Empagliflozin Exhibits Hepatoprotective Effects Against Bile Duct Ligation-induced Liver Injury in Rats: A Combined Molecular Docking Approach to In Vivo Studies

Abstract

Background: Cholestatic liver damage is a chronic disease caused by dysfunction of the hepatic-biliary system. Oxidative stress and inflammation are essential factors in the pathogenesis of cholestasis. Thus, the current study was designed to examine the effect of empagliflozin on bile duct ligation-induced liver damage in rats. Materials and methods: This study was done on male Wistar rats, which were randomly assigned to the four experimental groups: sham control (SC), bile duct ligation (BDL), SC plus empagliflozin (SC+EMPA) (Receive 10 mg of EMPA orally for 7 days), BDL plus empagliflozin 10 mg/kg (BDL+ EMPA). At the end of the study, the rats were sacrificed, and serum and tissue samples were collected to analyze biochemical parameters, biomarkers of oxidative stress, inflammatory markers, and histopathological changes. The molecular docking technique was performed to elucidate the interaction of EMPA and Cu/Zn-superoxide dismutase (SOD1). Results: The results showed that BDL elevated the serum activity of ALT, AST, ALP, and levels of TBIL and TPro. BDL also intensifies the oxidative stress state in rats, which was confirmed by augmenting lipid peroxidation (MDA), protein oxidation (PCO), and altering antioxidant defense parameters through decrease SOD, catalase (CAT), and glutathione peroxidase (GPX). Furthermore, the histopathological changes in the liver demonstrate the aggravation of inflammation and oxidative stress. In contrast, treatment with EMPA has shown anti-inflammatory and anti-oxidant effects by reducing TNF-a and IL-6 pro-inflammatory marker proteins, restoring the antioxidant status (increased SOD and GPX), reducing ALT, AST, ALP, TBIL, and protein oxidation, and improving the histopathological alterations through reducing bile duct proliferation, fibrosis, focal and portal inflammation. According to the attained findings, the SOD1 activity can be regulated by the EMPA. Our documentation presents direct evidence at the molecular level related to the ability of EMPA to exert its antioxidant performance through certain measures in a particular molecular route. Conclusions: The results showed EMPA had hepatic protective effects in rats against cholestatic liver injury, an effect mediated by its antioxidant and anti-inflammatory properties.

Empagliflozin impact on experimentally induced acetaminophen toxicity: Imprint of mitochondrial dynamics, biogenesis, and cGAS/STING signal in amending liver insult

“…A prolific deal of research validated the hepatoprotective effect of EMPA against drug‐induced hepatic injury 11,12 . Moreover, it has been acknowledged as beneficial in non‐alcoholic steatohepatitis and cholestatic liver injury 20,21 . However, its potential therapeutic imprint has still not been investigated in APAP‐induced ALI.…”

“…11,12 Moreover, it has been acknowledged as beneficial in non-alcoholic steatohepatitis and cholestatic liver injury. 20,21 However, its potential therapeutic imprint has still not been investigated in APAP-induced ALI. For progress, the present work sought to explore the pathomechanics beyond APAP-induced ALI and to particularly address the crucial role of mitochondrial dynamics, biogenesis, and the cGAS/STING signaling axis in pathology development.…”

Empagliflozin ameliorated chondrocytes inflammation, catabolism and senescence and osteoarthritis via suppressing the nuclear factor kappa-B signal pathway.

“…In recent years, Empa has been reported to regulate macrophage polarity and exert anti-inflammatory effects 10 . Also, Empa has hepatic protective effect against cholestatic liver injury via its anti-oxidant and antiinflammatory properties 11 . However, the effect of Empa on inflammation and senescence in OA has not been reported yet In our study, we hypothesized that Empa might inhibit inflammation in chondrocytes during the process of OA.…”