ArticleActa pharmacologica Sinica2013
ROS generated by CYP450, especially CYP2E1, mediate mitochondrial dysfunction induced by tetrandrine in rat hepatocytes.
Article in Acta pharmacologica Sinica, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 58 citations in OpenAlex.
- Post-marketing safety assessment of tetrandrine based on the WHO-VigiAccess database.Medicine · 2026Article
- Mechanisms of postpartum metabolic dysfunction-associated steatotic liver disease in women with a history of gestational diabetes mellitus.Endocrine connections · 2026Review
- Reactive Oxygen Species Across Death Pathways: Gatekeepers of Apoptosis, Ferroptosis, Pyroptosis, Paraptosis, and Beyond.International journal of molecular sciences · 2025Review
- 4-Methylpyrazole-mediated inhibition of cytochrome P450 2E1 protects renal epithelial cells, but not bladder cancer cells, from cisplatin toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Oxidized Low-Density Lipoprotein as a Potential Target for Enhancing Immune Checkpoint Inhibitor Therapy in Microsatellite-Stable Colorectal Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- Tetrandrine induces muscle atrophy involving ROS-mediated inhibition of Akt and FoxO3.Molecular medicine (Cambridge, Mass.) · 2024Article
- Tetrandrine inhibits aldosterone synthesis by covalently targeting CYP11A1 to attenuate hypertension.Frontiers in pharmacology · 2024Article
- Mass spectrometry imaging as a promising analytical technique for herbal medicines: an updated review.Frontiers in pharmacology · 2024Review
- IL-6 Mutation Attenuates Liver Injury Caused byInternational journal of molecular sciences · 2023Article
- Hernandezine induces autophagic cell death in human pancreatic cancer cells via activation of the ROS/AMPK signaling pathway.Acta pharmacologica Sinica · 2023Article
- Synthesis, biological evaluation and toxicity of novel tetrandrine analogues.European journal of medicinal chemistry · 2020Article
- Higher sensitivity of female cells to ethanol: methylation of DNA lowers Cyp2e1, generating more ROS.Cell communication and signaling : CCS · 2020Article
- Autophagy mitigates ethanol-induced mitochondrial dysfunction and oxidative stress in esophageal keratinocytes.PloS one · 2020Article
- A critical review: traditional uses, phytochemistry, pharmacology and toxicology ofPhytochemistry reviews : proceedings of the Phytochemical Society of Europe · 2020Review
- Methionine Adenosyltransferase α1 Is Targeted to the Mitochondrial Matrix and Interacts with Cytochrome P450 2E1 to Lower Its Expression.Hepatology (Baltimore, Md.) · 2019Article
- Enhancing tetrandrine cytotoxicity in human lung carcinoma A549 cells by suppressing mitochondrial ATP production.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- Article
- Quantitative MALDI Imaging of Spatial Distributions and Dynamic Changes of Tetrandrine in Multiple Organs of Rats.Theranostics · 2019Article
- Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study.International journal of molecular sciences · 2018Review
- Effects of agmatine on chlorpromazine toxicity in the liver of Wistar rats: the possible role of oxidant/antioxidant imbalance.Experimental animals · 2017Article
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Authors and funding
5 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
aimTetrandrine, an alkaloid with a remarkable pharmacological profile, induces oxidative stress and mitochondrial dysfunction in hepatocytes; however, mitochondria are not the direct target of tetrandrine, which prompts us to elucidate the role of oxidative stress in tetrandrine-induced mitochondrial dysfunction and the sources of oxidative stress.
methodsRat primary hepatocytes were isolated by two-step collagenase perfusion. Mitochondrial function was evaluated by analyzing ATP content, mitochondrial membrane potential (MMP) and the mitochondrial permeability transition. The oxidative stress was evaluated by examining changes in the levels of reactive oxygen species (ROS) and glutathione (GSH).
resultsROS scavengers largely attenuated the cytotoxicity induced by tetrandrine in rat hepatocytes, indicating the important role of ROS in the hepatotoxicity of tetrandrine. Of the multiple ROS inhibitors that were tested, only inhibitors of CYP450 (SKF-525A and others) reduced the ROS levels and ameliorated the depletion of GSH. Mitochondrial function assays showed that the mitochondrial permeability transition (MPT) induced by tetrandrine was inhibited by SKF-525A and vitamin C (VC), both of which also rescued the depletion of ATP levels and the mitochondrial membrane potential. Upon inhibiting specific CYP450 isoforms, we observed that the inhibitors of CYP2D, CYP2C, and CYP2E1 attenuated the ATP depletion that occurred following tetrandrine exposure, whereas the inhibitors of CYP2D and CYP2E1 reduced the ROS induced by tetrandrine. Overexpression of CYP2E1 enhanced the tetrandrine-induced cytotoxicity.
conclusionWe demonstrated that CYP450 plays an important role in the mitochondrial dysfunction induced by the administration of tetrandrine. ROS generated by CYP450, especially CYP2E1, may contribute to the mitochondrial dysfunction induced by tetrandrine.
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