Determination of the effects of syringic acid against cadmium-induced oxidative stress, ER stress, inflammation and apoptosis in kidney tissue of rats by in silico and in vivo methods

Cadmium (Cd) is a toxic heavy metal that causes kidney damage and poses a significant risk to living things with its various harmful effects. This study aims to alleviate Cd-induced kidney damage in rats by utilizing the various therapeutic effects of syringic acid. Five groups of 7 rats were formed: Control and SA 100 groups were cadmiumfree, while the Cd group received 6.5 mg/kg intraperitoneal (IP) CdCl2. SA 50 + Cd and SA 100 + Cd received daily SA (50 mg/kg and 100 mg/kg, respectively) via intragastric gavage. SA treatment reduced the production of Cd-induced proinflammatory mediators TNF-alpha, IL-1 beta, NF-kappa B, and TLR4 in kidney tissues and reduced Cdinduced histopathological changes. SA reduced the increased MDA content after Cd administration, while increasing the decreased SOD and GSH levels. Moreover, SA significantly inhibited the expression of Keap1, while increasing the expression of Nrf-2 and HO-1. The results of this study also indicate that SA regulates Cdinduced ER stress (by reducing GRP78, ATF4, ATF6 and CHOP protein expression), apoptosis (by reducing caspase-3 and Bax, and increasing Bcl-2 expression). This study demonstrates that SA suppresses Cd-induced oxidative damage, ER stress, and activation of inflammatory pathways, and has the potential to be used therapeutically in kidney injury.