caa a22 4500 606234098 CHVBK 20210128101235.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s11010-014-2243-8 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2243-8 The selective NADPH oxidase inhibitor apocynin has potential prophylactic effects on melamine-related nephrolithiasis in vitro and in vivo [Elektronische Daten] [Xiaoran Li, Jianzhong Lu, Panfeng Shang, Junsheng Bao, Zhongjin Yue] The objective of this study is to examine the effects of apocynin on melamine-cyanuric acid mixture (MCM)-induced nephrolithiasis in vitro and in vivo. For the in vitro experiments, changes in oxidative stress (OS) markers and the expression of osteopontin (OPN) and phospho-p38 (p-p38) were measured to assess the effects of apocynin treatment after MCM-induced crystallization in HK-2 cells, a human renal epithelial-derived cell line. For in vivo studies, the potential effects of apocynin in preventing and treating nephrolithiasis were analyzed with a MCM-induced nephrolithiasis rat model, and urea and creatinine levels were measured. Urinary 8-IP (a product of lipid peroxidation) and malondialdehyde levels and superoxide dismutase activity were assessed in the kidneys as markers of renal OS. The kidneys were removed, weighed, and subjected to histopathological examination. The urolithiasis-associated proteins p-p38 and OPN were evaluated by immunohistochemistry and Western blotting. Apocynin treatment prevented the MCM-induced changes in OS and in OPN and p-p38 expression in HK-2 cells. For in vivo experiments, the expression of OS markers, renal OPN, and p-p38 increased after MCM administration, and these increases were diminished by apocynin. In addition, apocynin prevented MCM-induced renal crystallization. Moreover, prophylactic apocynin treatment reduced MCM-induced nephrotoxicity. After therapeutic apocynin treatment in nephrolithic rats, OS decreased, but the other indicators did not improve significantly. Prophylactic apocynin administration reduced renal melamine-related-crystal deposition, potentially by modulating OS and thereby decreasing p-p38 and OPN expression. Springer Science+Business Media New York, 2014 Nephrolithiasis nationallicence Melamine nationallicence Oxidative stress nationallicence Apocynin nationallicence Rats nationallicence MCM : Melamine-cyanuric acid mixture nationallicence OS : Oxidative stress nationallicence SD : Sprague-Dawley nationallicence SOD : Superoxide dismutase nationallicence ROS : Reactive oxygen species nationallicence MDA : Malondialdehyde nationallicence MAPK : Mitogen-activated protein kinase nationallicence ERK : Extracellular signal-regulated kinase nationallicence OPN : Osteopontin nationallicence BUN : Blood urea nitrogen nationallicence Cr : Serum creatinine nationallicence JNK : c-Jun NH2-terminal protein kinase nationallicence Li Xiaoran Department of Urology, Gansu Nephro-Urological Clinical Center, Institute of Urology, The Second Hospital of Lanzhou University, 82 Cui Ying Men, 730030, Lanzhou, Gansu, People's Republic of China aut Lu Jianzhong Department of Urology, Gansu Nephro-Urological Clinical Center, Institute of Urology, The Second Hospital of Lanzhou University, 82 Cui Ying Men, 730030, Lanzhou, Gansu, People's Republic of China aut Shang Panfeng Department of Urology, Gansu Nephro-Urological Clinical Center, Institute of Urology, The Second Hospital of Lanzhou University, 82 Cui Ying Men, 730030, Lanzhou, Gansu, People's Republic of China aut Bao Junsheng Department of Urology, Gansu Nephro-Urological Clinical Center, Institute of Urology, The Second Hospital of Lanzhou University, 82 Cui Ying Men, 730030, Lanzhou, Gansu, People's Republic of China aut Yue Zhongjin Department of Urology, Gansu Nephro-Urological Clinical Center, Institute of Urology, The Second Hospital of Lanzhou University, 82 Cui Ying Men, 730030, Lanzhou, Gansu, People's Republic of China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 399/1-2(2015-01-01), 167-178 0300-8177 399:1-2<167 2015 399 11010 https://doi.org/10.1007/s11010-014-2243-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2243-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Xiaoran Department of Urology, Gansu Nephro-Urological Clinical Center, Institute of Urology, The Second Hospital of Lanzhou University, 82 Cui Ying Men, 730030, Lanzhou, Gansu, People's Republic of China aut NATIONALLICENCE 700 1- Lu Jianzhong Department of Urology, Gansu Nephro-Urological Clinical Center, Institute of Urology, The Second Hospital of Lanzhou University, 82 Cui Ying Men, 730030, Lanzhou, Gansu, People's Republic of China aut NATIONALLICENCE 700 1- Shang Panfeng Department of Urology, Gansu Nephro-Urological Clinical Center, Institute of Urology, The Second Hospital of Lanzhou University, 82 Cui Ying Men, 730030, Lanzhou, Gansu, People's Republic of China aut NATIONALLICENCE 700 1- Bao Junsheng Department of Urology, Gansu Nephro-Urological Clinical Center, Institute of Urology, The Second Hospital of Lanzhou University, 82 Cui Ying Men, 730030, Lanzhou, Gansu, People's Republic of China aut NATIONALLICENCE 700 1- Yue Zhongjin Department of Urology, Gansu Nephro-Urological Clinical Center, Institute of Urology, The Second Hospital of Lanzhou University, 82 Cui Ying Men, 730030, Lanzhou, Gansu, People's Republic of China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 399/1-2(2015-01-01), 167-178 0300-8177 399:1-2<167 2015 399 11010