Biflavanone-kolaviron protects human dopaminergic SH-SY5Y cells against atrazine induced toxic insult

Atrazine (ATR) is a widespread agrochemical contaminant frequently detected in water systems and kolaviron (KV) is a seed-derived biflavonoid which is reported to modulate the effects of many mutagens and carcinogens. We investigated the protective effects of KV on ATR-induced cell death in the human neuroblastoma cell line (SHY-SY5Y). KV prevents ATR-induced generation of reactive oxygen species (ROS), cell death and inhibited cell proliferation by reduction of cell proliferation. Further, ATR-induced levels malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) activities, increased leakage of lactate dehydrogenase (LDH), inhibited cellular LDH activity and depleted glutathione (GSH) levels in SHY-SY5Y cells were blocked by KV. Comparable to the control, KV increased GR but not GSH-Px activities. ATR mediated nuclear changes associated with apoptosis; including nuclear fragmentation, condensation, DNA laddering, and increased caspase-3 activity were blocked on addition of KV. ATR-induced changes in the expressions of p53, Bax, Bcl-2, p21, and mRNA levels of caspase-3 and caspase-9 were prevented by KV. Based on these results, we propose a model for the protective effect of KV on ATR-induced cell injury in neuronal cell.