Empagliflozin Inhibits Cadmium-Induced Hepatic Cell Apoptosis Through Endoplasmic Reticulum Stress and Autophagy Pathways
Abstract
Cadmium (Cd), a well-known toxic heavy metal, adversely affects multiple organs. The SGLT-2 inhibitor empagliflozin (EMPA) exhibits significant antioxidant properties and hypoglycemic potential. This study aimed to investigate the hepatoprotective effect of EMPA against Cd-induced liver injury and elucidate its molecular mechanisms. Thirty-two male rats were allocated into four groups of eight rats each: group I (control group), group II (EMPA group), group III (Cd group), and group IV (Cd + EMPA group). Cd intake disrupted liver enzymes (ALT, AST, and ALP) and impaired hepatic histological architecture. Cd induced hepatic oxidative stress, as evidenced by increased MDA levels and reduced antioxidant enzymes, including SOD, GPx, and CAT. It downregulated the Nrf2/HO-1 pathway and elevated proinflammatory mediators IL-1β, IL-6, and TNF-α. Furthermore, Cd increased ER stress markers GRP78 and CHOP, along with apoptotic markers Bax and caspase-3 while decreasing anti-apoptotic Bcl-2 and reducing the autophagic indicator Beclin-1. Interestingly, EMPA administration in the Cd + EMPA group attenuated Cd-induced hepatic deterioration, improving hepatocyte structure. This beneficial effect was driven by the downregulation of hepatic oxidative stress, inflammation, ER stress, and apoptosis, alongside the upregulation of the autophagy process. In conclusion, this study highlights the hepatoprotective effect of EMPA against Cd-induced liver injury, elucidating its underlying molecular…
Read the paper
Related studies
- Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol
- Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance
- SGLT2 Inhibitors in Heart Failure: Targeted Metabolomics and Energetic Metabolism
- Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors
- Sodium-glucose cotransporter inhibitors: beyond glycaemic control
- Decoding the effects of SGLT2 inhibitors on cardiac arrhythmias in heart failure
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.