Ferulic acid alleviates long-term avermectin-induced damage to the spleen of carp and restores its inflammatory response and oxidative balance.

Extensive use of avermectin (AVM) in agriculture can seriously contaminate fish in aquaculture. Ferulic acid (FA) is a strong antioxidant sourced from plants and is widely applied in food and medicine, but its protective function on the immunological damage caused by AVM is still lacking. In this study, carp were chronically exposed to (1/10 96 hr LC) AVM for 30 day(s), with a dietary supplement of FA (400 mg/kg) to assess its effects on carp spleen. The experimental groups (n = 10) included: control, AVM-exposed (2.404 µg/L), FA + AVM co-treated, and FA alone. Long-term AVM exposure altered spleen tissue, reducing serum complement C3 (p < 0.01) and immunoglobulin M levels (p < 0.001), and increasing pro-inflammatory tnf-α (p < 0.001), il-6 (p < 0.001), il-1β (p < 0.001), and inos mRNA levels, whilst down-regulating the anti-inflammatory tgf-β (p < 0.05). Additionally, it disrupted the balance of oxidative stress indicators such as MDA (p < 0.001), T-AOC, GSH, and CAT, leading to spleen tissue apoptosis (42.4%). However, the addition of FA reversed these conditions, elevated the anti-inflammatory factor, and improved spleen immune function following chronic exposure to AVM in carp. Moreover, the ability to restore oxidative homeostasis in carp by adjusting the Nrf2/NQO-1 axis protected the health of spleen tissues. This discovery also supports the development of fish feed for aquaculture.