Therapeutic effect of berberine against 5-fluorouracil induced ovarian toxicity in rats

Berberine (BER) is a naturally occurring alkaloid with a multitude of beneficial effects on human health. Although it is one of the most studied phytochemicals, its curative effect against ovarian damage caused by 5-fluorouracil (5-FU) has not been demonstrated to date. The aim of this study was to investigate the possible protective effect of BER against 5-FU-induced ovotoxicity, focusing on its ability to attenuate oxidative stress, inflammation and apoptosis. The 30 female rats were randomly divided into five groups: Control, BER (2 mg/kg), 5-FU (100 mg/kg), 5-FU+BER (1 mg/kg) and 5-FU+BER (2 mg/kg). The levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT), 8-hydroxy-2'-deoxyguanosine (8-OHdG), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and caspase-3 were determined using spectrophotometric methods. In addition, ovarian samples were evaluated histopathologically using hematoxylin&eosin staining method. The MDA, TOS, 8-OHdG, IL-6, TNF-α and caspase-3 levels significantly increased by 5-FU administration. Also, we found that 5-FU significantly decreased TAS, SOD and CAT levels. Treatments with BER significantly attenuated the 5-FU-induced ovarian damage via increasing the antioxidant capacity and reducing the oxidative stress, inflammation and apoptosis in a dose-dependent manner. Moreover, the ovoprotective effect of BER was also confirmed by histopathological evaluation. BER may be evaluated as a potential candidate molecule to reduce 5-FU-induced ovarian toxicity.