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["Dose-time-toxicity" relationship study on hepatotoxicity caused by multiple dose water extraction components of
Wei Huang1, Xiaojiaoyang Li, Rong Sun
1Shandong Research Academy of Traditional Chinese Medicine, Ji'nan 250014, China.
Objective:
To study on the time-toxicity and dose-toxicity relationships caused by multiple dose water extraction components of Evodia Fructus to mice.
Method:
Mice were grouped according to different time or dose points, to observe the death condition and toxicity of mice. The changes of the activity of ALT, AST and liver, kidney index were detected, and the morphological changes of liver tissue were observed under light microscope.
Result:
On the first day after administration the hepatotoxicity which displayed with obvious increase of ALT, AST activity in serum and liver tissue and hepatic injury appeared. On the third day the hepatotoxicity kept a higher level that the active units in serum ALT, AST were significantly higher than the normal group. On the 7th day after administration ALT, AST level in serum are restored near normality. Compared with the normal group, within 7 days after the administration, water extracted components in 0.63-5.0 g x kg(-1) dose scope could cause significant damage to liver, the activity of ALT, AST, AKP, TBI elevated, while ALB reduced, and liver ratio increased, and under light microscope, the different doses' liver tissue of mice all had different degree's edema, fatty degeneration in liver cells and interstitial congestion. There were certain time-toxicity and dose-toxicity relationships. The above-mentioned change gradually aggravated with dose increasing, and it was the obvious discrepancy compared with distilled water control group.
Conclusion:
Multiple intragastric administrations of water extracted components of Evodia Fructus with certain dosage may induce acute hepatotoxical injury in mice and show certain "dosage-time-toxicity" relationship.
Insights
Evodia Fructus water extract components caused liver injury in mice, with toxicity increasing with dose and time. This study establishes a clear dosage-time-toxicity relationship for Evodia Fructus hepatotoxicity.
Area of Science:
- Pharmacology
- Toxicology
- Natural Products
Context:
- Evodia Fructus is a traditional medicinal herb.
- Understanding its toxicological profile is crucial for safe use.
- Water extraction is a common method for preparing herbal medicines.
Purpose:
- To investigate the dose-toxicity and time-toxicity relationships of Evodia Fructus water extract components in mice.
- To assess the acute hepatotoxicity induced by Evodia Fructus.
- To establish the "dosage-time-toxicity" relationship.
Summary:
- Mice administered Evodia Fructus water extract showed increased serum ALT, AST, and AKP, decreased ALB, and elevated liver index.
- Hepatotoxicity, including liver tissue edema and fatty degeneration, was observed.
- Toxicity levels correlated with both the dosage and duration of administration, demonstrating a clear dose-time-toxicity relationship.
Impact:
- Provides crucial toxicological data for Evodia Fructus.
- Informs safe dosage recommendations for Evodia Fructus preparations.
- Highlights the potential for acute hepatotoxicity with certain dosages and administration times.
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