Nitrite Enhances MC-LR-Induced Changes on Splenic Oxidation Resistance and Innate Immunity in Male Zebrafish

Abstract

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.

Effects of Microcystin-LR on the Microstructure and Inflammation-Related Factors of Jejunum in Mice

“…These activities may result in eutrophication and development of cyanobacterial blooms [1,2]. The monocyclic heptapeptide microcystins (MCs) are the secondary products of cyanobacteria metabolism and most harmful cyanotoxin found in water bodies [3,4,5]. More than 200 isomers of MCs have been identified from cyanobacterial blooms, with MC-LR being the most widely distributed, abundant and toxic [1,6,7].…”

Microcystin-Induced Immunotoxicity in Fishes: A Scoping Review

“…It is well known that fish largely rely on the nonspecific immune system, which is tightly linked to the oxidant-antioxidant balance of the immune organs. Our previous study demonstrated that 30 µg/L of pure MC-LR resulted in a significant decrease in splenic GSH content in zebrafish [111]. GSH could exert a detoxification effect by binding MCs to form MC-GSH conjugates, and the reduction in cytosol GSH implied an excessive ROS production [112,113].…”