Regulatory Effects of Antioxidants on Indoxyl Sulfate-Enhanced Intracellular Oxidation and Impaired Phagocytic Activity in Differentiated U937 Human Macrophage Cells.

Indoxyl sulfate (IS), a uremic toxin, is a physiologically active sulfated metabolite, specifically in kidney failure patients. Our previous studies have shown that IS downregulates phagocytic immune function in a differentiated HL-60 human macrophage cell model. However, it remains unclear whether IS exerts similar effects on macrophage function in other cell types or in lipopolysaccharide (LPS)-sensitive immune cell models. Therefore, this study aimed to investigate the effects of IS on intracellular oxidation levels and phagocytic activity in a differentiated U937 human macrophage cell model, both in the absence and presence of LPS. Our results demonstrated that IS significantly increases intracellular oxidation levels and decreases phagocytic activity, particularly in cells activated by LPS. Furthermore, we found that 2-acetylphenothiazine, an NADH oxidase inhibitor, attenuates the effects of IS in LPS-activated macrophage cells. Representative antioxidants, trolox, α-tocopherol, and ascorbic acid, significantly mitigated the effects of IS on the macrophages responding to LPS.

Investigation and characterization of rat bipedal walking models established by a training program.

The purpose of the present study was to establish a rat bipedal walking model to examine the effects of bipedal walking on the central nervous system by training rats to perform bipedal walking over a period of 3 months. The characteristics of bipedal walking were investigated using kinematic and electromyographic methods in established bipedal walking models. Stable bipedal walking was achieved in rats by training them to stand with an upright posture and to walk with the hindlimbs using bipedal-walking training equipment to obtain a water reward. A stable head position in the rat bipedal walking model was attained primarily by closing the swing-phase period with a large angular change in the hip, knee, and ankle joints. The EMG burst pattern of the knee extensor (m. rectus femoris) and the erector muscle of the spine (m. longissimus) during bipedal walking was similar to that during quadrupedal walking in rats. We established two bipedal walking models using normal and forelimb-amputated rats. Comparative studies of these two bipedal walking models are expected to provide the information about the influence of forelimb movements on neuronal control of bipedal walking.