Evaluation of the protective effect of cannabidiol against cadmium-induced toxicity in 2D and 3D model THLE-2 liver cell line

Abstract

Abstract The likelihood of human exposure to toxic metals is increasing due to various factors. Among these toxic metals, cadmium (Cd) holds a significant place. New methods and substances are needed to protect individuals against the harmful effects caused by Cd. In the Transformed Human Liver Epithelial-2 (THLE-2) cell line, the cytotoxic effect of Cd (IC50) was determined. To assess the protective efficacy of cannabidiol (CBD), some groups of cell lines were treated with Cd alone, while others were subjected to a combination of Cd and 5 µM CBD. GSH, MDA, MPO, CAT, TNF-α, IL-1β, and IL-6 levels in cell lines were determined using ELISA kits. The inhibition of toxic metal entry into the cells by CBD was evaluated through ICP-MS analysis. The IC50 value for Cd was determined as 5 µM in 2D cell lines and 10 µM in 3D cell lines. It was observed that the application of CBD at a concentration of 5 µM, along with the determined IC50 dose of Cd, increased the cell proliferation rate. Additionally, the decrease in GSH and CAT levels, and the increase in MDA, MPO, TNF-α, IL-1β, and IL-6 levels observed in cell lines treated only with Cd were reversed with the application of CBD. The ICP-MS analysis revealed that CBD reduced the uptake of Cd into the cells. CBD reverses the oxidative stress and inflammation caused by Cd, increases cell proliferation, and reduces Cd entry into the cell. This provides strong evidence for the protective role of CBD against Cd exposures.