#4561 VOLUNTARY EXERCISE EXACERBATES CHRONIC KIDNEY DISEASE INDUCED BY FOLIC ACID IN MALE C57BL6J MICE

Abstract

Abstract Background and Aims Voluntary exercise is of utmost importance to avert a plethora of diseases and to ameliorate other conditions, such as neuromuscular diseases, however in some occasions, the inflammation can be exacerbated by intense physical activity. The folic acid kidney disease model is of key interest since it is non-invasive and leads to conspicuous fibrosis. Our main objective was to determine the influence of voluntary exercise on chronic kidney disease in folic acid-treated mice. Method Male C57/Bl6 mice were divided into 3 groups, vehicle (V), folic acid (FA), and folic acid + voluntary exercise (FA + E). The animals were kept in cages with or without voluntary wheels (sedentary or exercised groups) for 30 days, and then received a single injection of folic (240 mg/kg i.p.) in 0.3 mol/L sodium bicarbonate. The animals were euthanized after 28 days. Results Chronic kidney disease in the folic acid model is exacerbated by voluntary exercise. Voluntary exercise decreases the survival level in animals treated with folic acid (V- 100%, FA- 85,71%, FA+ E- 60%). On day 28 after folic acid administration the urea levels (FA vs. FA + E P= 0,003) and creatinine (V vs. FA + E p= 0,0004; FA vs. Fa+ E p= 0,0001). Renal injury marker such as KIM-1 (FA vs. FA + Ex p= 0,0131, FA vs. Fa+ E p= 0,0213) was higher in animals that went to the wheel, but NGAL showed no significant differences. Inflammation markers as IL-6 (V vs. FA + Ex p= 0,0337 FA vs. Fa+ E p= 0,0254) and TLR4 (V vs. FA + Ex p= <0,0001 FA vs. Fa+ E p= <0,0001) were exacerbated as well as apoptosis relation BAX/BCL2 (V vs. FA + Ex p= <0,0001 FA vs. Fa+ E p= <0,0001). Picrosirius red staining was used to assess tubulointerstitial fibrosis and the kidney architecture; animals from the FA+E group showed the highest destruction of kidney architecture. Conclusion We established that previous voluntary exercise has deleterious effects on nephrotoxic folic acid–Induced CKD.