Melamine Impairs Renal and Vascular Function in Rats.
Melamine incident, linked to nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products, was unprecedentedly grave in China in 2008 as little was known about the mechanistic process leading to renal dysfunction in affected children. This study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring. A combination of approaches employed includes functional studies in rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry, and detection of plasma and renal melamine. We provide mechanistic evidence showing for the first time that melamine reduces renal blood flow and impairs renal and vascular function associated with overexpression of inflammatory markers, transforming growth factor-β1, bone morphogenic protein 4 and cyclooxygenase-2 in kidney and renal vasculature. Melamine also induces renal inflammation and fibrosis. More importantly, melamine causes nephropathies in offsprings from pregnant rat exposed to melamine during pregnancy, as well as in neonatal rat exposed to melamine afterbirth, thus supporting the clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products.
School of Biomedical Sciences, Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.
Xiao Yu
XY
Tian
School of Biomedical Sciences, Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.
Wing Tak
WT
Wong
School of Biomedical Sciences, Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.
Chi Wai
CW
Lau
Department of Diagnostic Radiology and Organ Imaging, Chinese University of Hong Kong, Hong Kong.
Yi-Xiang
YX
Wang
School of Biomedical Sciences, Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.
Wai San
WS
Cheang
School of Biomedical Sciences, Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.
Jian
J
Liu
School of Biomedical Sciences, Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.
Ye
Y
Lu
School of Biomedical Sciences, Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.
Huihui
H
Huang
School of Biomedical Sciences, Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.
Yin
Y
Xia
School of Life Sciences, Chinese University of Hong Kong, Hong Kong.
Zhen Yu
ZY
Chen
Hong Kong Government Laboratory, Hong Kong.
Chuen-Shing
CS
Mok
Hong Kong Government Laboratory, Hong Kong.
Chau-Ming
CM
Lau
School of Biomedical Sciences, Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong.
Yu
Y
Huang
D000109:Acetylcholine / Q000494:pharmacology; D058186:Acute Kidney Injury / Q000209:etiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001783:Blood Flow Velocity / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D005260:Female; D005506:Food Contamination / Q000032:analysis; D007668:Kidney / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D007669:Kidney Calculi / Q000209:etiology; D018811:Maternal Exposure; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000187:drug effects* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014227:Triazines / Q000097:blood / Q000633:toxicity*
D015415:Biomarkers; C525811:Bmp4 protein, rat; D055415:Bone Morphogenetic Protein 4; D053773:Transforming Growth Factor beta1; D014227:Triazines; D051546:Cyclooxygenase 2; C011907:melamine; D000109:Acetylcholine