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Aging-induced alterations in female rat colon smooth muscle: the protective effects of hormonal therapy
P Pascua1, C Camello-Almaraz, M J Pozo
1Department of Physiology, Nursing School, University of Extremadura, 10071 Caceres, Spain.
Abstract:
Aging is associated to oxidative damage and alterations in inflammatory and apoptotic pathways. Aging impairs secretion of several hormones, including melatonin and estrogens. However, the mechanisms involved in aging of smooth muscle are poorly known. We have studied the changes induced by aging in the colonic smooth muscle layer of female rats and the protective effect of hormonal therapy. We used young, aged, and ovariectomized aged female rats. Two groups of ovariectomized rats (22 months old) were treated either with melatonin or with estrogen for 10 weeks before sacrifice. Aging induced oxidative imbalance, evidenced by H(2)O(2) accumulation, lipid peroxidation, and decreased catalase activity. The oxidative damage was enhanced by ovariectomy. In addition, aged colonic muscle showed enhanced expression of the pro-inflammatory enzyme cyclooxygenase 2. Expression of the activated forms of caspases 3 and 9 was also enhanced in aged colon. Melatonin and estrogen treatment prevented the oxidative damage and the activation of caspases. In conclusion, aging of colonic smooth muscle induces oxidative imbalance and activation of apoptotic and pro-inflammatory pathways. Hormonal therapy has beneficial effects on the oxidative and apoptotic changes associated to aging in this model.
Insights
Aging causes oxidative damage and inflammation in colonic smooth muscle. Hormonal therapy with melatonin or estrogen protected against these age-related changes in female rats.
Area of Science:
- Gerontology
- Gastroenterology
- Cellular Biology
Background:
- Aging is linked to oxidative stress and inflammation, impacting hormone secretion like melatonin and estrogen.
- Mechanisms of smooth muscle aging, particularly in the colon, remain incompletely understood.
Purpose of the Study:
- To investigate aging-induced changes in colonic smooth muscle of female rats.
- To evaluate the protective effects of melatonin and estrogen therapy on aged colonic smooth muscle.
Main Methods:
- Comparative study using young, aged, and ovariectomized aged female rats.
- Hormonal therapy with melatonin or estrogen administered to ovariectomized aged rats for 10 weeks.
- Assessment of oxidative stress markers (H2O2, lipid peroxidation, catalase activity), inflammation (cyclooxygenase 2), and apoptosis (caspases 3 and 9).
Main Results:
- Aging induced significant oxidative imbalance, characterized by increased H2O2, lipid peroxidation, and reduced catalase activity.
- Ovariectomy exacerbated oxidative damage in aged colonic muscle.
- Enhanced expression of cyclooxygenase 2 and activated caspases 3 and 9 was observed in aged colonic smooth muscle.
- Melatonin and estrogen treatments effectively prevented oxidative damage and caspase activation.
Conclusions:
- Colonic smooth muscle aging is associated with oxidative imbalance and activation of pro-inflammatory and apoptotic pathways.
- Hormonal therapy, specifically with melatonin and estrogen, demonstrates beneficial effects in mitigating age-related oxidative and apoptotic changes in this rat model.
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