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

J Trace Elem Med Biol. 2023 Dec:80:127291. doi: 10.1016/j.jtemb.2023.127291. Epub 2023 Aug 26.

Abstract

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 MRC-5 and A 549 cancer cells. MRC-5 and A 549 cells exposed to Cd at 25 and 0.25 µM respectively, were treated with various non-toxic SL-L concentrations (2.5, 5, 10 µM) 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 µM and higher) exhibits pro-apoptotic features, lower concentrations (10 and 2.5 µM 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.

Keywords: Apoptosis; Cadmium; Lung cells; Silymarin liposome; Toxicity.

MeSH terms

  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Apoptosis
  • Cadmium / toxicity
  • Caspase 3 / metabolism
  • Humans
  • Lung / metabolism
  • Oxidative Stress
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Reactive Oxygen Species / metabolism
  • Silymarin* / pharmacology

Substances

  • Silymarin
  • Cadmium
  • Caspase 3
  • Reactive Oxygen Species
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Antioxidants