Evaluation of the Differential Effect of Female Sex Hormones on Hepatic Inflammatory and Apoptotic Markers in a Model of Acute Systemic Inflammation in the Female Rats

Document Type : Original Article

Authors

1 Department of Physiology, Faculty of Medicine, Cairo University

2 Department of Medical Biochemistry, Faculty of Medicine, Cairo University

Abstract

The present study was conducted to investigat the differential effect of estradiol benzoate and progesterone on systemic as well as the liver response to experimentally induced inflammatory states. Materials and Methods: The study was conducted on 48 female albino rats divided into six groups. Groups I and II consisted of non-ovariectomized animals. Ovariectomy was performed for the remaining 4 groups which were allocated randomly to receive one form of the following daily hormonal supplementation: Subcutaneous (SC) Estradiol benzoate 4μg/100g body weight (BW) , or SC progesterone 5mg/kg BW or; combined daily estradiol and progesterone supplementation or no hormonal supplement at all. At the end of three weeks period, acute systemic inflammation was induced by caecal ligation and puncture in all the groups except group I and the animals were sacrificed 24 hours later and both serum and liver tissue were isolated to evaluate inflammatory and apoptotic markers. Results: Ovariectomized animals subjected to systemic inflammation had significantly higher levels of serum Tumor necrosis factor alpha (TNFα), C reactive protein and Alanine Aminotransferease (ALT). They also had higher levels of expression of the enzyme inducible nitric oxide sysnthetase (iNOS) in the liver, and of the activity of both cycloxygenase II (COXII) and Caspase 3 enzymes when compared to non- ovariectomized animals subjected to systemic inflammation. Daily supplementation of ovariectomized animals with estradiol resulted in a significant reduction of all serum and liver tissue parameters of inflammation and apoptosis when compared to ovariectomized animals with systemic inflammation receiving no supplementary treatment. In contrast, daily supplementation of ovariectomized animals with progesterone resulted in a significant rise of all measured parameters of serum and liver tissue inflammation and apoptosis when compared to their corresponding values in ovariectomized animals with systemic inflammation and receiving no supplementary treatment. Conclusion: Estradiol supplementation that achieves physiological pro-estrus to diestrus levels in ovariectomized animals can reduce the excessive harmful effects of inflammation and apoptois on the systemic and liver tissue level while progesterone supplementation that achieves estrus physiological levels increases the release of inflammatory mediators and liver tissue apoptosis.

Keywords

Bulletin of Egyptian Society for Physiological Sciences
Volume 29, Issue 2
December 2009
Pages 15-32

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