Short chain fatty acid, acetate ameliorates sepsis-induced acute kidney injury by inhibition of NADPH oxidase signaling in T cells.

Sepsis affects millions of people worldwide and is associated with acute kidney injury (AKI). Innate and adaptive immune cells have been shown to play an important role in AKI through release of various inflammatory mediators which include reactive oxidant species (ROS). Acetate, a short chain fatty acid produced by gut bacteria has anti-inflammatory properties and has also been shown to modulate oxidative stress in different immune cells. Effects of acetate have been shown to be both GPR43 dependent and independent in different cells/tissues. However, the role of acetate on T cell NADPH oxidase (NOX2)/ROS signaling remains unexplored during sepsis-induced AKI. Therefore, the current study investigated the effect of acetate on sepsis-induced AKI parameters and T cell oxidant-antioxidant balance. Our results show that acetate ameliorates sepsis-induced AKI as reflected by a decrease in serum, creatinine/blood urea nitrogen and renal myeloperoxidase activity/lipid peroxides and restoration of kidney tubular structure. Moreover, acetate administration was associated with correction of oxidant-antioxidant imbalance in T cells during sepsis-induced AKI. Acetate produced its inhibitory effects on NOX2/ROS signaling via attenuation of histone deacetylase activity in T cells which was induced during AKI. Overall, the data suggest that acetate might be beneficial during sepsis-induced AKI by restoration of oxidant-antioxidant balance in T cells.