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.
Fatemeh Gheybi  1 ,  Fatemeh Rajabian  2 ,  Zahra Tayarani-Najaran  3 ,  Amir Reza Adibi  2 ,  Seyedeh Hoda Alavizadeh  4 ,  Prashant Kesharwani  5 ,  Amirhossein Sahebkar  6
Affiliations
  • 1. Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 2. Department of Pharmacodynamics and Toxicology, School of Pharmacy; Mashhad University of Medical Sciences, Mashhad, Iran.
  • 3. Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Toxicology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 4. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: [email protected].
  • 5. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India; Center for Global health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, India.
  • 6. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
PMID: 37672872 DOI: 10.1016/j.jtemb.2023.127291
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.
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