Cytoprotective Effect of Silymarin on Moxifloxacin-Induced Liver Toxicity: Investigation of ER Stress (PERK/ATF6/GRP78), Oxidative Stress (Nrf2/HO-1) and Apoptosis (Caspase-3/Bax/Bcl-2) Pathways

Abstract This study aimed to evaluate the potential protective effect of silymarin (SLM) against the harmful effects of moxifloxacin (MXF) on liver tissue, utilising markers of oxidative stress, inflammation, apoptosis and endoplasmic reticulum (ER) stress. In the experimental study, rats were divided into five groups: control, SLM, MXF, MXF + SLM 25 and MXF + SLM 50. Applications were carried out for 7 days; liver tissues were examined histopathologically and the levels of molecular markers such as AST/ALT, MDA/GSH/GPx/SOD/CAT, Bax/Bcl-2/caspase-3, JAK2/STAT3, MAPK14/NF-Κb/TNF-α/IL-1β and PERK/ATF6/GRP78 were analyzed. In the MXF-administered group, notable liver tissue histopathological damage, a marked increase in oxidative stress, pro-inflammatory and pro-apoptotic markers, and a decrease in antioxidant and anti-apoptotic markers were observed. Additionally, increases in GRP78, PERK and ATF6 levels related to ER stress were observed. It was determined that these effects were significantly suppressed, liver histology was preserved, and molecular markers approached control levels in the groups in which SLM was applied together with MXF. The data collected revealed that silymarin showed a protective effect against moxifloxacin-induced liver toxicity, and this effect occurred by modulating oxidative stress, inflammation, apoptosis and ER stress responses. SLM can be considered a potential natural protective agent against drug toxicities. Graphical Abstract