Chlorine disinfection byproduct of diazepam affects nervous system function and possesses gender-related difference in zebrafish
Chlorinated disinfection byproducts in water posed potential health threat to humans. Nowadays, chlorinated derivatives of diazepam were ubiquitously detected in drinking water. Among these derivatives, 2-methylamino-5-chlorobenzophenone (MACB) was capable of penetrating the blood-brain barrier (BBB...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-06-01
|
| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322004080 |
| _version_ | 1818009409230471168 |
|---|---|
| author | Xiaole Zhao Xiaoyong Huang Wenjing Peng Muke Han Xin Zhang Kui Zhu Bing Shao |
| author_facet | Xiaole Zhao Xiaoyong Huang Wenjing Peng Muke Han Xin Zhang Kui Zhu Bing Shao |
| author_sort | Xiaole Zhao |
| collection | DOAJ |
| description | Chlorinated disinfection byproducts in water posed potential health threat to humans. Nowadays, chlorinated derivatives of diazepam were ubiquitously detected in drinking water. Among these derivatives, 2-methylamino-5-chlorobenzophenone (MACB) was capable of penetrating the blood-brain barrier (BBB) and induced microglial phagocytosis of neurons in zebrafish. However, little is known about the MACB metabolism in vivo. Here, we determined the metabolism of MACB in zebrafish and microglia cell model. We found that MACB mainly disrupted the metabolism of branched-chain amino acids (Leu, Ile and Val) in zebrafish model and gamma-aminobutyric acid (GABA) pathway-related amino acids in microglia model. Additionally, we demonstrated that MACB can be metabolized by the mixed-function oxidase CYP1A2 enzyme which could be inhibited by estrogen causing the gender-difference in the accumulation of MACB in vivo. These results indicated that MACB perturbed metabolism and induced neurological disorders, particularly in the female zebrafish. |
| first_indexed | 2024-04-14T05:42:29Z |
| format | Article |
| id | doaj.art-d05236125e554979bb7ead5de1b7acaa |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-14T05:42:29Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-d05236125e554979bb7ead5de1b7acaa2022-12-22T02:09:24ZengElsevierEcotoxicology and Environmental Safety0147-65132022-06-01238113568Chlorine disinfection byproduct of diazepam affects nervous system function and possesses gender-related difference in zebrafishXiaole Zhao0Xiaoyong Huang1Wenjing Peng2Muke Han3Xin Zhang4Kui Zhu5Bing Shao6College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, People’s Republic of China; Institute of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, People’s Republic of ChinaCollege of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, People’s Republic of China; Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing 100013, People’s Republic of ChinaCollege of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, People’s Republic of ChinaBeijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing 100013, People’s Republic of ChinaBeijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing 100013, People’s Republic of ChinaCollege of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, People’s Republic of China; Correspondence to: No.2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People’s Republic of China.College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, People’s Republic of China; Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing 100013, People’s Republic of China; Correspondence to: No.16 Hepingli middle street, Dongcheng District, Beijing 100013, People’s Republic of China.Chlorinated disinfection byproducts in water posed potential health threat to humans. Nowadays, chlorinated derivatives of diazepam were ubiquitously detected in drinking water. Among these derivatives, 2-methylamino-5-chlorobenzophenone (MACB) was capable of penetrating the blood-brain barrier (BBB) and induced microglial phagocytosis of neurons in zebrafish. However, little is known about the MACB metabolism in vivo. Here, we determined the metabolism of MACB in zebrafish and microglia cell model. We found that MACB mainly disrupted the metabolism of branched-chain amino acids (Leu, Ile and Val) in zebrafish model and gamma-aminobutyric acid (GABA) pathway-related amino acids in microglia model. Additionally, we demonstrated that MACB can be metabolized by the mixed-function oxidase CYP1A2 enzyme which could be inhibited by estrogen causing the gender-difference in the accumulation of MACB in vivo. These results indicated that MACB perturbed metabolism and induced neurological disorders, particularly in the female zebrafish.http://www.sciencedirect.com/science/article/pii/S01476513220040802-methylamino-5-chlorobenzophenoneZebrafishGender-related differenceCYP1A2 |
| spellingShingle | Xiaole Zhao Xiaoyong Huang Wenjing Peng Muke Han Xin Zhang Kui Zhu Bing Shao Chlorine disinfection byproduct of diazepam affects nervous system function and possesses gender-related difference in zebrafish Ecotoxicology and Environmental Safety 2-methylamino-5-chlorobenzophenone Zebrafish Gender-related difference CYP1A2 |
| title | Chlorine disinfection byproduct of diazepam affects nervous system function and possesses gender-related difference in zebrafish |
| title_full | Chlorine disinfection byproduct of diazepam affects nervous system function and possesses gender-related difference in zebrafish |
| title_fullStr | Chlorine disinfection byproduct of diazepam affects nervous system function and possesses gender-related difference in zebrafish |
| title_full_unstemmed | Chlorine disinfection byproduct of diazepam affects nervous system function and possesses gender-related difference in zebrafish |
| title_short | Chlorine disinfection byproduct of diazepam affects nervous system function and possesses gender-related difference in zebrafish |
| title_sort | chlorine disinfection byproduct of diazepam affects nervous system function and possesses gender related difference in zebrafish |
| topic | 2-methylamino-5-chlorobenzophenone Zebrafish Gender-related difference CYP1A2 |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322004080 |
| work_keys_str_mv | AT xiaolezhao chlorinedisinfectionbyproductofdiazepamaffectsnervoussystemfunctionandpossessesgenderrelateddifferenceinzebrafish AT xiaoyonghuang chlorinedisinfectionbyproductofdiazepamaffectsnervoussystemfunctionandpossessesgenderrelateddifferenceinzebrafish AT wenjingpeng chlorinedisinfectionbyproductofdiazepamaffectsnervoussystemfunctionandpossessesgenderrelateddifferenceinzebrafish AT mukehan chlorinedisinfectionbyproductofdiazepamaffectsnervoussystemfunctionandpossessesgenderrelateddifferenceinzebrafish AT xinzhang chlorinedisinfectionbyproductofdiazepamaffectsnervoussystemfunctionandpossessesgenderrelateddifferenceinzebrafish AT kuizhu chlorinedisinfectionbyproductofdiazepamaffectsnervoussystemfunctionandpossessesgenderrelateddifferenceinzebrafish AT bingshao chlorinedisinfectionbyproductofdiazepamaffectsnervoussystemfunctionandpossessesgenderrelateddifferenceinzebrafish |