thiobarbituric-acid and Hyperthyroidism

To determine whether beta blockade protects against the acceleration of lipid peroxidation in hyperthyroid rat soleus (slow-oxidative) muscle, in vivo chronic (3 weeks) effects of 3 beta blockers with different ancillary properties on mitochondrial oxidative enzymes, antioxidant enzymes, and thiobarbituric acid-reactive substances were investigated. The rats were rendered hyperthyroid by the administration of thyroxine and treated simultaneously with either carteolol (a nonselective blocker with partial agonist activity; 30 mg/kg/day), atenolol (a beta 1-selective blocker; 50 mg/kg/day), or arotinolol (a nonselective blocker with weak alpha-blocking action; 50 mg/kg/day) over a 3 week period. Hyperthyroidism induced tachycardia, an increase in the mitochondrial oxidative enzymes, manganese (mitochondrial) superoxide dismutase and thiobarbituric acid-reactive substances, and a decrease in the other antioxidant enzymes. The tachycardia was alleviated completely by either atenolol or arotinolol, but partially by carteolol. Arotinolol, but neither carteolol nor atenolol, inhibited the increase in oxidative enzymes and thiobarbituric acid-reactive substances. The levels of antioxidant enzymes were minimally affected by the beta-blocker treatment. Beta 2-, and possibly alpha- as well, but not beta 1-, blockade suppressed mitochondrial hypermetabolism and protected against peroxidative injury in the hyperthyroid soleus muscle. Partial agonist activity was not beneficial.

Topics: Adrenergic beta-Antagonists; Animals; Atenolol; Body Weight; Carteolol; Hyperthyroidism; Lipid Peroxidation; Male; Mitochondria, Muscle; Muscles; Organ Size; Propanolamines; Rats; Rats, Inbred Strains; Thiobarbiturates

To determine whether beta-blockade protects rat heart against thyroxine (T4)-induced accelelation of lipid peroxidation, in vivo effects of 3 beta-blockers with different ancillary properties on the mitochondrial oxidative enzyme, antioxidant enzymes and lipid peroxide were investigated. The rats were rendered hyperthyroid by adding T4 to their drinking water for 3 weeks and were treated simultaneously with either carteolol (a blocker with partial agonist activity; 30 mg/kg/day), atenolol (50 mg/kg/day) or arotinolol (a blocker with weak alpha-blocking action; 50 mg/kg/day). The T4-induced tachycardia was alleviated completely by either atenolol or arotinolol, but only partially by carteolol. Cytochrome c oxidase activity in the heart muscle was increased by T4 with a parallel increase in manganese (mitochondrial) superoxide dismutase. Atenolol, but neither carteolol nor arotinolol, suppressed this increase. Similarly, the T4-induced acceleration of lipid peroxidation was suppressed by atenolol alone. Glutathione peroxidase was markedly decreased, and both copper zinc (cytosolic) superoxide dismutase and catalase were also decreased or tended to be decreased by T4. The levels of these 3 enzymes were only minimally affected by the beta-blocker treatments. These results suggest that beta-blockade suppresses mitochondrial hypermetabolism and protects heart muscle against oxidative stress in hyperthyroidism, and that the ancillary properties of beta-blockers such as partial agonist activity and alpha-blocking action negate the protection.

Topics: Adrenergic beta-Antagonists; Animals; Catalase; Electron Transport Complex IV; Glutathione Peroxidase; Heart; Hyperthyroidism; Lipid Peroxidation; Manganese; Rats; Rats, Inbred Strains; Superoxide Dismutase; Thiobarbiturates

The effect of hyper- and hypothyroidism on lipid peroxidation has been studied in rat liver microsomes under three different experimental conditions. Under none of these conditions was the formation of TBA-reactive substances affected by either of these two pathological states. On the contrary, with NADPH as the only peroxidation inducer, hydroperoxide concentration increased some three fold in microsomes from hyperthyroid rats, while a small decrease was measured in those from hypothyroid animals. Similarly, the activity of NADPH-cytochrome P-450 reductase was found to be 45.1% higher in hyperthyroid and 40.3% lower in hypothyroid microsomes. The possibility discussed here is that two distinct peroxidative mechanisms (of which one, NADPH-cytochrome P-450 reductase-dependent, is influenced by the thyroid hormone) can compete with each other for the substrate polyunsaturated fatty acids.

Topics: Animals; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Lipid Peroxides; Male; Microsomes, Liver; NADPH-Ferrihemoprotein Reductase; Rats; Rats, Inbred Strains; Thiobarbiturates