Evaluation of the effect of a bioactive natural product in a mouse model of acute renal failure

[Speaker] Keita Shibata:1
[Co-author] Shohei Kinoshita:1, Terumasa Hashimoto:1, Keiji Hasumi:2, Kazuo Honda:1, Koji Nobe:1
1:Division of Pharmacology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy, Japan, 2:Department of Applied Biological Science, Tokyo University of Agriculture and Technology, Japan

 Acute renal failure is a pathological condition in which renal function rapidly decreases due to ischemia/reperfusion or drugs. The mortality rate associated with acute renal failure in hospitalized critically ill patients exceeds 50%. Long-term hemodialysis is often required even in surviving patients, and a poor prognosis is regarded as a serious problem. However, no effective therapeutic agents have been established. Therefore, the aim of the present study was to evaluate the effect of a bioactive natural product in a mouse model of acute renal failure.
 The right kidney of male ddY mice (30 g) was removed through a small flank incision under isoflurane anesthesia. After a 2-week recovery period, the left renal artery and vein were occluded with an atraumatic clamp for 45 min. Mice with acute renal failure were randomly assigned to the vehicle-treated group, bioactive natural product-treated group (10, 1.0, 0.1, or 0.01 mg/kg), or edaravone-treated group (3 mg/kg). Vehicle, bioactive natural product, or edaravone was intravenously infused at 30-min intervals using a syringe pump 15 min after starting ischemia. Urine flow, urinary albumin, kidney weight, blood urea nitrogen, serum creatinine, creatinine clearance, and urinary excretion of sodium were measured to evaluate renal function. In addition, histological examination of the excised kidney was performed by hematoxylin-eosin staining to evaluate tubule dilation, tubular necrosis, and proteinaceous casts.
 In the acute renal failure model, edaravone improved only urine flow, blood urea nitrogen, serum creatinine, and urinary excretion of sodium; however, the bioactive natural product significantly improved all parameters in a dose-dependent manner. Moreover, edaravone improved acute tubular necrosis of the outer stripe of the medulla and tubular casts in the inner stripe of the medulla, while the bioactive natural product improved the renal tubules of the entire cortex and medulla.
 These results indicate that the bioactive natural product used in the present study shows potential as a new therapeutic agent for acute renal failure. We plan to investigate the mechanism of the effect of this bioactive natural product in acute renal failure.
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