Targeting Oxidative Stress in Thyroid Disorder: Therapeutic
Keywords:
N-acetylcysteine, thyroid disorders, oxidative stress, hyperthyroidism, Graves' disease, antioxidantsAbstract
Thyroid disorders, including hyperthyroidism, Graves' disease, Graves' ophthalmopathy, Hashimoto's thyroiditis, and hypothyroidism, are among the most prevalent endocrine diseases worldwide and are associated with substantial metabolic, cardiovascular, and immunological complications. Increasing evidence indicates that oxidative stress plays a pivotal role in their pathogenesis by promoting mitochondrial dysfunction, chronic inflammation, immune dysregulation, and cellular injury. Although conventional therapies effectively restore thyroid hormone homeostasis and relieve clinical symptoms, they do not directly address the underlying oxidative mechanisms involved in disease progression. Consequently, antioxidant-based adjunctive therapies have attracted growing research interest. N-Acetylcysteine (NAC), a well-established antioxidant and precursor of glutathione, exhibits multiple biological activities beyond free radical scavenging, including restoration of intracellular glutathione, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, inhibition of nuclear factor-kappa B (NF-κB)-mediated inflammation, preservation of mitochondrial function, and modulation of immune responses. This mini-review summarizes current evidence regarding the role of oxidative stress in thyroid physiology and thyroid disorders and discusses the molecular mechanisms through which NAC may confer therapeutic benefits. Preclinical studies consistently demonstrate that NAC attenuates oxidative damage, restores antioxidant defenses, and protects against hyperthyroidism-induced tissue injury, particularly in experimental cardiomyopathy. However, clinical evidence supporting its use in thyroid disorders remains limited, especially in autoimmune thyroid diseases. Future well-designed clinical trials are required to establish the efficacy, optimal dosage, treatment duration, and long-term safety of NAC. Overall, NAC represents a promising adjunctive strategy for targeting oxidative stress in thyroid disorders and warrants further translational investigation.
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