Nicotinamide increases thyroid radiosensitivity by stimulating nitric oxide synthase expression and the generation of organic peroxides.
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.
Agote Robertson
M
M
División Bioquímica Nuclear, Departamento de Radiobiología, Comisión Nacional de Energía Atómica, Av. Del Libertador 8250, Buenos Aires 1429, Argentina.
Finochietto
P
P
Gamba
C A
CA
Dagrosa
M A
MA
Viaggi
M E
ME
Franco
M C
MC
Poderoso
J J
JJ
Juvenal
G J
GJ
Pisarev
M A
MA
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000528:radiation effects*; D006980:Hyperthyroidism / Q000150:complications / Q000532:radiotherapy; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D009536:Niacinamide / Q000008:administration & dosage*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D010084:Oxidation-Reduction / Q000187:drug effects / Q000528:radiation effects; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000201:enzymology* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000150:complications / Q000532:radiotherapy; D014803:Vitamin B Complex / Q000008:administration & dosage*
D007457:Iodine Radioisotopes; D010545:Peroxides; D014803:Vitamin B Complex; D009536:Niacinamide; D019001:Nitric Oxide Synthase