European Journal of Anatomy

Official Journal of The Spanish Society of Anatomy
Cover Volume 21 - Number 4
Eur J Anat, 21 (4): 279-286 (2017)

Effects of nafamostat mesilate, a protease Inhibitor, on ischemia/reperfusion-induced kidney injury in mice

Jae Chul Lee 1,2

1Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-Gil, Bundang-Gu, Seongnam-si, Gyeonggi-do 463707, Republic of Korea, 2Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea

ABSTRACT Ischemia is induced when blood flow to an organ is interrupted, and re-establishing blood flow is essential to prevent ongoing hypoxic injury, although it paradoxically imparts further injury. Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has been used in patients undergoing hemodialysis who are at a high risk of bleeding. To determine the protective effect of NM on ischemia-reperfusion injury (IRI) in a mouse renal IRI model, NM was administered as a pre- and post-treatment or during ischemia reperfusion and compared to a control group. Mice were bilaterally nephrectomized and subjected to 40 min of renal pedicle occlusion followed by 24 h reperfusion. NM (240 μg/kg) significantly improved kidney function and lowered serum creatinine and blood urea nitrogen levels. Consistently, NM inhibited collagen formation in kidney tissues. NM treatment attenuated the effects of ischemia/reperfusion on kidney tissues and significantly inhibited activation of Toll-like receptor 4, nuclear factor kappa-light-chain-enhancer of activated B cells-phospho-65 (NF- kB-p65), phospho-inhibitor of NF-κβa, and inducible nitric oxide synthase (iNOS). NM treatment also decreased expression of Bcl-2, Caspase-3 and Bax in kidney tissues, which has been linked with induction of apoptosis in kidney tissues. Our studies suggest that NM may be a novel therapeutic agent to prevent and treat kidney IRI, in which iNOS and/or NF-κβ are upregulated. The exact regulatory mechanism and its functional significance require further elucidation.

Keywords: Apoptosis Gene expression Ischemia-reperfusion injury Nafamostat mesilate

European Journal of anatomy
ISSN 2340-311X (Online)