The Prophylactic and Therapeutic Effects of Safranal and Selenite on Liver Damage Induced by Thyrotoxicosis in Adult Male Rats

Abstract

Aim: To evaluate the prophylactic and therapeutic activities of safranal and selenite against liver damage induced by thyrotoxicosis. Materials and Methods: Thyrotoxicosis was induced by thyroxine (L-T4, 500 µg/kg, s.c.). Safranal (50 mg/kg, i.p.) or selenite (0.25 mg/kg, oral) was administered either with or after thyroxine. All treatments continued daily over three weeks. Results: Treatment of rats with L-T4 resulted in significant elevations in fT3 and fT4 levels and significant reductions in the serum TSH level and body weight confirming the establishment of thyrotoxicosis. Thyrotoxicosis resulted in significant elevations in serum ALT and AST activities and hepatic levels of malondialdehyde and nitric oxide in addition to significant reductions in hepatic GSH level and the activities of catalase and SOD indicating the oxidative insult and depletion of antioxidants. Thyrotoxicosis also caused significant upregulations in the mRNA expression of bax, bax/bcl-2 ratio, and caspase-9 and a significant downregulation of bcl-2 in liver but did not affect the caspase-3 expression which would collectively induce apoptosis. Consequently, the DNA fragmentation was also increased and severe histopathological appearance of liver was reported. Safranal and selenite were able to mitigate all the previous injurious effects of thyrotoxicosis through bolstering the antioxidant defense systems. Conclusions: The alleviation offered by safranal was better than that shown after selenite administration. Treating the hyperthyroid animals with safranal or selenite gave better palliating results than those reported for the protection regimen.