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Severe hyperthyroidism induces mitochondria-mediated apoptosis in rat liver
Geeta Upadhyay1, Rajesh Singh, Ashok Kumar
1Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Hepatology (Baltimore, Md.)
|April 2, 2004
Summary
Excess thyroid hormone (thyrotoxicosis) causes liver dysfunction by triggering programmed cell death (apoptosis) in liver cells. This occurs through a pathway involving mitochondria, explaining observed hepatic abnormalities.
Area of Science:
- Hepatology
- Endocrinology
- Cell Biology
Background:
- Thyrotoxicosis is linked to liver dysfunction, but its cause is unclear.
- Mitochondrial dysfunction has been proposed as a mechanism for hepatic issues in thyrotoxicosis.
Purpose of the Study:
- To investigate the impact of altered thyroid function on liver cell apoptosis in rats.
- To elucidate the role of mitochondria in thyrotoxicosis-induced liver injury.
Main Methods:
- In vivo study of hyperthyroid rat livers assessing DNA fragmentation, caspase activity, and mitochondrial integrity.
- In vitro experiments involving isolated rat liver mitochondria treated with triiodothyronine (T3).
- Analysis of mitochondrial protein translocation (cytochrome c) and cell-free apoptosis assays.
Main Results:
- Hyperthyroid rat livers showed increased DNA fragmentation, caspase-3 and -9 activation, and apoptosis.
- Mitochondria in hyperthyroid livers exhibited outer membrane disruption and reduced cristae, with cytochrome c translocation.
- In vitro T3 treatment induced mitochondrial permeability transition and released apoptogenic proteins, causing nuclear changes and DNA fragmentation.
Conclusions:
- Excess thyroid hormone (T3) induces liver dysfunction via apoptosis mediated by a mitochondria-dependent pathway.
- This study provides evidence for the mechanism underlying hepatic dysfunction in thyrotoxicosis.
- The findings highlight the critical role of mitochondrial integrity in thyroid hormone-related liver injury.