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Kidney Week

Abstract: FR-PO369

The Antioxidant Activity of Neurotropin Contributes to the Kidney Protective Effect

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Fukunaga, Masaki, Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
  • Uchida, Akemi, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
  • Sueyoshi, Miyu, Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
  • Maeda, Hitoshi, Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
  • Narita, Yuki, Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
  • Watanabe, Hiroshi, Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
  • Maruyama, Toru, Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
  • Seo, Hakaru, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
  • Hirata, Sumio, Faculty of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan
  • Kadowaki, Daisuke, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
Background

Neurotropin (NTP) is an extract from inflamed cutaneous tissue of rabbits inoculated with vaccinia virus and contains various non-protein components. NTP has long been used for the treatment of neuropathic pain such as postherpetic neuralgia. Recently, NTP have been reported that various organ protective effects by its antioxidant action. Furthermore, it is also suggested that NZ-419, which is one of the components of NTP, has the antioxidant activity and contributes to the renoprotective effect. Therefore, the aim of this study is to evaluate the antioxidant activity and renoprotective effect of NTP by in vitro and in vivo.

Methods

The radical scavenging ability for reactive oxygen species (ROS) was examined by electron spin resonance (ESR) method, chemiluminescence method or fluorescence analysis. The effect of NTP on oxidative stress induced by uremic toxins was evaluated using human renal proximal tubule epithelial cells (HK-2). Furthermore, 5/6 nephrectomized rats (CKD) were divided into 3 groups (CKD, CKD + NTP, and CKD + aspirin) and were orally administered each drug once daily for 4 weeks. Survival rate, kidney function parameters, oxidative stress marker, and kidney fibrosis were measured.

Results

NTP had concentration-dependent O2・- and ONOO- scavenging ability and scavenged OH at high concentrations. The inhibitory effect on intracellular ROS production was observed in only H2O2 under the simultaneous addition of NTP and irritant. On the other hand, the irritant-induced ROS production was inhibited under the preincubation of NTP for 9 hour. Survival rate of CKD rats was shown a trend of decreased in the aspirin group. NTP didn’t affect survival rate and had a tendency to suppress kidney damage. Also, compared to the CKD group, the NTP group was observed that thiol concentration, antioxidant marker, increased in blood and decreased in fibrotic area in kidney.

Conclusion

In this study, it is considered that NTP has the direct radical scavenging ability and alters intracellular signal transduction to suppress oxidative stress. In conclusion, NTP may contribute to the renoprotective effect by not only the antioxidant effect but also the antifibrosis.