Combined oral administration of ethinylestradiol and levonorgestrel alters the expression of antioxidant and apoptotic markers in female rats

Abstract

The use of ethinylestradiol and levonorgestrel (E/L) for birth control may result in serious adverse effects. Herein, the effect of (E/L) on the expression of genes encoding antioxidant enzymes (superoxide dismutase (SOD) and Catalase (CAT)), and apoptotic regulator genes (B-cell lymphoma 2 (BCL-2), caspase 1 and 3) was evaluated. Thirty-two rats were randomly divided into four equal groups. Group A (Control) received 0.5% DMSO, Group B, C and D received 0.015, 0.030, and 0.060 mg of E/L orally and daily for 21 days respectively. RNA extracted from brain, liver and kidney were purified, and the genes amplified using RT-PCR. Following analysis of the intensity of the amplicon bands on 1.2% agarose, the gene's relative expression compared with the expression β-actin was determined. There was significant downregulation of SOD and CAT genes in the liver, brain and kidney in all groups treated with E/L compared to control. Caspase 1 and 3 expressions were significantly elevated by 3.8 and 3.5 folds, respectively in the brain at the lowest E/L concentration. Expression of BCL-2 was downregulated in the brain and kidney in animals administered E/L at all concentrations. These findings suggest that E/L could modulate the expression of antioxidant and apoptosis marker genes.

Keywords: Ethinylestradiol, Levonorgestrel, Contraceptive, Antioxidant, Apoptosis