Assessment of Incessant Intake of Levonorgestrel Oral Contraceptive and the Effect of Drug Withdrawal on Liver Function and Integrity
Abstract
Objective: This study used female Wistar rats to evaluate the impact of incessant intake of levonorgestrel on liver function and integrity, and to observe the effect of drug withdrawal on the organs. (organ).
Material and Methods: Sixty rats (110–120g) were randomly placed in 3 groups (n=20). Group A was given the human dose equivalent of 1.83 mg/kg/bodyweight (BW) orally once weekly, Group B was given the same dose orally twice weekly, while Group C, serving as the control, was given the same dose of the vehicle solution. Rats were given food and water ad libitum. At the end of 30 days of treatment, 5 rats from each group were sacrificed by cervical dislocation, blood and the liver were harvested, weighed, and processed for biochemical and histological analyses. This was repeated at 60 and 90 days. The last batch of rats was left for another 30 days for possible recovery.
Results: The serum concentration of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (ƴGT), and total protein were significantly elevated in the serum. The histopathological examination showed hyperplastic degeneration and extensive tubular necrosis in the treated groups. After the drug was withdrawn, the altered levels of some of the determined biomarkers were not reversed.
Conclusion: This study showed a dose- and time-dependent toxicity of the liver, which was associated with levonorgestrel without improvement after drug withdrawal.
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