Oral hydrogen water prevents chronic allograft nephropathy in rats.
Reactive oxygen species (ROS) contribute to the development of interstitial fibrosis and tubular atrophy seen in chronic allograft nephropathy (CAN). As molecular hydrogen gas can act as a scavenger of ROS, we tested the effect of treatment with hydrogen water (HW) in a model of kidney transplantation, in which allografts from Lewis rats were orthotopically transplanted into Brown Norway recipients that had undergone bilateral nephrectomy. Molecular hydrogen was dissolved in water and recipients were given HW from day 0 until day 150. Rats that were treated with regular water (RW) gradually developed proteinuria and their creatinine clearance declined, ultimately leading to graft failure secondary to CAN. In contrast, treatment with HW improved allograft function, slowed the progression of CAN, reduced oxidant injury and inflammatory mediator production, and improved overall survival. Inflammatory signaling pathways, such as mitogen-activated protein kinases, were less activated in renal allografts from HW-treated rats as compared with RW-treated rats. Hence, oral HW is an effective antioxidant and antiinflammatory agent that prevented CAN, improved survival of rat renal allografts, and may be of therapeutic value in the setting of transplantation.
Cardinal
Jon S
JS
Department of Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA.
Zhan
Jianghua
J
Wang
Yinna
Y
Sugimoto
Ryujiro
R
Tsung
Allan
A
McCurry
Kenneth R
KR
Billiar
Timothy R
TR
Nakao
Atsunori
A
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects; D006859:Hydrogen / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D014184:Transplantation, Homologous; D015430:Weight Gain / Q000187:drug effects
D000975:Antioxidants; D015415:Biomarkers; D006859:Hydrogen