Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
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Anti-oxidative and Anti-inflammatory Effects of Genistein in BALB/c Mice Injected with LPS

LPS 주사한 BALB/c 마우스에서 Genistein의 산화적 스트레스 억제효과 및 항염증 효과

  • Cho, Hye-Yeon (Paik Inje Memorial Clinical Research Institute, School of Medicine, Inje University) ;
  • Noh, Kyung-Hee (BK21 Center of Smart Foods and Drugs, Food Science Institute, and Biohealth Product Research Center, Inje University) ;
  • Cho, Mi-Kyung (BK21 Center of Smart Foods and Drugs, Food Science Institute, and Biohealth Product Research Center, Inje University) ;
  • Jang, Ji-Hyun (BK21 Center of Smart Foods and Drugs, Food Science Institute, and Biohealth Product Research Center, Inje University) ;
  • Lee, Mi-Ok (Korean Food & Culinary Arts Department, Youngsan University) ;
  • Kim, So-Hee (School of Culinary Art & Baking Technology, Dong-Ju College) ;
  • Song, Young-Sun (BK21 Center of Smart Foods and Drugs, Food Science Institute, and Biohealth Product Research Center, Inje University)
  • 조혜연 (인제대학교 의과대학 백인제기념 임상의학연구소) ;
  • 노경희 (인제대학교 BK21 식의약생명공학과, 식품과학연구소 및 바이오헬스 소재연구센터) ;
  • 조미경 (인제대학교 BK21 식의약생명공학과, 식품과학연구소 및 바이오헬스 소재연구센터) ;
  • 장지현 (인제대학교 BK21 식의약생명공학과, 식품과학연구소 및 바이오헬스 소재연구센터) ;
  • 이미옥 (영산대학교 한국식품조리학과) ;
  • 김소희 (동주대학 외식조리제과계열) ;
  • 송영선 (인제대학교 BK21 식의약생명공학과, 식품과학연구소 및 바이오헬스 소재연구센터)
  • Published : 2008.09.30
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Abstract

This study was carried out to investigate the anti-oxidative and anti-inflammatory actions of genistein in BALB/c mice injected with lopopolysaccharide (LPS), called endotoxin. Mice (10 weeks of age) weighing approximately 20 g were divided into 4 groups. Endotoxin shock was induced by intraperitoneal injection of LPS (100 mg/kg BW). LPS and genistein+LPS groups were injected with LPS 30 min after phosphate buffered saline (PBS) solution and genistein (200 mg/kg BW) injections, respectively. Genistein group was injected with genistein, followed by PBS, while PBS group received two injections of PBS. Superoxide anion generation of peritoneal macrophage cells was significantly (p<0.05) lower in the genistein+LPS group than in the LPS injection group at 8 h after intraperitoneal injection, while SOD activity was significantly higher in genistien+LPS group than LPS group. Tumor necrosis factor-$\alpha$ levels of plasma were significant lower (p<0.05) in the genistein+LPS injection group than LPS group at 8 h after intraperitoneal injection. Plasma TBARS was lower in genistein+LPS group than LPS group, while hepatic TBARS were not different among groups. Hepatic glutathione concentrations and antioxidant enzyme activities were ignificantly higher in the genistein+LPS group than in the LPS group at 1 h and 8 h after intraperitoneal injection. Nuclear factor-kappa B (NF-${\kappa}B$) transactivation was significantly (p<0.05) inhibited in LPS group. These results demonstrate genistein may ameliorate inflammatory diseases through inhibition of NF-${\kappa}B$ transactivation and oxidative stress, which may be mediated partially by anti-oxidative effect of genistein.

본 연구에서는 내독소인 LPS로 산화적 스트레스를 유발시킨 BALB/c mice에 genistein을 투여하였을 때 TNF-$\alpha$, TBARS, superoxide anion 농도와 GSH, 항산화 효소계 활성, 그리고 NF-${\kappa}B$ transactivation에 미치는 영향을 조사하여 genistein이 내독소에 의한 산화적 스트레스와 염증반응을 억제하는 효과가 있는지 알아보고자 하였다. 평균체중 20 g인 BALB/c mice 암컷 120수를 30수씩 완전임의배치로 4군으로 분류하여 PBS군(대조군)은 PBS를 복강 속으로 투여 후 30분경과 후에 다시 PBS를 투여하였으며, genistein군은 genistein을 체중 kg당 200 mg으로 투여한 30분 후 PBS를 투여하였다. LPS군은 LPS를 처리한 군으로 PBS 투여 30분 후 LPS를 체중 kg당 100 mg 농도로 복강 투여하였고, genistein+LPS군은 체중 kg당 genistein 200 mg을 투여 30분 후 LPS를 체중 kg당 100 mg을 투여하였다. 마지막 투여 1시간, 4시간, 8시간 경과 후 mouse의 안와정맥으로부터 혈액을, 복강으로부터 복강대식세포와 간을 취하였다. LPS 투여 8시간 경과 후 LPS군의 ${O_2}^-$ 생성량은 현저하게 증가하였으며 geinstein+LPS군은 genistein 대조군, PBS군과 비슷한 수준을 유지하였다. 반면 SOD 활성은 geinstein+LPS군이 LPS군에 비해 유의적으로 높은 수준이었다. 혈장에서의 TNF-$\alpha$ 수준은 LPS 투여 8시간 후 genstein+LPS군이 LPS군보다 유의적으로 낮은 수준을 보였다. LPS 투여는 항산화 효소계 활성과 GSH의 수준을 감소하였으나, genistein을 투여한 genistein+LPS군은 LPS군에 비해 GSH 농도와 catalase, GSH-px, GSH-reductase 활성이 모두 유의적으로 증가하는 결과를 보였다. 간에서의 NF-${\kappa}B$ transactivation 정도는 LPS 투여 후 1시간, 4시간 경과 후에 PBS군에 비해 LPS군과 genistein+LPS군에서 유의적으로 높은 수준이었으나 8시간 경과 후 LPS군은 증가하는 반면 genistein+LPS군은 변화하지 않았다. 이상의 결과를 요약해보면 LPS의 투여는 혈장과 간의 산화적 스트레스와 염증반응을 촉진하는 것으로 나타났으며 LPS 투여 전 공급한 genistein은 LPS로 유도된 산화적 스트레스와 염증반응을 항산화 효소계 활성 증가와 NF-${\kappa}B$ transactivation 억제, TNF-$\alpha$ 생성 저하 등의 기작으로 세포내의 과산화수준을 수준을 낮추고 GSH를 증가시켜 산화적 스트레스를 억제하는 것으로 사료된다.

Keywords

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