drug minoxidil contains an NO moiety and may act as an NO agonist. The mechanism of action for sildenafil (Viagra) is closely related to NO signaling. Inhaled NO may improve survival and recovery from paraquat poisoning. Carbon monoxide Carbon monoxide (CO) is produced naturally throughout phylogenetic kingdoms. In mammalian physiology, CO is an important neurotransmitter with beneficial roles such as reducing inflammation and blood vessel relaxation. Mammals maintain a baseline carboxyhemoglobin level even if they do not breathe any CO fumes. In mammals, CO is produced through many enzymatic and non-enzymatic pathways. The most extensively studied source is the catabolic action of heme oxygenase (HMOX) which has been estimated to account for 86% of endogenous CO production. Other contributing sources include: the microbiome, cytochrome P450 reductase, human acireductone dioxygenase, tyrosinase, lipid peroxidation, alpha-keto acids, and other oxidative mechanisms. Similarly, the velocity and catalytic activity of HMOX can be enhanced by a plethora of dietary substances and xenobiotics to increase CO production. The biomedical study of CO traces back to factitious airs in the 1790s when Thomas Beddoes, James Watt, James Lind, and many others investigated beneficial effects of hydrocarbonate (water gas) inhalation. Following Solomon Snyder's first report that CO is a normal neurotransmitter in 1993, CO has received significant clinical attention as a biological regulator. Unlike NO and , CO is an inert molecule with remarkable chemical stability capable of diffusing through membranes to exert its effects locally and in distant tissues. CO has been shown to interact with molecular targets including soluble guanylyl cyclase, mitochondrial oxidases, catalase, nitric oxide synthase, mitogen-activated protein kinase, PPAR gamma, HIF1A, NRF2, ion channels, cystathionine beta synthase, and numerous other functionalities. It is widely accepted that CO primarily exerts its effects in mammals primarily through interacting with ferrous ion complexes such as the prosthetic heme moiety of hemoproteins. Aside from Fe2+ interactions, CO may also interact with zinc within metalloproteinases, non-metallic histidine residues of certain ion channels, and various other metallic targets such nickel and molybdenum. Studies involving carbon monoxide have been conducted in many laboratories throughout the world for its anti-inflammatory and cytoprotective properties. These properties have potential to be used to prevent the development of a series of pathological conditions including ischemia reperfusion injury, transplant rejection, atherosclerosis, severe sepsis, severe malaria, autoimmunity, and many other indications. Hydrogen sulfide Hydrogen sulfide () has important signaling functions in mammalian physiology. The gas is produced