Abstract
Hyperthyroidism sensitizes the heart for reperfusion injury. As known, mitochondrial permeability transition underlies reperfusion heart damage. This study was undertaken to explore the protective effect of octylguanidine (OG), an inhibitor of permeability transition, on hearts from hyperthyroid rats subjected to ischemia/reperfusion. Hyperthyroidism was induced by a daily injection of 2 mg T3/kg body weight for 5 days. OG was injected at a dose of 5 mg/kg body weight. It was found that the amine protects against reperfusion-induced permeability transition, i.e., mitochondria from hyperthyroid rats, treated with OG, retained accumulated Ca2+, similarly to control mitochondria. OG maintained post reperfusion cardiac frequency in hyperthyroid rats at 429 ± 16 in comparison to control and T3 treated rats (70 ± 12 and 71 ± 2, respectively). We also found that OG diminished the post reperfusion accumulation of IFNγ from 34.3 ± 2.5 to 18.7 ± 1.35, IL-6 from 38.5 ± 4.5 to 15.1 ± 0.12, IL-1 from 16.78 ± 0.73 to 12.19 ± 1.54, and TNFα from 45.05 ± 3.14 to 29.85 ± 4.3 (pg/50 μg myocardial tissue). It is concluded that OG inhibits the hypersensitivity of the hyperthyroid myocardium to undergo reperfusion damage due to its inhibitory action on the permeability transition pore.
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Acknowledgment
The authors acknowledge the helpful expertise of Dr. Roberto Arreguín, from the Instituto de Química, UNAM, to verify the purity and mass of octylguanidine.
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Pavón, N., Aranda, A., García, N. et al. In hyperthyroid rats octylguanidine protects the heart from reperfusion damage. Endocr 35, 158–165 (2009). https://doi.org/10.1007/s12020-008-9144-0
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DOI: https://doi.org/10.1007/s12020-008-9144-0