Treatment with the nitric oxide donor SNP increases triiodothyronine levels in hyper- and hypothyroid Sprague-Dawley rats.

Nitric oxide pathway might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of nitric oxide (NO) on hypothyroid and hyperthyroid Sprague-Dawley rats under controlled diet. Furthermore, the effects of the nitric oxide donor sodium nitroprusside (SNP) on thyroid dysfunctions were also assessed. Sprague-Dawley rats (n=107) were subdivided into normal diet and high-fat diet (HFD) groups and grouped into controls, hypothyroid, hyperthyroid, and SNP treated groups. Hypothyroidism was induced through propylthiouracil, whereas hyperthyroidism by triiodothyronine (T3). After 12 weeks of T3 treatment, serum nitric oxides (NOX), endogenous asymmetric dimethylarginine (ADMA), body weight and food intake were analyzed. Hypothyroid rats showed decreased serum T3 levels, hyperthyroid rats increased T3 compared to controls. Diet had no impact on T3. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight. Serum NOX was significantly reduced in normal diet hypothyroid rats. SNP administration compensated the decrease and markedly increased T3. NO synthase inhibitor ADMA levels were significantly higher in the HFD control group than in the normal diet controls. ADMA was declined in both hypothyroid groups and increased in normal diet hyperthyroid rats. An association of thyroid dysfunctions with reduced bioavailability of NO and alterations of ADMA levels could be established. Treatment with the NO donor SNP resulted in an increase of serum T3 levels. These results demonstrate that the NO pathway is implicated in thyroid dysfunctions, which may be of clinical relevance.

Reduced urinary glutamate levels are associated with the frequency of migraine attacks in females.

BACKGROUND AND PURPOSE: Recent evidences indicate that glutamatergic homeostasis disorders are implicated in the pathogenesis of migraine. In particular, plasma and cerebrospinal fluid glutamate levels seem to be altered in migraine patients. However, the impacts of glutamate on migraine and especially on aura symptoms, alterations in the frequency of migraine attacks as well as investigations on glutamate on migraine-related metabolic dysfunctions, like hyperinsulinaemia, and an atherogenic lipid profile remain elusive to date. The aim of the present study was to investigate the impact of glutamate on migraine and related metabolic dysfunctions. METHODS: We investigated the urinary glutamate levels of female migraineurs (n = 48) in the interictal phase and healthy controls (n = 48). Parameters of the insulin- and lipid metabolism, inflammatory parameters and anthropometric parameters were additionally determined. RESULTS: Urinary glutamate levels of female migraineurs were significantly decreased with respect to the control group. Logistic regression revealed an odds ratio of 4.04 for migraine. We found a significant correlation with the time-period of patients' last attack and a significant inverse correlation with the annual frequency of migraine attacks. Other parameters of the insulin- and lipid metabolism, anthropometric and inflammatory parameters showed no significant correlation with glutamate levels. CONCLUSION: We show here that female migraineurs exhibit decreased urinary glutamate levels which are associated with a 4.04-fold higher risk for migraine and correlated with patients' frequency of migraine attacks.

Oxidative stress is associated with migraine and migraine-related metabolic risk in females.

BACKGROUND AND PURPOSE: Oxidative stress is discussed to be implicated in the pathophysiology of migraine. However, data are in part controversial and the possible underlying mechanisms remain elusive to date. The aim of this study was to investigate the oxidative stress status of female patients with migraine and its implications on migraine-related metabolic alterations. METHODS: Oxidative stress markers malondialdehyde (MDA), 4-hydroxy-2-nonenal (HNE), carbonylated proteins, parameters of associated nitric oxide stress, inflammation, lipid- and glucose-metabolism were determined in the interictal phase in female patients with migraine and controls. RESULTS: We found significantly increased HNE levels in female migraineurs compared with controls. Logistic regression analyses of HNE revealed an odds ratio for migraine of 4.55. HNE showed significant correlations with the nitric oxide pathway, the insulin- and the lipid-metabolism. CONCLUSIONS: We show here that increased oxidative stress is associated with migraine and contributes to migraine-related metabolic risk like nitrosative stress, an atherogenic lipid profile and hyperinsulinemia. Our data suggest that oxidative stress may represent a key event in the pathophysiology of migraine and a suitable therapeutic target.