Table 1.

Summary of ROS-generating sources in the context of ED conditions.

ROS-Generating Sources	Function and Mechanism	Conditions	Clinical and Experimental Models
NADPH oxidase	- Generates ROS by transferring electrons from NADPH to O₂ [54] - Comprises cytosolic (p47phox, p67phox) and membrane (p22phox, gp91phox) components [55,56]	Diabetes Mellitus, Hypertension, Cigarette Smoking, Sickle Cell Disease, Hyperhomocysteinemia, Obesity, Psychological Stress [57]	- Diabetes (rats) [114,117,118], - Hypertension (rats) [123,124], - Smoking (mice) [142,143], - Sickle Cell Disease (mice) [172], - Hyperhomocysteinemia (rabbits) [164,165], - Psychological Stress (rats) [161], - Obesity (human) [88]
eNOS uncoupling	- NOS isoforms (eNOS, nNOS, iNOS) typically produce NO - Under pathological conditions, produce superoxide (uncoupling) [67]	Aging, Diabetes Mellitus, Hyperlipidemia, Sickle Cell Disease, Cigarette Smoking, Chronic Kidney Disease [75]	- Aging (rats) [90], - Diabetes (mice) [112,113], - Hyperlipidemia (mice) [129,130], - SCD (mice) [172], - Obesity (human) [88], - Smoking (mice) [142,143], - Chronic Kidney Disease (mice) [135]
Mitochondrial ROS	- Produced during oxidative phosphorylation [79] - ETC in inner mitochondrial membrane transfers electrons through complexes I–IV [80]	Diabetes Mellitus, Hyperlipidemia [84]	- Diabetes Mellitus (mice) [84] - Hyperlipidemia (rats) [134]
Xanthine oxidase	- Converts hypoxanthine to xanthine, then uric acid - Generates ROS (hydrogen peroxide, superoxides) [60,61]	Diabetes Mellitus, Hyperlipidemia, Sickle Cell Disease [64]	- Diabetes (rats) [64], - Hyperlipidemia (rats) [134], - Sickle Cell Disease (mice) [172]

ROS: reactive oxygen species, NADPH: nicotinamide adenine dinucleotide phosphate, eNOS: endothelial nitric oxide synthase, iNOS: inducible nitric oxide synthase, nNOS: neuronal nitric oxide synthase, ETC: electron transport chain.