N-Acetylcysteine and Atherosclerosis: Promises and Challenges

Abstract

Atherosclerosis remains a leading cause of cardiovascular diseases. Although the mechanism for atherosclerosis is complex and has not been fully understood, inflammation and oxidative stress play a critical role in the development and progression of atherosclerosis. N-acetylcysteine (NAC) has been used as a mucolytic agent and an antidote for acetaminophen overdose with a well-established safety profile. NAC has antioxidant and anti-inflammatory effects through multiple mechanisms, including an increase in the intracellular glutathione level and an attenuation of the nuclear factor kappa-B mediated production of inflammatory cytokines like tumor necrosis factor-alpha and interleukins. Numerous animal studies have demonstrated that NAC significantly decreases the development and progression of atherosclerosis. However, the data on the outcomes of clinical studies in patients with atherosclerosis have been limited and inconsistent. The purpose of this review is to summarize the data on the effect of NAC on atherosclerosis from both pre-clinical and clinical studies and discuss the potential mechanisms of action of NAC on atherosclerosis, as well as challenges in the field.

A Non-Coronary, Peripheral Arterial Atherosclerotic Disease (Carotid, Renal, Lower Limb) in Elderly Patients—A Review PART II—Pharmacological Approach for Management of Elderly Patients with Peripheral Atherosclerotic Lesions outside Coronary Territory

“…Antiplatelets and anticoagulants (aspirin, 2PY12 receptor inhibitors, cilostazol, rivaroxaban in a peripheral dose of 2.5 mg b.d., dipyridamole) do not reduce the thickness of atherosclerotic lesions; however, their effect is to limit thrombosis in ruptured atherosclerotic plaques and microvascular thrombosis, especially where collateral circulation is important, such as in PAD [ 38 ]. Natural antioxidants (curcumin, resveratrol, coenzyme Q10, bioflavonoids, lutein, β-carotene, vitamins A, E, and C, and the micronutrients selenium, zinc, manganese, magnesium, and many others) used as monotherapy do not show antiatherosclerotic effects [ 39 , 40 ]. On the other hand, in polytherapy, antiatherosclerotic effects and effects on the normalization of cardiovascular risk factors are small [ 41 ].…”

Reactive Carbonyl Species and Protein Lipoxidation in Atherogenesis

“…As reported by Salekeen et al [6], antioxidant vitamins, synthetic and natural antioxidants, plant-derived phenolics, phytochemicals, or fish lipids could prevent atherogenesis in animal models but were found to be inefficient in human clinical trials. N-acetyl cysteine (NAC), a precursor of GSH synthesis, may neutralize RCS via its antioxidant, anti-inflammatory, and RCS-scavenger properties [242]. NAC decreases atherosclerosis in animal models, but clinical studies in CVD patients provided limited or inconsistent results [242].…”

“…N-acetyl cysteine (NAC), a precursor of GSH synthesis, may neutralize RCS via its antioxidant, anti-inflammatory, and RCS-scavenger properties [242]. NAC decreases atherosclerosis in animal models, but clinical studies in CVD patients provided limited or inconsistent results [242]. In addition, antioxidants are unable to neutralize RCS bioreactivity once they are formed [11].…”