Sophocarpine attenuates avermectin-induced kidney injury in carp through inhibiting inflammation and ferroptosis via regulating Nrf2/SLC7A11/GPX4 signaling pathway.

Avermectin (AVM), as one of the most important members of the biopesticide family, is widely used in the fields of agriculture and forestry production. An increasing number of reports indicate the toxic effects of avermectin in environmental exposure. Sophocarpine (SPC) is known to exhibit anti-inflammatory function. The effect of SPC on AVM-induced kidney injury in carp were investigated. The carps were received AVM for 30 days and SPC was given 1 h after AVM treatment. Then, kidney injury was tested by detecting kidney pathological change and myeloperoxidase (MPO) activity. Inflammatory cytokine production and signaling pathway were also detected. SPC significantly alleviated AVM-induced kidney histopathological changes and MPO activity. TNF-α and IL-1β production and nuclear factor kappa-B (NF-κB) activation were also inhibited by the treatment of SPC. Meanwhile, AVM-induced malondialdehyde (MDA) and Fe2+ contents were prevented by SPC. And SPC increased GPX4 and SLC7A11 expression, as well as GSH level decreased by AVM. Furthermore, SPC markedly increased nuclear factor erythroid-2 related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) expression. These results indicated SPC may have protective effects against AVM-induced kidney injury through inhibiting inflammation and ferroptosis via Nrf2/SLC7A11/GPX4 signal pathway.