Toxicological evaluation of Oviductus ranae: Acute, sub-acute and genotoxicity studies in mice and rats.
BACKGROUND
Oviductus ranae (OR) is a traditional animal-based Chinese medicine, which has been listed in the Chinese Pharmacopoeia since 1985 edition. Although its medicinal application has been widely acknowledged, there is little available information on its potential toxicity.


OBJECTIVE
The aim of this study was to investigate the acute, sub-acute, and genetic toxicities of OR.


METHODS
In acute toxicity evaluation, OR was administered orally to mice at doses of 2.5, 5.0, 10.0, and 20.0g/kg BW for one time. Mortality, clinical signs, and body weight were observed for 14 days after treatment. In sub-acute toxicity evaluation, OR was administered orally to rats once a day for 28 consecutive days at doses of 1.75, 3.50, and 7.00g/kg BW. Animals were observed for general behaviors, mortality, food intake, and body weight changes. At the end of treatment, relative organ weight, pathology, hematological and biochemical parameters were monitored. In genotoxicity evaluation, bacterial reverse mutation assay (Ames test) was performed by treating OR with four different Salmonella typhimurium strains at doses of 8, 40, 200, 1000, and 5000μg/plate without or with S-9 mix, respectively. The genotoxicity of OR was also evaluated by micronucleus and sperm malformation assays in mice at doses of 2.5, 5.0, and 10.0g/kg BW, respectively.


RESULTS
The results of acute toxicity study showed that the LD50value of OR is higher than 20.0g/kg BW in mice. Death and abnormal clinical symptoms were not found during the period of experiment. In sub-acute toxicity, we found that the no-observed-adverse-effect levels (NOAEL) of OR in rats is up to 7.00g/kg BW. No statistically significant or toxicologically relevant defferences in body weight, food intake, relative organ weight, pathology, hematological and biochemical parameters were observed, when compared with control group. Results of Ames test, micronucleus and sperm malformation assays indicated that OR has no mutagenicity in vitro at a limited dose of 5000μg/plate, and dose not induce micronuclei and sperm malformation in mice at the dose of up to 10.0g/kg BW in mice.


CONCLUSIONS
In conclusion, OR is a tranditional Chinese medicine with high safety.
School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China; Engineering Research Center for Agricultural Resources and Comprehensive Utilization of Jilin Provence, Jilin Institute of Chemical Technology, Jilin 132022, China.
Yang
Y
Zhang
Department of Pharmacy, China-Japan Union Hospital of Jilin University, Changchun 130013, China.
Kun
K
Zhu
School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China; Engineering Research Center for Agricultural Resources and Comprehensive Utilization of Jilin Provence, Jilin Institute of Chemical Technology, Jilin 132022, China.
Hao
H
Cui
School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China.
Yang
Y
Liu
School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China.
Ye-Fang
YF
Lu
School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China.
Hong-Wei
HW
Pan
School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China.
He-Peng
HP
Zhao
College of Basic Medicine, Jilin Medical University, Jilin 132013, China.
Ling
L
Qi
School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China; Engineering Research Center for Agricultural Resources and Comprehensive Utilization of Jilin Provence, Jilin Institute of Chemical Technology, Jilin 132022, China.
Xiu-Dong
XD
Yang
School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China; Engineering Research Center for Agricultural Resources and Comprehensive Utilization of Jilin Provence, Jilin Institute of Chemical Technology, Jilin 132022, China. Electronic address: zhouhongli@jlict.edu.cn.
Hong-Li
HL
Zhou
D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D008419:Materia Medica / Q000008:administration & dosage / Q000633:toxicity*; D008516:Medicine, Chinese Traditional / Q000009:adverse effects*; D051379:Mice; D008813:Mice, Inbred ICR; D009152:Mutagenicity Tests; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D023382:Toxicity Tests, Acute; D059550:Toxicity Tests, Subchronic
D008419:Materia Medica; C539466:Oviductus Ranae
2-Aminofluorene (PubChem CID: 1539); Acute toxicity; Cyclophosphamide (PubChem CID: 2907); Dexon (PubChem CID: 23668198); Ethylenediaminetetraacetic acid (PubChem CID: 6049); Genotoxicity; Oviductus ranae; Pentobarbital sodium (PubChem CID: 23676152); Sodium azide (PubChem CID: 33557); Sub-acute toxicity