AI Article Synopsis
- Podophyllotoxin has potential clinical benefits, such as anticancer effects, but its toxicity limits its use in medicine.
- The research involved creating a rat model to study how podophyllotoxin damages ovaries, revealing symptoms like diarrhea and bruising, alongside significant biochemical and pathological changes.
- The study found that podophyllotoxin's toxicity is linked to alterations in autophagy, specifically through the AMPK/TSC1/mTOR/ULK1 signaling pathway, providing new insights for its clinical application.
Article Abstract
Background: Podophyllotoxin is a compound with clinical effects, such as anticancer and antiacromegaly effects, but its systemic toxicity has led to extremely limited clinical application.
Methods: Using the toxicological evidence chain (TEC) as a research method, our team constructed, for the first time, a rat model in which podophyllotoxin caused ovarian damage and investigated the mechanism of the toxic effects of podophyllotoxin on the ovaries.
Results: The rats presented different degrees of diarrhoea, body surface bruising, and petechiae, and the serum biochemical results revealed significant changes in the activities of the oxidative stress indicators SOD and MDA and the levels of the inflammatory indicators TNF-α and IL-1β. The pathological results suggested that the rat ovaries were significantly damaged, and the histological results revealed Th17 cell differentiation, necroptosis, Hspa9 expression, and other pathways or targets related to inflammation, necroptosis/apoptosis or autophagy.
Conclusion: Podophyllotoxin exerts toxic effects by altering autophagy through the AMPK/TSC1/mTOR/ULK1 signalling pathway. This study provides new insights into the mechanism of the toxic effects of podophyllotoxin and new ideas for the clinical application of podophyllotoxin.
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| http://dx.doi.org/10.1016/j.ecoenv.2024.117617 | DOI Listing |
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