TABLE 2.

The effects of CO and CORMs on COX

Study Reference	CO Source	Preparation	Effect
(Miró et al., 1998)	CO gas	Analysis of lymphocytes from acute CO poisoning patients	Inhibition by 76% at 17% of COHb
(Alonso et al., 2003)	CO gas	Incubation of isolated human muscle mitochondria with 50–500 ppm of CO	Inhibition level: 20%-55%
(D’Amico et al., 2006)	Dissolved CO	HEK293 cells were incubated with 5–20 μM CO solution.	CO gas solution incubation for 5 min: normoxic conditions = inhibition by 40% (20 μM CO); hypoxic conditions (1% oxygen) = inhibition by 75% (20 μM CO)
(D’Amico et al., 2006)	Induced HO-1	HO-1 expression was induced by tetracycline in HEK293 cells.	HO-1 induction: normoxic conditions = inhibition by 23%; hypoxic conditions (1% oxygen) = inhibition by 70%
(Almeida et al., 2012)	Dissolved CO	Isolated mitochondria from rat cerebral cortex and astrocytes were incubated with CO gas solution of various concentrations.	Incubation with CO gas solution led to a slight inhibition for a short term (first 5 min) and a long-term activation (up to 60 min in isolated mitochondria and 24 h in astrocytes).
(Queiroga et al., 2011)	Dissolved CO	Isolated mitochondria from mouse liver were treated with CO gas solution.	10 μM CO gas solution inhibited COX activity by 50% in the first 10 min and increased COX activity by 20% at 30 min.
(Zuckerbraun et al., 2007)	CO gas	RAW 267.4 cells were exposed to 250 ppm CO gas for 1 h.	COX activity was inhibited by 50%.
(Lo Iacono et al., 2011)	CORM-3	Isolated mitochondria from rat heart were incubated with CORM-3.	100 μM CORM-3 reduced the activity of COX by 50%. However, 20 μM CORM-3 did not show any effects.
(Yang et al., 2020a)	CORM-2	Human endothelial cells (EA.hy926) were incubated with 25 μM CORM-2.	COX activity was not directly measured. Cellular ROS production induced by CORM-2 was diminished by incubating with antimycin A.