L-carnitine regulated Nrf2/Keap1 activation in vitro and in vivo and protected oxidized fish oil-induced inflammation response by inhibiting the NF-κB signaling pathway in Rhynchocypris lagowski Dybowski

Abstract

Nrf2/Keap1 pathway is associated with oxidative stress. l-carnitine is currently under preclinical evaluation as a antioxidant, but the use of l-carnitine in aquaculture has been poorly evaluated and so far no mechanism has been demonstrated. Here, we explored the effects of l-carnitine in vitro and in vivo and discussed the possible molecular mechanisms involved. Firstly, Nrf2-siRNA significantly knocked down the mRNA level of Nrf2 in FHM cells. Thus, the activities of antioxidant enzymes (T-SOD, CAT, GSH-PX) and the level of antioxidant substance (GSH) and the level of MDA showed that Nrf2-siRNA pretreatment weakened the protective effect of l-carnitine. Moreover, the mRNA levels of Keap1, Nrf2, Maf and HO-1 indicated that l-carnitine regulated Nrf2/Keap1 activation. Furthermore, oxidized fish oil remarkably suppressed growth in Rhynchocypris lagowski Dybowski, and the lower antioxidant capacity was also observed in liver. According to the results of immune related indexes (the levels of IL-1β, TNF-α, LZM, AKP) in serum and the mRNA levels of immune related genes (NF-κB, IL-1β, TNF-α, IL-8, IL-10 and TGF-β) in liver, oxidized fish oil also induced inflammatory response in fish. Also, l-carnitine supplementation can relieve this bad condition. In conclusion, l-carnitine regulated Nrf2/Keap1 activation in vitro and in vivo and protected oxidized fish oil-induced inflammation response by inhibiting the NF-κB signaling pathway in Rhynchocypris lagowski Dybowski.

Keywords: L-carnitine; NF-κB; Nrf2/Keap1; Oxidized fish oil; Rhynchocypris lagowski Dybowski.