Increased CO<sub>2</sub> Concentration Mitigates the Impact of Nitrite on Zebrafish (<i>Danio rerio</i>) Liver and Gills
Nitrite and carbon dioxide (CO<sub>2</sub>) are common environmental substances in intensive aquaculture ponds. However, the effects and mechanisms of their combined exposure on aquatic animals remain unclear. In this study, we investigated the toxic effects of 2.5, 5, and 10 mg/L CO<...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
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| Series: | Fishes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2410-3888/10/5/205 |
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| Summary: | Nitrite and carbon dioxide (CO<sub>2</sub>) are common environmental substances in intensive aquaculture ponds. However, the effects and mechanisms of their combined exposure on aquatic animals remain unclear. In this study, we investigated the toxic effects of 2.5, 5, and 10 mg/L CO<sub>2</sub> in the presence of 2 mg/L nitrite on hematological, blood gas parameters, and liver physiological and pathological changes in zebrafish (<i>Danio rerio</i>) over 14 days and 28 days. Our results demonstrated a reduced nitrite uptake and accumulation in the gills and liver of zebrafish exposed to nitrite and varying levels of CO<sub>2</sub>. Increased CO<sub>2</sub> levels also led to a decrease in the expression of gill <i>ae1</i>, whereas the transcriptional levels of <i>nhe1</i> and <i>nhe3b</i>, <i>nkcc</i> and <i>nbc1</i> were notably upregulated. Moreover, there was a decrease in Cl<sup>−</sup> and Na<sup>+</sup> concentrations, along with an increase in K<sup>+</sup> concentrations. These changes suggested that zebrafish responded to increased CO<sub>2</sub> stress by reducing their absorption of chloride-dependent nitrite, excreting H<sup>+</sup> and maintaining their internal pH. Exposure to higher CO<sub>2</sub> levels in the presence of nitrite resulted in lower blood MetHb levels and liver oxidative stress compared to the nitrite single-exposure treatment. Furthermore, co-treatment with CO<sub>2</sub> and nitrite attenuated the nitrite-induced damage to genes related to mitochondrial respiratory chain function (<i>ndufs1</i>, <i>mtnd5</i>, <i>mtycb</i>, <i>atp5f1b</i>, <i>mtatp8</i>), leading to elevated ATP levels. Exposure to nitrite alone increased the expression of lipolytic genes (<i>hsla</i>, <i>cpt1aa</i>, <i>atgl</i>) and decreased the expression of lipid synthesis genes (<i>fasn</i>, <i>acaca</i>), resulting in a decrease in TG and TC content in zebrafish liver. However, co-treatment with CO<sub>2</sub> and nitrite prevented the nitrite-induced disruption of lipid metabolism, as evidenced by the improvement in TG and TC levels, as well as transcriptional levels of lipid metabolism-related genes. In conclusion, our study suggests that in the presence of 2 mg/L nitrite, increased CO<sub>2</sub> (2.5–10 mg/L) may modulate ion transporter genes to reduce the chloride-dependent nitrite uptake and maintain pH homeostasis, concurrently alleviating oxidative stress, restoring mitochondrial respiratory function, and improving lipid metabolism in a dose-dependent manner. These changes may be related to the increase in the concentration of bicarbonate ions in the water as the CO<sub>2</sub> level rises. These findings shed light on the potential protective effects of CO<sub>2</sub> in mitigating the harmful effects of nitrite exposure in aquatic animals. |
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| ISSN: | 2410-3888 |