Abstract
Background: Chronic kidney disease is a global health problem for which renal fibrogenesis is the final treatment target.
Objective: In our work, we have highlighted two new strategies, nicorandil and Bone marrow-derived mesenchymal stem cells (BM-MSCs), as effective in reversing renal fibrosis induced by partial unilateral ureteral obstruction (PUUO).
Methods: The current study included 96 male albino rats randomly divided into four groups, with 24 rats per group; Group I, the control group; Group II, PUUO, where two-thirds of the left ureter was entrenched in the psoas muscle; Group III, same surgical procedure as in Group II for 7 days, and then the rats received 15 mg/kg/day nicorandil once daily for 21 days; and Group IV, same surgical procedure as in Group II for 7 days, and then rats were given 3 × 106 of labeled MSCs injected intravenous, and left for 21 days. Blood and kidney tissues were collected for biochemical, histological, and molecular analyses.
Results: Both the nicorandil and BM-MSCs treatment groups could ameliorate kidney damage evidenced by inhibition of MDA elevation and total antioxidant capacity reduction caused by PUUO. Also, there was a significant reduction observed in TNF, TGF, IL6, collagen I, and α-SMA in addition to improvement in histological examination. However, a significant difference was found between the BM-MSCs and nicorandil-treated groups.
Conclusion: Our results suggest that BM-MSCs and nicorandil improved renal fibrosis progression through their antiapoptotic, anti-inflammatory, and antifibrotic effects in male albino rats subjected to PUUO, with BM-MSCs being more effective compared to nicorandil.
Keywords: BM-MSCs, nicrorandil, renal fibrosis, ureteral obstruction, TNF, α-SMA.
Graphical Abstract
[http://dx.doi.org/10.1111/nep.12380] [PMID: 25516387]
[http://dx.doi.org/10.1007/s00383-013-3456-8] [PMID: 24370792]
[http://dx.doi.org/10.1371/journal.pone.0158765] [PMID: 27383068]
[http://dx.doi.org/10.1097/01.EHX.0000508456.99217.6e]
[http://dx.doi.org/10.1016/j.biopha.2018.02.090] [PMID: 29518614]
[http://dx.doi.org/10.1097/00005344-200006000-00014] [PMID: 10836727]
[http://dx.doi.org/10.1212/WNL.0b013e3182a35228] [PMID: 23911756]
[http://dx.doi.org/10.1016/j.ejphar.2011.04.038] [PMID: 21549700]
[http://dx.doi.org/10.1016/j.kjms.2017.03.003] [PMID: 28433070]
[http://dx.doi.org/10.3892/ijmm.14.6.1035] [PMID: 15547670]
[http://dx.doi.org/10.1038/nprot.2008.221] [PMID: 19131962]
[http://dx.doi.org/10.1016/j.mam.2018.06.002] [PMID: 29909119]
[http://dx.doi.org/10.1053/j.ajkd.2012.07.005] [PMID: 23067652]
[http://dx.doi.org/10.1007/s11427-018-9334-2] [PMID: 30099707]
[http://dx.doi.org/10.1016/j.stem.2017.07.011] [PMID: 28777943]
[http://dx.doi.org/10.1002/9781444345148.ch7]
[PMID: 19339234]
[http://dx.doi.org/10.1089/end.2009.0035] [PMID: 19530942]
[http://dx.doi.org/10.1046/j.1523-1755.2001.00724.x] [PMID: 11380811]
[http://dx.doi.org/10.1007/s10157-014-0998-6] [PMID: 24952900]
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.06.009] [PMID: 18625301]
[http://dx.doi.org/10.1016/j.clim.2008.08.016] [PMID: 18922742]
[http://dx.doi.org/10.1016/j.jss.2010.06.022] [PMID: 20850784]
[http://dx.doi.org/10.3892/mmr.2018.8848] [PMID: 29620281]
[http://dx.doi.org/10.1172/JCI200319270] [PMID: 14617750]
[http://dx.doi.org/10.1089/scd.2008.0092] [PMID: 18564903]
[http://dx.doi.org/10.1016/j.arcmed.2016.03.002] [PMID: 27018336]
[http://dx.doi.org/10.1210/en.2010-0286] [PMID: 20826562]
[http://dx.doi.org/10.1371/journal.pone.0090883] [PMID: 24646687]
[http://dx.doi.org/10.1254/jphs.09072FP] [PMID: 19721333]
[http://dx.doi.org/10.1155/2017/6894040]
[PMID: 23818365]
[http://dx.doi.org/10.3892/ijmm.2013.1232] [PMID: 23314838]
[http://dx.doi.org/10.1007/164_2016_6] [PMID: 27316914]
[http://dx.doi.org/10.1093/toxsci/kfs298] [PMID: 23135547]