Related Experiment Videos
Assessment of Xiao'er Xiexieting Keli-induced toxicity in juvenile rats
Junxiu Liu1, Lin Zhu2, Xiaojing Lu2
1Key Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, 310053, China.
Insights
Xiao'er Xiexieting Keli (XXTK), a pediatric diarrhea herbal formula, showed a favorable safety profile in juvenile rat toxicity studies. Findings support its potential clinical use in children, warranting further pediatric validation.
Area of Science:
- Pharmacology
- Toxicology
- Pediatric Medicine
Background:
- Limited safety data exists for Xiao'er Xiexieting Keli (XXTK), a Chinese herbal formula used for pediatric diarrhea.
- Assessing the safety of XXTK in juvenile populations is crucial for its clinical application.
Purpose of the Study:
- To evaluate the toxicity of XXTK in juvenile rats.
- To establish a safety and dosage basis for XXTK in pediatric use.
Main Methods:
- Acute toxicity study in postnatal day (PND) 24 rats with a single oral dose of 253.13 g/kg XXTK.
- Subacute toxicity study in PND21 rats with daily oral administration of 1.74, 8.71, or 32.66 g/kg XXTK for six weeks, followed by a four-week recovery period.
- Comprehensive assessments including clinical signs, body weight, food intake, developmental milestones, hematology, serum biochemistry, histopathology, and behavioral tests.
Main Results:
- The maximum tolerated dose in the acute study was 253.13 g/kg.
- In the subacute study, all observed changes were mild, reversible, and without toxicological significance.
- The no-observed-adverse-effect level (NOAEL) was determined to be 32.66 g/kg/day.
Conclusions:
- XXTK exhibits a favorable toxicological safety profile in juvenile rats.
- The findings support the potential for XXTK's extended clinical use in children.
- Further research on child development indicators and pediatric clinical validation is recommended.
Ethnopharmacological Relevance:
Sufficient safety data on juvenile development is not available for Xiao'er Xiexieting Keli (XXTK), a Chinese herbal formula for pediatric diarrhea.
Aim Of The Study:
Considering the challenges associated with clinical trials of XXTK, this study was aimed at evaluating its toxicity in juvenile rats to obtain a basis for assessing its safety and dosage in children.
Materials And Methods:
In acute toxicity study (Study 1), postnatal day (PND) 24 rats were orally administered 253.13 g/kg XXTK and observed over 14 days. In subacute toxicity study (Study 2), PND21 rats were administered 1.74, 8.71, or 32.66 g/kg XXTK daily for six consecutive weeks and allowed to recover for 4 weeks. Clinical signs, body weight, food intake, and timing of vaginal opening and preputial separation were recorded during the dosing period. Hematological, serum biochemical, and histopathological examinations, Irwin's test, and assessment of growth hormone levels, skeletal development, and immune-related indicators were performed mid-administration, and at culmination of dosing and recovery. Urinalysis, ophthalmological assessment, and Morris water maze test were conducted at the end of dosing and recovery periods.
Results:
No deaths or significant findings occurred in Study 1; maximum tolerated dose was 253.13 g/kg. In Study 2, all changes were reversible, mild, and without toxicological significance. The no-observed-adverse-effect level was 32.66 g/kg/day.
Conclusion:
XXTK demonstrated a favorable toxicological safety profile in juvenile rats, supporting its potential for extended clinical use in children. Further evaluation of child development-related indicators and validation in pediatric clinical cohorts are recommended.
