Resolvin D5 (RvD5) Reduces Renal Damage Caused by LPS Endotoxemia in Female Mice

Abstract

In self-revolving gram-negative Escherichia coli infection, Resolvin D5 (RvD5) was found to enhance bacteria phagocytosis and reduce the production of inflammatory mediators, contributing to the resolution of infection. LPS (lipopolysaccharide) is a gram-negative bacterial structure product which activates the immune system and, at high doses, leads to endotoxemia. To our knowledge, the effect of RvD5 against LPS endotoxemia has not been investigated to date. Female Swiss mice received an i.p. treatment with RvD5 (0.1, 1 or 10 ng/animal). After 1 h, they were stimulated with LPS (10 mg/kg, i.v.), and samples were collected after additional 6 h. The resulting data demonstrated that RvD5 protected the kidneys (urea and creatinine serum levels) from tissue injury. These effects were related to an improvement in histopathological parameters and a reduction of enzymatic markers of leukocyte infiltration, pro-inflammatory cytokine (IL-1β, TNF-α, and IL-6) production, and oxidative stress. Antioxidant markers were also increased by RvD5, but IL-10 (an anti-inflammatory cytokine) levels were unaltered. We also observed that RvD5 reduced the infiltration of CD45+ hematopoietic cells into the kidneys, reduced the activation of NFκB and promoted the Nrf2 pathway by reducing Keap-1 levels. Our data indicate that RvD5 may be a therapeutic possibility to reduce kidney lesions in LPS endotoxemia.

Is Lipid Metabolism of Value in Cancer Research and Treatment? Part II: Role of Specialized Pro-Resolving Mediators in Inflammation, Infections, and Cancer

“…In type 1 diabetes mellitus animal models, RvD5 decreased anxious-like and depression behaviors and decreased pro-inflammatory cytokine IL-1β in the hippocampus and prefrontal cortex [ 118 ]. In female mice, RvD5 reduced infiltration of CD45 + hematopoietic cells into the kidneys, reduced activation of NFκB, and promoted the Nrf2 pathway by reducing Kelch-like ECH-associated protein 1 levels [ 119 ]. The stereochemical assignment, total organic synthesis, and biological actions of each of the D-series Resolvins have been established [ 1 , 8 , 36 , 37 , 38 ], as reviewed in Table 1 .…”