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Effects of Aqueous Azadirachta indica Extract on Hepatotoxicity in Rats

수용성 님추출물이 랫드의 간 독성에 미치는 영향

  • Park, Kyung-Hun (Chemical Safety Division, National Academy of Agricultural Science) ;
  • Yoon, Hyunjoo (Chemical Safety Division, National Academy of Agricultural Science) ;
  • Han, Beom Seok (Hoseo Toxicological Research Center, Hoseo University) ;
  • Lee, Je-Bong (Agro-material Safety Evaluation Division, National Academy of Agricultural Science) ;
  • Jeong, Mi Hye (Agro-material Safety Evaluation Division, National Academy of Agricultural Science) ;
  • Cho, Namjun (Chemical Safety Division, National Academy of Agricultural Science) ;
  • Om, Ae Son (Dept. of Food Science and Nutrition, Hanyang University) ;
  • Paik, Min-Kyoung (Chemical Safety Division, National Academy of Agricultural Science)
  • 박경훈 (농촌진흥청 국립농업과학원 화학물질안전과) ;
  • 윤현주 (농촌진흥청 국립농업과학원 화학물질안전과) ;
  • 한범석 (호서대 안전성평가센터) ;
  • 이제봉 (농촌진흥청 국립농업과학원 농자재평가과) ;
  • 정미혜 (농촌진흥청 국립농업과학원 농자재평가과) ;
  • 조남준 (농촌진흥청 국립농업과학원 화학물질안전과) ;
  • 엄애선 (한양대학교 식품영양학과) ;
  • 백민경 (농촌진흥청 국립농업과학원 화학물질안전과)
  • Received : 2014.05.14
  • Accepted : 2014.10.20
  • Published : 2014.12.31

Abstract

BACKGROUND: Azadirachta indica Extract(AIE) containing azadirachtin as active ingredient have been used worldwide as environment-friendly organic material having pest control properties. However, the extracts prepared with different solvent and from different plant site is very diverse and have different toxicity. METHODS AND RESULTS: In this study, the four week repeated oral dose toxicity test of aqueous AIE in Sprague-Dawley rats was carried out to investigate the toxic effect of liver, main toxicity target organ of AIE. The male and female rats were divided into 4 groups, respectively; control(0 g/Kg bw), low-dose group(0.5 g/Kg bw), middle-dose(1.0 g/Kg bw) and high-dose group(2.0 g/Kg bw). As a results, relative liver weight increased with dose-dependent of AIE(p<0.05). Serum LDH in all AIE-treated groups were significantly lower than the control in male rats(p<0.05). However, serum GOT and GPT were significantly increased in all male AIE-treated groups in male rats(p<0.05) and, in particular, increase of serum GPT in dose-dependent manner raise the possibility of liver damage. Even through serum GLU was increased significantly in high-dose group in male rats compared to control, there were no significant differences of urinary GLU among all groups(p<0.05). In addition, histopathological examination of the liver did not reveal any lesions in all AIE-treated groups. CONCLUSION: In conclusion, 4 weeks of the repeated oral administration of AIE 2.0 g/Kg to rats has resulted no toxic response in liver. Therefore, AIE was no indicated to have any toxic effect in the SD rats, when it was orally administrated below the dosage 2.0 g/Kg/day for 4weeks.

님추출물은 유효성분(active ingredient)으로 azadirachtin을 함유하여 전세계적으로 충해방제용 유기농업자재로 널리 사용되고 있다. 그러나, 님추출물은 님 원료부위 및 추출용매에 따라 종류가 매우 다양하고 안전성에 크게 차이가 난다고 보고되고 있다. 본 연구에서는 우리나라에서 유기농업자재 제품의 원제로 사용되는 수용성 님추출물이 주요 독성기관인간에 미치는 영향에 대해서 살펴보고자 SD 랫드를 이용하여 4주 반복경구독성시험을 수행하였다. 시험결과, 님추출물 시험물질의 투여 농도가 증가함에 따라 간의 상대중량이 증가하였다(p <0.05). 혈액 생화학분석 결과, 수컷에서 대조군에 비해 시험물질 처리시 혈중 LDH는 감소하였으나 GOT와 GPT가 증가하였으며(p <0.05), 특히 GPT가 시험물질에 농도 의존적으로 증가함에 따라 수컷에서 간 손상의 가능성을 나타내었다. 또한, 고농도로 님추출물 시료를 처리한 경우 수컷의 혈중 GGT가 급격히 증가하였으며 혈중 GLU도 유의적으로 증가하였으나(p <0.05), 뇨 중 GLU는 님추출물의 처리농도증가에 따른 변화가 나타나지 않았다. 간의 조직병리학적 변화를 살펴본 결과 님추출물 시료 처리에 따른 간의 병변도 확인되지 않았다. 따라서 본 시험에 사용된 수용성 님추출물 시료는 혈액 생화학적 분석 결과 수컷에서 간손상의 가능성은 있었으나 조직병리학적 변화는 관찰되지 않았다. 따라서, 수용성 님추출물 2.0 g/Kg 을 4주간 랫드에 경구투여한 결과 간에 독성을 미치지 않고 안전한 것으로 판단된다.

Keywords

References

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