(Overproduction of ROS and RNS) 1 A number of xenobiotics can DIRECTLY GENERATE ROS and RNS, such as __ 2 Overproduction of ROS and RNS can be secondary to intracellular __ 3 Ca2+ helps generate ROS and/or RNS by activating __ in the citric acid cycle leading to increased activity in the electron transport chain and increased formation of O2 • and HOOH, and by activating nitric oxide synthase, which leads to formation of ONOO