Nicotinamide Increases Thyroid Radiosensitivity by Stimulating Nitric Oxide Synthase Expression and the Generation of Organic Peroxides

Abstract

Differentiated thyroid cancer and hyperthyroidism are treated with radioiodine. However, when the radioisotope dose exceeds certain limits, the patient must be hospitalized to avoid contact with people that would otherwise be exposed to radiation. It would be desirable to obtain a similar therapeutic effect using lower radioiodine doses. Radiosensitizers can be utilized for this purpose. Nicotinamide (NA) increases thyroid radiosensitivity to 131I in both normal and goitrous glands. NA causes a significant increase in thyroid blood flow, which would increase tissue oxygenation and tissue damage via free radicals. Wistar rats were treated with either nicotinamide (NA), 131I or both. The expression of the three isoforms of nitric oxide synthase (NOS) in the thyroid (Western blot) and the activities of SOD, GPx, catalase and organic peroxides were determined. Treatment with NA or 131I increased the expression of eNOS and the generation of organic peroxides. When administered jointly, they showed a synergistic effect. No changes were observed in the other NOS isoforms or in the activities of catalase, glutathione peroxidase and superoxide dismutase. NA potentiates the effect of 131I by increasing eNOS, which would in turn stimulate NO production, increasing thyroid blood flow and tissue damage via organic peroxides.

Nicotinamide and its metaboliteN-methylnicotinamide increase skin vascular permeability in rats

“…It has been previously shown that nicotinamide inhibits the inducible NOS enzyme activity in macrophages, allowing NO to inhibit its own formation 25 . There are recent reports showing that nicotinamide increases endogenous NOS, which would in turn stimulate NO production, increasing thyroid blood flow 26 . It is unlikely however, that any NO‐mediated actions of the agents studied were dependent on DNA synthesis in our study because of the short time‐frame.…”

“…25 There are recent reports showing that nicotinamide increases endogenous NOS, which would in turn stimulate NO production, increasing thyroid blood flow. 26 It is unlikely however, that any NOmediated actions of the agents studied were dependent on DNA synthesis in our study because of the short time-frame. As nicotinamide possesses antioxidant properties, 27 it might be related instead to the enhancement of NO bioavailability.…”

Asymmetric Dimethylarginine (ADMA) and other Endogenous Nitric Oxide Synthase (NOS) Inhibitors as an Important Cause of Vascular Insulin Resistance

“…It is a guanidine-substituted analogue of L-arginine and acts as a potent endogenous competitive inhibitor of all isoforms of nitric oxide synthase (NOS): neuronal (n) NOS, inducible (i) NOS, and endothelial (e) NOS [23,24] . Nitric oxide (NO), the most widely studied endothelium-derived molecule, exerts potent vasodilatory, antiplatelet, anti-infl ammatory, antiproliferative / antitumor and antioxidant eff ects [25] . Because of these functions, NO has been characterized as an endogenous anti-atherosclerotic molecule [26] .…”

Modulation of the formation of active forms of nitrogen by ingredients of plant products in the inhibition of carcinogenesis

“…В условиях in vitro никотинамид выраженно снижал продукцию NO в культуре эндокринных клеток поджелудочной железы человека или мышиных макрофагов частично восстанавливая инсулиновую функцию клеток железы [130]. Однако у крыс никотинамид по вышает радиочувствительность щитовидной железы к йоду-131 за счет усиления экспрессии eNOS, увеличения кровотока и повреждения ткани органическими пероксидами [131].…”