Abstract

PRETREATMENT WITH GUM ACACIA SIGNIFICANTLY POTENTIATE THE CURING EFFECT OF DEXAMETHASONE AGAINST THE NEPHROTOXICITY INDUCED BY LIPOPOLYSACCHARIDE /DICLOFENAC COMBINATION IN RATS

Fawaz N. Alruwaili, Omnia A. Nour* and Tarek M. Ibrahim

ABSTRACT

Acute kidney injury (AKI) is a serious condition with high morbidity and mortality, often triggered by sepsis or drug-induced nephrotoxicity. Lipopolysaccharide (LPS), an endotoxin from gram-negative bacteria, and diclofenac (DIC), a widely used NSAID, contribute to AKI through oxidative stress, inflammation, and tubular cell damage. Gum acacia (GA), a natural dietary fiber with antioxidant properties, has shown potential renal protective effects. This study investigated the protective role of GA, alone and in combination with dexamethasone (DEX), against LPS/DIC-induced AKI in rats. Thirty-six male Sprague-Dawley rats were divided into six groups: control group, GA group, LPS/DIC group, GA+LPS/DIC group, DEX+LPS/DIC group, and GA+DEX+LPS/DIC group. Renal function, oxidative stress markers (MDA, GSH, TAC), inflammatory mediators (NF-κB, MAPK, iNOS), and antioxidant pathways (AMPK/Nrf2/HO-1) were assessed. LPS/DIC administration significantly increased serum creatinine, urea, proteinuria, and oxidative stress while reducing antioxidant defenses. GA and DEX treatment attenuated these effects, improving renal function, reducing oxidative damage, and suppressing inflammatory pathways. The combination of GA and DEX exhibited superior renoprotection, significantly enhancing AMPK and Nrf2 expression and reducing RAGE and COX-2 expression. The additive effect of GA and DEX highlights its potential as an adjunct therapy for AKI. Further studies are warranted to explore its clinical applicability.  

Keywords: Acute kidney injury, Lipopolysaccharide, Diclofenac, Gum acacia, Oxidative stress, AMPK/Nrf2 pathway.