Microcystin-LR induces ferroptosis in intestine of common carp (Cyprinus carpio).

Abstract Previous studies provide comprehensive evidence of the environmental hazards and intestinal toxicity of microcystin-LR (MC-LR) exposure. However, little is known about the mechanisms underlying the injury of intestine exposed to MC-LR. Juvenile common carp (Cyprinus carpio) were exposed to MC-LR (0 and 10 μg/L) for 15 days. The results suggest that organic anion-transporting polypeptides 3a1, 4a1, 2b1, and 1d1 mediate MC-LR entry into intestinal tissues. Lesion morphological features (vacuolization, deformation and dilation of the endoplasmic reticulum [ER], absence of mitochondrial cristae in mid-intestine), up-regulated mRNA expressions of ER stress (eukaryotic translation initiation factor 2-alpha kinase 3, endoplasmic reticulum to nucleus signaling 1, activating transcription factor [ATF] 6, ATF4, DNA damage-inducible transcript 3), iron accumulation, and down-regulated activity of glutathione peroxidase (GPx) and glutathione (GSH) content were all typical characteristics of ferroptosis in intestinal tissue following MC-LR exposure. GSH levels in intestinal tissue corroborated as the most influential GSH/GPx 4- related metabolic pathway in response to MC-LR exposure. Verrucomicrobiota, Planctomycetes, Bdellovibrionota, Firmicutes and Cyanobacteria were correlated with the ferroptosis-related GSH following MC-LR exposure. These findings provide new perspectives of the ferroptosis mechanism of MC-LR-induced intestinal injury in the common carp.