title: Anti-nephrolithic potential of catechin in melamine-related urolithiasis via the inhibition of ROS, apoptosis, phospho-p38, and osteopontin in male Sprague-Dawley rats.
abstract: The addition of melamine to infant formula may cause urolithiasis in humans and animals. This study examined the effects of catechin, an antioxidant, on melamine-cyanuric acid mixture (MCM)-induced crystallization in vitro and in vivo. In an in vitro study, crystal formation induced by an MCM was evaluated in media under various pH conditions and with catechin co-treatment. In an in vivo study, rats were administered an MCM (400 mg/kg, 1:1, via oral feeding tube) for four weeks and co-treated with catechin, after which crystal formation was observed. Oxidative stress biomarkers and nephrotoxicity were measured. Apoptotic cells were examined using the TUNEL assay. Phospho-p38 and osteopontin were evaluated via immunohistochemistry and Western blotting. MCM-induced crystal formation was pH-dependent in conditioned media, and catechin reduced the overall number of crystals. In the in vivo study, catechin suppressed MCM-induced protein expression and apoptosis in rats. Catechin consistently reduced the MCM-mediated production of renal malondialdehyde (MDA) and urinary 8-isoprostane (8-IP) in MCM-treated rats. The activities of antioxidant enzymes such as superoxide dismutase (SOD) were enhanced by catechin. Catechin consistently and significantly reduced levels of renal crystals and nephrotoxicity. Our findings suggest that catechin exhibits anti-nephrolithic potential by chemically inhibiting the formation of crystals and by inhibiting reactive oxygen species, apoptosis, phospho-P38, and osteopontin signaling in rats.
authors.affiliation: a Department of Urology , Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, The Second Hospital of Lanzhou University , Lanzhou, Gansu Province, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Wu
authors.forename: P
authors.initials: P
authors.lastname: Shang
authors.forename: J
authors.initials: J
authors.lastname: Bao
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: Z
authors.initials: Z
authors.lastname: Yue
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000494:pharmacology / Q000627:therapeutic use*; D003460:Crystallization; D004353:Drug Evaluation, Preclinical; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D053495:Osteopontin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013662:Tea; D014227:Triazines / Q000737:chemistry / Q000633:toxicity*; D052878:Urolithiasis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; C506897:Spp1 protein, rat; D013662:Tea; D014227:Triazines; D053495:Osteopontin; D002392:Catechin; D048051:p38 Mitogen-Activated Protein Kinases; C004632:cyanuric acid; C011907:melamine
keywords: apoptosis; catechin; melamine; osteopontin; urolithiasis