The role of allopurinol on oxidative stress in experimental hyperthyroidism.
OBJECTIVE
During hyperthyroidism, production of free oxygen radicals derives, where xanthine oxidase may also play an important role. Allopurinol, a xanthine oxidase inhibitor, has a significant effect on thyrotoxicosis-related oxidative stress. However, the relationship between thyroid hormones, oxidative stress parameters and allopurinol remains to be explored.


METHODS
Forty-two Wistar albino rats were divided into three groups. Rats in group A served as negative controls, while group B had untreated thyrotoxicosis and group C received allopurinol. Hyperthyroidism was induced by daily 0.2 mg/kg L-thyroxine intraperitoneally in groups B and C; 40 mg/kg allopurinol were given daily intraperitoneally. Efficacy of the treatment was assessed after 72 h and 21 days, by measuring serum xanthine oxidase (XO), malondialdehyde (MDA), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx) and nitric oxide derivates (NO*x).


RESULTS
In both time periods, serum XO, MDA, GSH and NO*x levels were significantly increased after thyroid hormone induction (p<0.05). Levels of XO, MDA and NO*x decreased with allopurinol treatment (p<0.05). There was a remarkable decrease in triiodothyronine levels in group C after 72 h (p<0.05), and in both triiodothyronine and thyroxine levels in group C after 21 days (p<0.05). There was no difference between groups B and C in means of serum GSH, GR and GPx levels (p>0.05).


CONCLUSIONS
This study suggests an association between allopurinol and the biosynthesis of thyroid hormones. Allopurinol prevents the hyperthyroid state, which is mediated predominantly by triiodothyronine and not by XO. This issue has to be questioned in further studies where allopurinol is administered in control subjects.
Makay
O
O
Department of General Surgery, Ege University School of Medicine, 35100 Bornova, Izmir, Turkey. ozer.makay@ege.edu.tr
Yenisey
C
C
Icoz
G
G
Genc Simsek
N
N
Ozgen
G
G
Akyildiz
M
M
Yetkin
E
E
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D005980:Glutathione Reductase / Q000097:blood; D006980:Hyperthyroidism / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine; D014969:Xanthine Oxidase / Q000097:blood
D009569:Nitric Oxide; D008315:Malondialdehyde; D000493:Allopurinol; D005979:Glutathione Peroxidase; D014969:Xanthine Oxidase; D005980:Glutathione Reductase; D005978:Glutathione; D013974:Thyroxine