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.
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.
['Zhang|Dong-Ming|DM|', 'Guo|Zhi-Xin|ZX|', 'Zhao|Yun-Long|YL|', 'Wang|Qiu-Ju|QJ|', 'Gao|Yong-Sheng|YS|', 'Yu|Ting|T|', 'Chen|Yu-Ke|YK|', 'Chen|Xiu-Mei|XM|', 'Wang|Gui-Qin|GQ|']
D000818:Animals D000893:Anti-Inflammatory Agents D000975:Antioxidants D002331:Carnitine D002352:Carrier Proteins D002460:Cell Line D003530:Cyprinidae D004305:Dose-Response Relationship, Drug D005393:Fish Diseases D005395:Fish Oils D029941:Fish Proteins D007249:Inflammation D051267:NF-E2-Related Factor 2 D016328:NF-kappa B D010084:Oxidation-Reduction D018384:Oxidative Stress D020011:Protective Agents D011897:Random Allocation D015398:Signal Transduction
L-carnitine Nrf2/Keap1 NF-κB Rhynchocypris lagowski Dybowski Oxidized fish oil