Protective effects of antithrombin on puromycin aminonucleoside nephrosis in rats.
We investigated the effects of antithrombin, a plasma inhibitor of coagulation factors, in rats with puromycin aminonucleoside-induced nephrosis, which is an experimental model of human nephrotic syndrome. Antithrombin (50 or 500 IU/kg/i.v.) was administered to rats once a day for 10 days immediately after the injection of puromycin aminonucleoside (50 mg/kg/i.v.). Treatment with antithrombin attenuated the puromycin aminonucleoside-induced hematological abnormalities. Puromycin aminonucleoside-induced renal dysfunction and hyperlipidemia were also suppressed. Histopathological examination revealed severe renal damage such as proteinaceous casts in tubuli and tubular expansion in the kidney of control rats, while an improvement of the damage was seen in antithrombin-treated rats. In addition, antithrombin treatment markedly suppressed puromycin aminonucleoside-induced apoptosis of renal tubular epithelial cells. Furthermore, puromycin aminonucleoside-induced increases in renal cytokine content were also decreased. These findings suggest that thrombin plays an important role in the pathogenesis of puromycin aminonucleoside-induced nephrotic syndrome. Treatment with antithrombin may be clinically effective in patients with nephrotic syndrome.
Pharmaceutical Research Laboratory, Research Division, Nihon Pharmaceutical Co Ltd, Narita-City, Chiba, Japan. j.yamashita@nihon-pharm.co.jp <j.yamashita@nihon-pharm.co.jp>
Junji
J
Yamashita
Kenji
K
Nakajima
Yoichi
Y
Ohno
Yoshiaki
Y
Kaneshiro
Takato
T
Matsuo
Hitoshi
H
Tanaka
Kenji
K
Kaneko
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D000991:Antithrombins / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006949:Hyperlipidemias / Q000378:metabolism / Q000517:prevention & control; D020287:In Situ Nick-End Labeling; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009404:Nephrotic Syndrome / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011507:Proteinuria / Q000378:metabolism / Q000517:prevention & control; D011692:Puromycin Aminonucleoside; D051381:Rats; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
D000925:Anticoagulants; D000991:Antithrombins; D016207:Cytokines; D011692:Puromycin Aminonucleoside; D013917:Thrombin