College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
Hubei Provincial Engineering Laboratory for Pond Aquaculture, Wuhan 430070, China.
Toxins (Basel). 2018 Dec 3;10(12):512. doi: 10.3390/toxins10120512.
Hazardous contaminants, such as nitrite and microcystin-leucine arginine (MC-LR), are released into water bodies during cyanobacterial blooms and may adversely influence the normal physiological function of hydrobiontes. The combined effects of nitrite and MC-LR on the antioxidant defense and innate immunity were evaluated through an orthogonal experimental design (nitrite: 0, 29, 290 μM; MC-LR: 0, 3, 30 nM). Remarkable increases in malondialdehyde (MDA) levels have suggested that nitrite and/or MC-LR exposures induce oxidative stress in fish spleen, which were indirectly confirmed by significant downregulations of total antioxidant capacity (T-AOC), glutathione (GSH) contents, as well as transcriptional levels of antioxidant enzyme genes cat1, sod1 and gpx1a. Simultaneously, nitrite and MC-LR significantly decreased serum complement C3 levels as well as the transcriptional levels of splenic c3b, lyz, il1β, ifnγ and tnfα, and indicated that they could jointly impact the innate immunity of fish. The severity and extent of splenic lesions were aggravated by increased concentration of nitrite or MC-LR and became more serious in combined groups. The damages of mitochondria and pseudopodia in splenic macrophages suggest that oxidative stress exerted by nitrite and MC-LR aimed at the membrane structure of immune cells and ultimately disrupted immune function. Our results clearly demonstrate that nitrite and MC-LR exert synergistic suppressive effects on fish innate immunity via interfering antioxidant responses, and their joint toxicity should not be underestimated in eutrophic lakes.
有害污染物，如亚硝酸盐和微囊藻氨酸-亮氨酸-精氨酸（MC-LR），在蓝藻水华期间会释放到水体中，可能会对水生生物的正常生理功能产生不利影响。通过正交实验设计（亚硝酸盐：0、29、290 μM；MC-LR：0、3、30 nM）评估了亚硝酸盐和 MC-LR 对抗氧化防御和先天免疫的联合作用。丙二醛（MDA）水平的显著升高表明，亚硝酸盐和/或 MC-LR 暴露会在鱼类脾脏中诱导氧化应激，这间接通过总抗氧化能力（T-AOC）、谷胱甘肽（GSH）含量以及抗氧化酶基因 cat1、 sod1 和 gpx1a 的转录水平的显著下调得到证实。同时，亚硝酸盐和 MC-LR 显著降低了血清补体 C3 水平以及脾脏 c3b、lyz、il1β、ifnγ 和 tnfα 的转录水平，表明它们可以共同影响鱼类的先天免疫。随着亚硝酸盐或 MC-LR 浓度的增加，脾脏病变的严重程度和范围加剧，联合组的情况更为严重。脾脏巨噬细胞中线粒体和伪足的损伤表明，亚硝酸盐和 MC-LR 产生的氧化应激作用于免疫细胞的膜结构，最终破坏了免疫功能。我们的研究结果清楚地表明，亚硝酸盐和 MC-LR 通过干扰抗氧化反应对鱼类先天免疫产生协同抑制作用，在富营养化湖泊中不应低估其联合毒性。
