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The protective effect of hypoxic therapy on paraquat-induced toxicity rat model

백서를 이용한 고독성 제초제 파라쿼트 중독 치료를 위한 저농도산소요법의 효과 연구

  • Kim, Hoon (Department of Emergency Medicine, College of Medicine, Chungbuk National University) ;
  • Min, Jin-Hong (Department of Emergency Medicine, College of Medicine, Chungbuk National University) ;
  • Han, Kyu-Hong (Department of Emergency Medicine, College of Medicine, Chungbuk National University) ;
  • Kang, Joon-Ho (Department of Emergency Medicine, College of Medicine, Chungbuk National University)
  • 김훈 (충북대학교 의과대학 응급의학교실) ;
  • 민진홍 (충북대학교 의과대학 응급의학교실) ;
  • 한규홍 (충북대학교 의과대학 응급의학교실) ;
  • 강준호 (충북대학교 의과대학 응급의학교실)
  • Received : 2013.11.20
  • Accepted : 2013.04.10
  • Published : 2014.04.30

Abstract

Paraquat (PQ) is a very effective and widely used herbicide that was commercially introduced in 1962. In this study, instead of using antioxidants like in the past, to inhibit the formation of PQ-induced ROS, we attempted to reduce the oxygen concentration by using non-lethal hypoxia therapy. Therefore, we studied the toxicity of PQ in vivo, analyzed the major effects of ROS on the targeted lung tissue and compared the results with the gross histological changes after the cell protective effect of non-lethal hypoxia therapy. In vivo studies demonstrated that low-concentration oxygen therapy (i.e., 10-12% oxygen) in rats administered with PQ was associated with a higher survival rate than in rats that received only PQ. In vivo non-lethal hypoxia treatment showed better survival and less lung tissue damage. Using a hypoxic/anaerobic incubator with integrated multifaceted molecular analysis, including MDA assay, glutathione assay, and SOD assay, we established an optimal, significantly reduced in vivo non-lethal hypoxia treatment by exploiting the PQ-induced cytotoxicity responses.

본 연구는 제초제 음독 중에서 가장 치명률이 높은 파라쿼트 중독의 독성 감소를 위하여 파라쿼트 독성 기전으로 알려진 파라쿼트 유도성 활성산소종을 감소시키기 위해 기존의 항산화제들 치료제와는 달리, 사전에 산소 농도를 줄여서 파라쿼트에 의한 활성 산소종 발생 자체를 줄이는 저농도 산소요법의 유용성을 연구하였다. 이를 위해 백서를 활용하여 생존률 및 파라쿼트에 의한 활성 산소종의 영향을 가장 빠르고 많이 받는 폐조직의 육안적 조직학적 변화를 비교 분석함으로써 세포 독성 상황에서 저농도 산소요법의 효과를 분석하였다. 그 결과 저농도 산소요법을 처리한 군에서 유의한 생존률 증가와 함께 H&E Stain결과에서는 염증세포 증가 및 Aveolar space에 부종 소견이 저농도 산소요법을 함께 시행한 군에서 완화된 소견을 확인할 수 있었다. 또한 파라쿼트의 독성기전의 핵심인 산화스트레스발생 분석을 시행한 결과, MDA assay, Glutathione assay 및 SOD Assay모두에서 파라쿼트는 산화스트레스를 증가하지만 파라쿼트와 함께 저농도 산소요법을 처리한 경우 산화 스트레스가 감소함을 증명하였다. 이를 통해 본 연구는 임상에서 파라쿼트 중독에 대한 새로운 치료 대안으로서의 기초 연구로서 활용이 기대된다.

Keywords

References

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