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Effects of beta-adrenergic blockers with different ancillary properties on lipid peroxidation in hyperthyroid rat
K Asayama1, K Dobashi, H Hayashibe
1Department of Pediatrics, Yamanashi Medical College, Japan.
Abstract:
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.
Insights
Beta-blockade can protect the heart from thyroxine-induced oxidative stress in rats. However, ancillary properties of beta-blockers may negate these protective effects against hyperthyroidism.
Area of Science:
- Cardiovascular Physiology
- Mitochondrial Biology
- Pharmacology
Background:
- Thyroid hormones, like thyroxine (T4), can induce hypermetabolism and oxidative stress in the heart.
- Beta-blockers are used to manage cardiovascular conditions, but their effects on T4-induced cardiac oxidative stress are not fully understood.
- Ancillary properties of beta-blockers may influence their therapeutic efficacy.
Purpose of the Study:
- To investigate the protective effects of beta-blockade against thyroxine (T4)-induced lipid peroxidation in the rat heart.
- To examine the in vivo effects of three beta-blockers with distinct ancillary properties on mitochondrial oxidative enzymes and antioxidant defenses.
- To determine if beta-blocker ancillary properties influence their cardioprotective actions in a hyperthyroid state.
Main Methods:
- Rats were rendered hyperthyroid using T4 administration for three weeks.
- Simultaneous treatment with carteolol, atenolol, or arotinolol was administered.
- Mitochondrial oxidative enzymes, antioxidant enzymes (glutathione peroxidase, superoxide dismutases, catalase), and lipid peroxide levels were assessed.
Main Results:
- T4 increased heart muscle cytochrome c oxidase activity and manganese superoxide dismutase, which was suppressed by atenolol but not other beta-blockers.
- T4-induced lipid peroxidation was suppressed by atenolol alone.
- Atenolol, carteolol, and arotinolol minimally affected the levels of glutathione peroxidase, copper-zinc superoxide dismutase, and catalase.
Conclusions:
- Beta-blockade can mitigate mitochondrial hypermetabolism and protect the heart from oxidative stress in hyperthyroidism.
- The ancillary properties of beta-blockers, such as partial agonist activity and alpha-blocking action, may diminish their cardioprotective effects.
- Atenolol demonstrated significant cardioprotective effects against T4-induced oxidative stress, likely due to its specific pharmacological profile.