Journal of fish pathology (한국어병학회지)

The Korean Society of Fish Pathology (한국어병학회)
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Effects of amprolium hydrochloride on expression of drug metabolizing enzyme genes in olive flounder Paralichthys olivaceus

Amprolium hydrochloride가 넙치 Paralichthys olivaceus의 약물대사 유전자 발현에 미치는 영향

  • Sang Hyup Park (Department of Aquatic Life Medicine, Gangneung-Wonju National University) ;
  • Chang Han Kim (Department of Aquatic Life Medicine, Gangneung-Wonju National University) ;
  • Jeong-wan Do (Pathology Division, National Institute of Fisheries Science) ;
  • Hye-Sung Choi (Pathology Division, National Institute of Fisheries Science) ;
  • Yi Kyung Kim (Department of Aquatic Life Medicine, Gangneung-Wonju National University)
  • 박상협 (강릉원주대학교 수산생명의학과) ;
  • 김창환 (강릉원주대학교 수산생명의학과) ;
  • 도정완 (국립수산과학원 병리연구과) ;
  • 최혜승 (국립수산과학원 병리연구과) ;
  • 김이경 (강릉원주대학교 수산생명의학과)
  • Received : 2023.08.30
  • Accepted : 2023.11.13
  • Published : 2023.12.31
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Abstract

This study was undertaken to evaluate the effect of amprolium hydrochloride on detoxification process of olive flounder Paralichthys olivaceus. A series of two experiment was performed based on the LD50 value obtained for amprolium. First, thirty flounder (average weight 230.27 g; average length 27.99 cm) was randomly allocated into five groups. Treatment was carried out using intra-muscular injection of amprolium at the dose levels of 4, 8, 16, and 32 mg/kg body weight. At 8, 24 and 48 h post injection, liver and kidney were collected for expression assay of drug metabolizing enzymes and pro-inflammatory cytokine genes. We found that the interleukin-1β (IL-1β) mRNA level were induced at 32 mg/kg and CYP1A genes showed the opposite pattern, while UDP-glucuronosyl-transferase (UGT1A7) and GST were significantly reduced in the liver. Moreover, the suppression of drug metabolizing enzymes and cytokine gene in the kidney was observed after treatment. Another treatment was carried out using intramuscular injection with 4, 8, 16, and 32 mg/kg and 60, 80, 100, 120 mg/kg body weight. At 6 days post injection, liver was collected. The IL-1β expression was markedly induced in the experimental group treated with 4 mg/kg. In addition, glutathione S-transferase (GST) mRNA level was higher in the group with 4 mg/kg. In conclusion, our data suggests that amprolium seem to cause direct or indirect physical, or biological toxicity of flounders, although this drug is considered one of the safest synthetic anticoccidial drugs of the livestock industry.

본 연구에서는 넙치의 해독 과정에서 amprolium hydrochloride의 영향을 평가하기 위해 수행되었다. 이전 연구에서 보고된 amprolium의 LD50 값을 이용하여 두 가지 실험을 진행하였다. 첫 번째는 30마리의 넙치를 5개의 대조군 및 실험군으로 나누었고 4, 8, 16, 32 mg/kg 용량의 amprolium을 근육 내 주사 투여하였다. 주사 후 8, 24, 48 시간에 간과 신장을 적출하여 약물 대사 효소와 전염증성 사이토카인 유전자의 발현을 분석하였다. 32 mg/kg 용량의 실험군에서 IL-1β mRNA의 높은 발현을 확인하였고, CYP1A는 이와 반대의 결과를 보였으며, 간에서 UGT와 GST mRNA의 발현은 유의하게 감소하는 것을 확인하였다. 또한 신장에서 amprolium 주사 투여 후 약물 대사 효소와 사이토카인 유전자의 억제가 관찰되었다. 또 다른 실험에서는 4, 8, 16, 32 mg/kg과 60, 80, 100, 120 mg/kg의 용량을 설정하여 근육 내 주사 투여하였다. 주사를 완료하고 6일 후 간을 적출하여 유전자의 발현을 확인하였다. IL-1β의 발현은 4 mg/kg 용량 실험군에서 유의적으로 매우 높은 발현을 보였다. GST의 mRNA 발현 또한 4 mg/kg 용량 실험군에서 높은 발현을 보였다. 결론적으로 우리의 결과는 amprolium이 가축 산업의 가장 안전한 합성 항콕시듐 약물 중 하나로 간주되지만 넙치의 간접 또는 직접적인 물리적 또는 생물학적 독성을 유발하는 것으로 판단된다.

Keywords

Acknowledgement

이 논문은 국립수산과학원(P2023202, 넙치쿠도아충 저감화 연구)의 지원에 의해 진행되었음.

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