Exercise serum regulates uric acid transporters in normal rat kidney cells

Abstract

Hyperuricemia (HUA) refers to a physiological condition of high serum uric acid (SUA) level in the body, which may cause an increased risk of several chronic diseases. The kidney’s impaired uric acid (UA) metabolism is an important reason for HUA. In this study, we tested the hypothesis that circulating factors produced during exercise regulate the expression of ABCC4, ABCG2, URAT1, and GLUT9 in normal rat kidneys and normal rat kidney cells (NRK-52E) and their relationship with NF-κB and NRF-2. NRK-52E cells were separately cultured by serum from 10 healthy SD rats who did not exercise (CON) and 10 healthy SD rats who did aerobic treadmill exercise for 6 weeks. Cells cultured by serum from rats who did aerobic treadmill exercise for 6 weeks were separated by without NRF-2 inhibitor (EXE) and with NRF-2 inhibitor (EXE + ML). SUA level of rats was tested by using dry chemical assays, xanthine oxidase (XOD) activity in serum and liver were tested by using enzyme colorimetry assays, protein expression in kidney and NRK-52E cells were tested by using Western-blot, and UA levels in the upper or lower chamber were tested by colorimetry assays. Aerobic exercise reduced SUA levels in rats but did not significantly affect on liver xanthine oxidase. It also increased the expression of some UA transporters in the kidney and NRK-52E cells and increased the cells’ ability in UA excretion. When the NRF-2 was inhibited, the NF-κB and ABCG2 increased, and the expression of ABCC4, URAT1, and GLUT9 decreased. In conclusion, this study suggested that 6 weeks of aerobic treadmill exercise intervention may help to improve the excretion of UA in renal cells, suggesting that long-term aerobic exercise may be a means to prevent hyperuricemia.

High-Intensity Interval Training Ameliorates Tramadol-Induced Nephrotoxicity and Oxidative Stress in Experimental Rats

“…Although the precise mechanisms by which EXE affects renal indicators are not fully understood, researchers have demonstrated that increasing subjects' aerobic capacity reduces their reliance on phosphoryl compounds with high energy-producing capabilities during physical activity [ 35 ]. This adaptation is associated with decreased adenosine monophosphate deaminase activity and reduced uric acid production [ 36 ]. Additionally, EXE can enhance kidney function by increasing nitric oxide availability, reducing oxidative stress, and elevating antioxidant levels in kidney tissue [ 14 , 36 ].…”

“…This adaptation is associated with decreased adenosine monophosphate deaminase activity and reduced uric acid production [ 36 ]. Additionally, EXE can enhance kidney function by increasing nitric oxide availability, reducing oxidative stress, and elevating antioxidant levels in kidney tissue [ 14 , 36 ]. As a result, regular and continuous EXE adaptations can normalize blood urea, CR, and Alb levels.…”

Exploration of leech therapy in treating gouty rats and its uric acid lowering mechanism

“…In contrast, Yi-Suan-Cha increased UA excretion by increasing ABCG2 expression and synergistically reduce UA with a variety of transporter proteins in vivo [ 36 ]. Moreover, blood circulating factors in rats after prolonged exercise dramatically enhanced the capacity of renal tubular epithelial cells to reabsorb UA via GLUT9 [ 37 ], and Sanghuangporus vaninii ethanol extract (SHEE) lowered uric acid through increasing renal OAT3 mRNA expression in HUA-treated mice [ 38 ]. Leech therapy increase the expression levels of GLUT9, ABCG2, and OAT3 in the rat kidney to control uric acid metabolism in some extents.…”

High Intensity Interval Training (HIIT) Ameliorates the Tramadol-Induced Nephrotoxicity and Oxidative Stress in Experimental Rats

“…Lower blood urea levels indicate increased glomerular ltration and urea excretion through urine or decreased renal tubular reabsorption (52)(53)(54). Urea transport rate is determined by the electrochemical gradient for diffusion across the membrane and its permeability to the material (55). Furthermore, glomerular ltration depends on the negative charge of the podocyte basement membrane containing negatively charged molecules.…”