Protective Effect of Calcium Dobesilate on Induced AKI in Severely Burned Mice

Abstract

<b><i>Background:</i></b> Early acute kidney injury (AKI) predicts a high mortality rate in severely burned patients. However, the pathophysiology of early AKI induced by severe burn has not been well-defined. This study was designed to examine the protective effects of calcium dobesilate (CaD) against severe burn-induced early AKI in mice and explore the mechanism. <b><i>Methods:</i></b> The shaved backs of mice were immersed in 100°C water for 10 s to make severe burn (40% of the total body surface area). CD-57 male mice were randomly divided into sham, burn, burn + vehicle, and burn + CaD groups. Renal function, reactive oxygen species generation, tubular necrosis, and phosphorylation of mitogen-activated protein kinase, protein kinase B (Akt), and nuclear factor (NF)-κB were measured at 24 and 48 h after the burn. Renal histology, ELISA, qRT-PCR, and Western blotting were performed on the renal tissue of mice to examine the effects and mechanisms at 24 and 48 h after the burn. <b><i>Results:</i></b> Tubular damage, cast formation, and elevations of serum creatinine, BUN, and renal tissue kidney injury molecule 1 levels were all observed in the burned mice, and these were all alleviated in the mice with CaD treatment. In addition, the levels of oxidation-reduction potential and malondialdehyde were decreased, while the activities of the endogenous antioxidative enzymes were increased in the kidney tissues from the mice after CaD treatment. Furthermore, the activities of Akt, p38, extracellular sign-regulated kinase, Jun N-terminal kinase, and NF-κB signaling were increased in the kidney of burned mice and normalized after CaD treatment. <b><i>Conclusion:</i></b> This study has established, for the first time, the protective effect of CaD against early AKI in severely burned mice. CaD may exert its protective effect through alleviating oxidative stress, apoptosis, and inflammation, as well as modulating some signaling pathways in the kidney.