Department of Physiology and Pharmacology, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brazil.
LEEM-Laboratory of Ecophysiology and Molecular Evolution, Brazilian National Institute for Research of the Amazon, Manaus, Amazonas, Brazil.
Fish Physiol Biochem. 2020 Dec;46(6):2055-2064. doi: 10.1007/s10695-020-00854-0. Epub 2020 Aug 7.
The practice of replacing costly animal-derived proteins with more economical plant proteins has augmented the risk of mycotoxin contamination in fish feeds, including contamination with ochratoxin A (OTA). OTA is a secondary metabolite produced by molds commonly found in fish feeds that causes impairment of performance in several fish species and some hepatic biochemical alterations. However, the pathways involved in hepatic damage remain unknown and are limited to histopathological alterations. Purinergic signaling is a homeostatic system that continuously monitors the internal environment to detect injury primarily by two intercellular messengers: adenosine triphosphate (ATP) and adenosine (Ado). The objective of this study was to determine whether OTA-contaminated feed induces the release of nucleotides in the extracellular milieu, as well as whether ectoenzymes modulate ATP pro-inflammatory effects in liver of tambaqui (Colossoma macropomum). Final mean weight, weight gain (WG), and liver weight were significantly lower in tambaqui fed feeds containing 1.6 and 2.4 mg OTA/kg feed than in the control group. Liver ATP and Ado levels were significantly higher in tambaqui fed feeds containing 1.6 and 2.4 mg OTA/kg feed compared with control, while no significant difference was observed regarding adenosine diphosphate and adenosine monophosphate levels. Hepatic triphosphate diphosphohydrolase (NTPDase) activity (for ATP) was significantly greater in tambaqui fed feeds containing 1.6 and 2.4 mg OTA/kg feed compared with control, while adenosine deaminase (ADA) activity was lower. No significant difference was observed with respect to hepatic NTPDase activity (for ADP) or for 5'-nucleotidase activity. Finally, levels of liver metabolites of nitric oxide were significantly higher in tambaqui fed feeds containing 1.6 and 2.4 mg OTA/kg feed than in the control group. Based on these data, exposure to 1.6 and 2.4 mg OTA/kg feed impaired tambaqui growth performance associated with final mean weight and WG. Levels of two important intercellular messengers, ATP and Ado, increased in the extracellular space as a consequence of hepatic damage, exerting opposite immune responses. Finally, liver NTPDase and ADA activities were altered to modulate ATP and Ado levels, respectively, exerting anti-inflammatory effects to counteract OTA-induced hepatic injury.
用更经济的植物蛋白替代昂贵的动物源性蛋白的做法增加了鱼类饲料中霉菌毒素污染的风险，包括赭曲霉毒素 A (OTA) 的污染。OTA 是一种常见于鱼类饲料中的霉菌产生的次级代谢物，会导致多种鱼类的性能受损，并导致一些肝生化改变。然而，肝损伤的途径仍不清楚，仅限于组织病理学改变。嘌呤能信号是一种持续监测内部环境以检测损伤的内稳态系统，主要通过两种细胞间信使：三磷酸腺苷 (ATP) 和腺苷 (Ado)。本研究的目的是确定 OTA 污染的饲料是否会在细胞外环境中释放核苷酸，以及外切酶是否会调节肝中的 ATP 促炎作用 tambaqui (Colossoma macropomum)。在喂食含有 1.6 和 2.4 mg OTA/kg 饲料的 tambaqui 中，终均重、增重 (WG) 和肝重明显低于对照组。与对照组相比，喂食含有 1.6 和 2.4 mg OTA/kg 饲料的 tambaqui 中肝 ATP 和 Ado 水平显著升高，而二磷酸腺苷和一磷酸腺苷水平无显著差异。肝三磷酸二磷酸水解酶 (NTPDase) 活性 (用于 ATP) 在喂食含有 1.6 和 2.4 mg OTA/kg 饲料的 tambaqui 中明显高于对照组，而腺苷脱氨酶 (ADA) 活性降低。肝 NTPDase 活性 (用于 ADP) 或 5'-核苷酸酶活性无显著差异。最后，喂食含有 1.6 和 2.4 mg OTA/kg 饲料的 tambaqui 中肝代谢物的一氧化氮水平明显高于对照组。基于这些数据，暴露于 1.6 和 2.4 mg OTA/kg 饲料会损害 tambaqui 的生长性能，与终均重和 WG 有关。两种重要的细胞间信使，ATP 和 Ado 的水平在细胞外空间增加，这是肝损伤的结果，产生相反的免疫反应。最后，肝 NTPDase 和 ADA 活性发生改变，分别调节 ATP 和 Ado 水平，发挥抗炎作用以抵消 OTA 诱导的肝损伤。
