Re: 치매의 원인들 4. 곰팡이 독소(마이코톡신 - 아플라톡신)

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Ecotoxicol Environ Saf

. 2019 Oct 30;182:109407.

 doi: 10.1016/j.ecoenv.2019.109407. Epub 2019 Jul 4.

Chronic neurodegeneration by aflatoxin B1 depends on alterations of brain enzyme activity and immunoexpression‎ of astrocyte in male rats

Ahmed Alsayyah 1, Reda ElMazoudy 2, Mashael Al-Namshan 3, Meneerah Al-Jafary 3, Nouf Alaqeel 3

Affiliations expand

• PMID: 31279280
• DOI: 10.1016/j.ecoenv.2019.109407

Abstract

Aflatoxin B1 poses the greatest risk among the mycotoxins to target-organisms particularly human, however, no studies addressed the neurotoxicity of chronic exposure of aflatoxin. The oral dose level 1/600th of LD50 for 30, 60, and 90 days was used for three aflatoxin groups, respective to negative and vehicle control groups. Activity levels of brain antioxidants viz: superoxide dismutase, catalase, glutathione, and glutathione peroxidase significantly decreased in the three experimental durations in time-dependent trend, in contrast, lipid peroxidation showed a significant increase compared to controls. Significantly, chronic-dependent increase trend was noticed in the AF60 and AF90 group for acid phosphatase (16.1%, 35.2%), alkaline phosphatase (32.1%, 50.8%), aspartate aminotransferase (38.7%, 120.0%) and lactate dehydrogenase (30.6%, 42.1%) activities, respectively. However, a significant 23.7% decrease in the brain creatine kinase activity following 90 days of AFB1administration. Chronic administration of aflatoxin also causes alterations in activities of protein carbonyl with a maximum increase (twofold) after 90 days. Further, histopathological and immunohistochemical results confirmed time-related vasodilation, necrosis and astrocytes gliosis by high glial fibrillary acidic protein immunostaining in response to AFB1. These findings infer that long-term exposure to AFB1 results in several pathophysiological circumstances in a duration-dependent manner concerning neurodegeneration especially Alzheimer's disease.

환경 오염 물질에 대한 노출은 파킨슨병(PD)과 알츠하이머병(AD)과 같은 신경 퇴행성 질환의 발병에 중요한 역할을 할 수 있습니다. 스페인에서는 처음으로 라 리오하 지역의 신경 퇴행성 질환 환자(44명, 24명)와 건강한 동반자(25명)의 혈장 내 19가지 진균 독소 수치를 분석했습니다. 연구된 곰팡이 독소는 아플라톡신 B1, B2, G1, G2 및 M1, T-2 및 HT-2, 오크라톡신 A(OTA) 및 B(OTB), 제랄레논, 스테리그마토시스틴(STER), 니발레놀, 데옥시니발레놀, 3-아세틸데옥시니발레놀, 15-아세틸데옥시니발레놀, 디아세톡시르페놀, 네오솔라니올, 다이아세톡시르페놀, 푸사레논-X 등 총 9종입니다. 잠재적 대사산물을 검출하기 위해 β-글루쿠로니다제/아릴설파타제로 처리하기 전후에 샘플을 LC-MS/MS로 분석했습니다. 샘플에서는 OTA, OTB 및 STER만 검출되었습니다. OTA는 효소 처리 전(샘플의 77%)과 후(89%)에 모두 존재한 반면, OTB는 처리 전(13%)에만 검출될 수 있었습니다. 건강한 반려동물과 환자 간에 통계적으로 유의미한 OTA 차이가 관찰되었지만, 관찰된 차이는 질병 자체보다는 성별(남성의 OTA 수치가 더 높음, p-값 = 0.0014)과 더 관련이 있는 것으로 보입니다. STER은 효소 치료 후에만 나타났습니다(88%). STER에 대한 통계 분석 결과, 건강한 대조군과 환자군은 항상 다른 분포를 보였습니다(환자군 > 대조군, p-값 <0.0001). 놀랍게도 STER 수치는 여성의 경우 나이와 약한 양의 상관관계가 있는 반면(rho = 0.3384), 남성의 경우 특히 나이가 들면서 수치가 감소하는 것으로 나타났습니다(rho = -0.4643).

Keywords: Aflatoxin; Antioxidants; Brain enzymes; Glial fibrillary acid protein; Neurodegeneration.

Ecotoxicol Environ Saf

•  
•  
•  

. 2019 Oct 30;182:109407.

 doi: 10.1016/j.ecoenv.2019.109407. Epub 2019 Jul 4.

Chronic neurodegeneration by aflatoxin B1 depends on alterations of brain enzyme activity and immunoexpression‎ of astrocyte in male rats

Ahmed Alsayyah 1, Reda ElMazoudy 2, Mashael Al-Namshan 3, Meneerah Al-Jafary 3, Nouf Alaqeel 3

Affiliations expand

• PMID: 31279280
• DOI: 10.1016/j.ecoenv.2019.109407

Abstract

Aflatoxin B1 poses the greatest risk among the mycotoxins to target-organisms particularly human, however, no studies addressed the neurotoxicity of chronic exposure of aflatoxin. The oral dose level 1/600th of LD50 for 30, 60, and 90 days was used for three aflatoxin groups, respective to negative and vehicle control groups. Activity levels of brain antioxidants viz: superoxide dismutase, catalase, glutathione, and glutathione peroxidase significantly decreased in the three experimental durations in time-dependent trend, in contrast, lipid peroxidation showed a significant increase compared to controls. Significantly, chronic-dependent increase trend was noticed in the AF60 and AF90 group for acid phosphatase (16.1%, 35.2%), alkaline phosphatase (32.1%, 50.8%), aspartate aminotransferase (38.7%, 120.0%) and lactate dehydrogenase (30.6%, 42.1%) activities, respectively. However, a significant 23.7% decrease in the brain creatine kinase activity following 90 days of AFB1administration. Chronic administration of aflatoxin also causes alterations in activities of protein carbonyl with a maximum increase (twofold) after 90 days. Further, histopathological and immunohistochemical results confirmed time-related vasodilation, necrosis and astrocytes gliosis by high glial fibrillary acidic protein immunostaining in response to AFB1. These findings infer that long-term exposure to AFB1 results in several pathophysiological circumstances in a duration-dependent manner concerning neurodegeneration especially Alzheimer's disease.

아플라톡신 B1은 표적 생물, 특히 인간에 대한 곰팡이 독소 중 가장 큰 위험을 초래하지만 아플라톡신의 만성 노출에 따른 신경 독성을 다룬 연구는 아직 없습니다. 세 가지 아플라톡신 그룹에 각각 음성 및 차량 대조군에 대해 30일, 60일, 90일 동안 LD50의 1/600 수준의 경구 투여량을 사용했습니다. 뇌 항산화 물질인 슈퍼옥사이드 디스뮤타아제, 카탈라아제, 글루타치온, 글루타치온 퍼옥시다아제의 활성도는 세 실험 기간 동안 시간 의존적 경향으로 유의하게 감소한 반면, 지질 과산화는 대조군에 비해 유의하게 증가했습니다. 산성 포스파타제(16.1%, 35.2%), 알칼리성 포스파타제(32.1%, 50.8%), 아스파테이트 아미노전달효소(38.7%, 120.0%), 젖산탈수소효소(30.6%, 42.1%) 활성은 AF60 및 AF90 그룹에서 각각 만성 의존적 증가 경향이 유의하게 관찰되었습니다. 그러나 90일 동안 AFB1을 투여한 후 뇌 크레아틴 키나아제 활성은 23.7% 유의하게 감소한 것으로 나타났습니다. 아플라톡신을 만성적으로 투여하면 단백질 카르보닐의 활성도 변화하여 90일 후 최대 2배까지 증가합니다. 또한 조직 병리학적 및 면역 조직 화학적 결과에서 AFB1에 대한 반응으로 높은 아교 섬유 산성 단백질 면역 염색에 의한 시간 관련 혈관 확장, 괴사 및 성상 세포 신경교 증이 확인되었습니다. 이러한 결과는 AFB1에 장기간 노출되면 신경 퇴화, 특히 알츠하이머병과 관련하여 기간 의존적인 방식으로 여러 가지 병리 생리학적 상황이 발생한다는 것을 유추할 수 있습니다.