Nebivolol effect on oxidative biomarkers in Tamoxifen-Induced Hepatotoxicity in Female White Albino Rats: In Vivo Study
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Liver injury can arise post-exposure to drugs or their metabolites, as well as herbal and dietary supplements. Tamoxifen is a frequently used drug in breast cancer treatment. Unfortunately, Epidemiological studies have identified that Long-term tamoxifen treatment has been associated with the development of hepatotoxicity so it was used in this study to induce liver damage. Oxidative stress was the major implicated mechanism contributing to tamoxifen hepatotoxicity. Nebivolol is a third-generation selective beta1-adrenergic receptor blocker with vasodilator characteristics with significant antioxidant activity.
The presented study was conducted to investigate the possible protective role of nebivolol against rat hepatotoxicity induced by tamoxifen. Rats utilized in this study were randomized into five groups (6 in each group); Group 1- (Control) rats received distilled water (5mL/kg body weight orally) for 14 consecutive days. Group 2- Rats received distilled water for 12 consecutive days and tamoxifen (75mg/kg b.w., orally) on days 13 and 14 only. Group 3- Rats received Nebivolol (5 mg/kg b.w., orally for 14 consecutive days) and tamoxifen (75mg/kg b.w., orally) only on days 13 and 14. Group 4- Rats received Nebivolol (8 mg/kg b.w., orally for 14 consecutive days) and tamoxifen (75mg/kg b.w., orally) only on days 13 and 14. Group 5- Rats received Nebivolol (10 mg/kg b.w., orally for 14 consecutive days) and tamoxifen (75mg/kg b.w., orally) on days 13 and 14 only. The current study concluded that pre-administration of nebivolol with tamoxifen showed significant upregulation (P<0.05) in glutathione peroxidase (GPx) and significant downregulation (p<0.05) in malondialdehyde (MDA) each compared to corresponding levels in the tamoxifen-only treated group. In conclusion, this study demonstrated that pre-administration of nebivolol with tamoxifen attenuated its hepatotoxicity considering that nebivolol is a good choice, particularly for patients with hypertension requiring beta blockers and at risk for liver damage.
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