Ethanol consumption increases the generation of ROS and decreases the antioxidant activity, leading to the increase of oxidative stress. Increased oxidative stress from ethanol exposure is a critical element for the pathogenesis of ALD [29]. Growing evidence suggests that the interaction between complement activation and oxidative stress plays crucial roles in ALD [29-31]. Under basal conditions, the anaphylatoxin C3a and C5a receptors are highly expressed in Kupffer cells. Ethanol-induced complement activation results in the generation of the anaphylatoxins C3a and C5a, which bind to the receptors on Kupffer cells, and subsequently increases the expression of inflammatory cytokines and releases the ROS, contributing to ALD [28]. However, the mechanisms underlying the interaction between complement activation and oxidative stress in ALD remain unclear. A recent study found that C3a and its degraded form, C3a-des-Arg (also known as acylation stimulating protein [Asp]), contribute to the pathogenesis of AFLD. Asp binding to its receptor C5aR2 promotes the expression of cytochrome P450 family 2, subfamily E, polypeptide 1, which induces the production of ROS. The induced oxidative stress subsequently leads to the increased expression of
