Persistent Exposure to Environmental Levels of Microcystin-LR Disturbs Cortisol Production via Hypothalamic-Pituitary-Interrenal (HPI) Axis and Subsequently Liver Glucose Metabolism in Adult Male Zebrafish (Danio rerio).

Lingkai Wang,Wang Lin,Liping Yang,Dandan Zhang,Honghui Guo,Qingji Zha,Rong Tang,Dapeng Li,Li Li

doi:10.3390/toxins12050282

Abstract

There is growing evidence that microcystin-LR (MC-LR) is a new endocrine disruptor, whereas the impacts of persistent exposure to MC-LR on the hypothalamic-pituitary-interrenal (HPI) axis and health hazards thereafter have not been investigated. In this work, adult male zebrafish (Danio rerio) were immersed into MC-LR solutions at concentrations of 0, 1, 5 and 25 μg/L for 30 d, respectively. The results showed that persistent MC-LR exposure caused an extensive upregulation of HPI-axis genes but an inhibition of brain nuclear receptors (gr and mr), which finally increased serum cortisol levels. Furthermore, the decreased expression of hepatic gr might partly be responsible for the strong inhibition on the expression of downstream genes involved in glucose metabolic enzymes, including gluconeogenesis-related genes (pepck, fbp1a, g6pca), glycogenolysis-related gene (pyg), glycolysis-related genes (gk, pfk1b, pk) and glycogenesis-related gene (gys2). These findings are in accordance with the decline in serum glucose, indicating that long-term MC-LR exposure caused a lower production of glucose relative to glucose lysis. Our above results firstly establish the link between persistent MC-LR exposure and impaired glucose metabolism, suggesting that long-term MC-LR-mediated stress might threaten fish’s health.

Highlights

Due to water eutrophication and global warming, the high frequencies of cyanobacterial blooms have attracted growing interest in recent decades [1,2,3]
1, serum cortisol shown in Figure serum cortisol group levels were increased in 5 and
This present study firstly revealed that persistent exposure to environmental levels of MC-LR interferes with interrenal cortisol production via modulating the expression of HPI-axis genes, which subsequently impaired hepatic glucose metabolism and posed a threat to fish’s health

Summary

Introduction

Due to water eutrophication and global warming, the high frequencies of cyanobacterial blooms have attracted growing interest in recent decades [1,2,3]. Microcystins (MCs), a group of cyclic peptides with seven amino acids, are the most commonly detected cyanotoxins in freshwater blooms. Microcystin-LR (MC-LR) is the most widely distributed, abundant and toxic among these congeners [5]. The level of 1 μg/L MC-LR is recommended as the standard concentration in drinking water by the World Health Organization [6]. The real concentration of dissolved MC-LR in natural water is in the range of 0.1–10 μg/L, which generally oversteps the recommended level and causes potential harm to aquatic animals and human beings [7,8]

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