The Potential Protective Effects of Ginkgo Biloba on Bilirubin Cytotoxicity in Newborn Rat

Abstract

Objective: The mechanism of neurotoxicity associated with high serum bilirubin concentrations is still not fully elucidated. The cytotoxic effect of bilirubin has been demonstrated in various cell types, including astrocytes and neurons. The protective effect of Ginkgo biloba (EGB-761), which has antioxidant, anti-inflammatory, and anti-apoptotic effects, against neurotoxicity due to hyperbilirubinemia is not known. This study aimed to investigate the effect of EGB-761 in neonatal rat astrocyte cell cultures with hyperbilirubinemia-induced cytotoxicity. Methods: Astrocyte cell culture was obtained from one-day-old Wistar albino rats using the modified Cole and de Vellis method. Indirect bilirubin was found to be toxic to 50% of astrocyte cells at a dose of 10 µM (TC50). Bilirubin-induced apoptotic cell death was evaluated using the TUNEL staining method. EGB-761 increased cell viability by 100% and 110% at 10 µg/mL and 0.5 µg/mL concentrations, respectively. No drug was administered to the control group. In the study group, for the protective effect, 10 µM bilirubin was administered to the astrocyte cell culture 4 hours after 10 µg/mL EGB-761 was administered in the ginkgo10+bilirubin10 group, and for therapeutic effect, 10 µg/mL EGB-761 was administered 4 hours after 10 µM bilirubin was administered in the bilirubin10+ginkgo10 group, for a duration of 48 hours. Cell viability and apoptosis were evaluated in both prophylaxis and treatment groups after the procedure. Results: There was a 50% decrease in cell viability and a five-fold increase in apoptosis in the bilirubin10 group compared with the control group (p<0.001, p<0.001). EGB-761 given for prophylaxis and treatment increased cell viability (p<0.001, p<0.001) and reduce apoptosis (p<0.001, p<0.001) compared with the control group. Conclusion: In this in vitro study, it was shown that bilirubin has a cytotoxic effect on astrocyte cells, and EGB-761 used for prophylaxis and treatment reduced the cytotoxic effects of bilirubin. © 2022 by Medical Journal