Liposomal silymarin anti-oxidative and anti-apoptotic features in lung cells: An implication in cadmium toxicity

Background: Several metallic elements with high atomic weight and density are serious systemic toxicants, and their wide environmental distribution increase the risk of their exposure to human. Silymarin (SL), a polyphenol from milk thistle (Silybum marianum) plant has shown protective role against heavy metal toxicity. However, its low aqueous solubility and rapid metabolism limits its therapeutic potential in clinic.Methods: We compared the role of silymarin nanoliposomes (SL-L) against cadmium (Cd) toxicity in normal MRC5 and A 549 cancer cells. MRC-5 and A 549 cells exposed to Cd at 25 and 0.25 mu M respectively, were treated with various non-toxic SL-L concentrations (2.5, 5, 10 mu M) and cells viability, reactive oxygen species (ROS) generation, apoptosis and levels of cleaved PARP and caspase-3 proteins were determined following incubation.Results: Results indicated that Cd exposure significantly increased apoptosis due to ROS generation, and showed greater toxicity on cancer cells compared to normal cells. While SL-L at higher concentrations (25 mu M and higher) exhibits pro-apoptotic features, lower concentrations (10 and 2.5 mu M for MRC-5 and A 549 cancer cells, respectively) played a protective and anti-oxidant role in Cd induced toxicity in both cells. Further, lower SL-L was required to protect cancer cells against Cd toxicity. In general, treatment with SL-L significantly improved cell survival by decreasing ROS levels, cleaved PARP and caspase-3 in both MRC-5 and A 549 cells compared to free silymarin.Conclusion: Results demonstrated that SL-L potential in protecting against Cd-induced toxicity depends on concentration-dependent antioxidant and anti-apoptotic balance.