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Suppressive effects of thyroxine on glucocorticoid (gc)-induced metabolic changes and cataract formation on
H Kosano1, H Watanabe, H Nishigori
1Faculty of Pharmaceutical Sciences, Teikyo University, Sagami-ko, Kanagawa 199-0195, Japan. h-kosano@pharm.teikyo-u.ac.jp
Abstract:
To prevent cataracts induced by glucocorticoids (GC) as a systemic disease, the suppression of oxidative stress caused by GC in the hepatic metabolism is of significant interest. In this study, to elucidate the formative mechanism of GC-induced cataracts, we examined the preventive effect and then analysed the mechanisms of thyroxine on GC-induced cataract formation. Fifteen day old chick embryos were administered with 0.25 micromol hydrocortisone succinate sodium (HC), and then 12-30 nmol of thyroxine 4 hr after HC administration. At the indicated time after HC treatment, we examined the incidence of cataract formation, the levels of serum glucose and lipids, lenticular and hepatic glutathione (GSH), and lipid peroxide (LPO) in the lens, blood and liver. Almost all lenses (96%) removed 48 hr after HC administration were opaque. Thyroxine prevented HC-induced cataract formation effectively, and suppressed the elevations of serum glucose and LPO in the lens, blood and liver. The treatment prevented the decreased lenticular GSH level at 48 hr, but the hepatic GSH level at 24 hr remained lowered in contrast to the results of previous studies using insulin. Moreover, thyroxine did not decrease the elevated serum lipid level (triglyceride and non-esterified fatty acid) caused by HC. Under thyroxine treatment, in constant to insulin, acceleration of GSH-GSSG cycle rather than GSH de novo synthesis keeps a certain level of hepatic GSH necessary for diminishing the elevation of LPO as a risk factor of GC-induced cataract formation. The regulation of metabolic changes ensured the maintenance of hepatic GSH level, which is necessary to reduce oxidative stress produced by GC and to protect the lens from oxidative stress leading to opacification.
Insights
Thyroxine effectively prevents glucocorticoid-induced cataracts by suppressing oxidative stress and maintaining glutathione levels in chick embryos. This study highlights thyroxine
Area of Science:
- Biochemistry
- Endocrinology
- Ophthalmology
Background:
- Glucocorticoids (GC) can induce cataracts, a systemic condition linked to oxidative stress in hepatic metabolism.
- Understanding the mechanisms of GC-induced cataracts is crucial for developing preventive strategies.
Purpose of the Study:
- To investigate the preventive effects and underlying mechanisms of thyroxine on glucocorticoid-induced cataract formation.
- To elucidate how thyroxine modulates oxidative stress markers and metabolic changes associated with GC treatment.
Main Methods:
- Chick embryos were treated with hydrocortisone succinate sodium (HC) and subsequently with thyroxine.
- Evaluated cataract incidence, serum glucose and lipid levels, and glutathione (GSH) and lipid peroxide (LPO) levels in the lens, blood, and liver.
Main Results:
- Thyroxine significantly prevented HC-induced cataracts (96% opacity without treatment).
- Thyroxine suppressed elevated serum glucose and LPO, and prevented decreased lenticular GSH.
- Hepatic GSH levels remained lower at 24 hours, and thyroxine did not reduce elevated serum lipids.
Conclusions:
- Thyroxine effectively prevents GC-induced cataracts by mitigating oxidative stress and maintaining lens GSH levels.
- Thyroxine's mechanism involves accelerating the GSH-GSSG cycle to maintain hepatic GSH, crucial for reducing LPO and protecting the lens.
- Metabolic regulation by thyroxine is key to reducing GC-induced oxidative stress and preventing cataract formation.