[{" #name" :" text" ," _" :" nicotinic acetylcholine receptors NEU" },{" #name" :" keyword" ," $" :{" id" :" kwrd0510" }," $$" :[{" #name" :" text" ," _" :" neutrophilic granulocyte NIT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0520" }," $$" :[{" #name" :" text" ," _" :" nitrite NMDAR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0530" }," $$" :[{" #name" :" text" ," _" :" N-methyl-D-aspartate receptor NOAEL" },{" #name" :" keyword" ," $" :{" id" :" kwrd0540" }," $$" :[{" #name" :" text" ," _" :" no-observed-adverse-effect level P" },{" #name" :" keyword" ," $" :{" id" :" kwrd0550" }," $$" :[{" #name" :" text" ," _" :" phosphorus PDW" },{" #name" :" keyword" ," $" :{" id" :" kwrd0560" }," $$" :[{" #name" :" text" ," _" :" platelet distribution width pH" },{" #name" :" keyword" ," $" :{" id" :" kwrd0570" }," $$" :[{" #name" :" text" ," _" :" potential of hydrogen PLT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0580" }," $$" :[{" #name" :" text" ," _" :" platelets count PRO" },{" #name" :" keyword" ," $" :{" id" :" kwrd0590" }," $$" :[{" #name" :" text" ," _" :" protein PT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0600" }," $$" :[{" #name" :" text" ," _" :" prothrombin time RBC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0610" }," $$" :[{" #name" :" text" ," _" :" erythrocyte counts RDW" },{" #name" :" keyword" ," $" :{" id" :" kwrd0620" }," $$" :[{" #name" :" text" ," _" :" red cells distribution width-variation coefficient RETIC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0630" }," $$" :[{" #name" :" text" ," _" :" reticulocyte SG" },{" #name" :" keyword" ," $" :{" id" :" kwrd0640" }," $$" :[{" #name" :" text" ," _" :" specific gravity SPF" },{" #name" :" keyword" ," $" :{" id" :" kwrd0650" }," $$" :[{" #name" :" text" ," _" :" specific pathogen free elimination half-life TAIII" },{" #name" :" keyword" ," $" :{" id" :" kwrd0670" }," $$" :[{" #name" :" text" ," _" :" timosaponin AIII TBII" },{" #name" :" keyword" ," $" :{" id" :" kwrd0680" }," $$" :[{" #name" :" text" ," _" :" timosaponin BII TBIL" },{" #name" :" keyword" ," $" :{" id" :" kwrd0690" }," $$" :[{" #name" :" text" ," _" :" total bilirubin TG" },{" #name" :" keyword" ," $" :{" id" :" kwrd0700" }," $$" :[{" #name" :" text" ," _" :" triglyceride the corresponding time TP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0720" }," $$" :[{" #name" :" text" ," _" :" total protein UBG" },{" #name" :" keyword" ," $" :{" id" :" kwrd0730" }," $$" :[{" #name" :" text" ," _" :" urobilinogen USPTO" },{" #name" :" keyword" ," $" :{" id" :" kwrd0740" }," $$" :[{" #name" :" text" ," _" :" United States Patent and Trademark Office VC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0750" }," $$" :[{" #name" :" text" ," _" :" vitamin C VD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0760" }," $$" :[{" #name" :" text" ," _" :" vascular dementia Vz/F" },{" #name" :" keyword" ," $" :{" id" :" kwrd0770" }," $$" :[{" #name" :" text" ," _" :" volume of distribution WBC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0780" }," $$" :[{" #name" :" text" ," _" :" leukocyte (hematology parameter) |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
