Active oxygen species are reported to cause organ damage. This study was therefore designed to determine the behaviour of antioxidants and free radical scavengers so as to reveal changes in animals in the hyper- and hypothyroid state. Levels of antioxidant factors (i.e. coenzyme Q (CoQ)10, CoQ9 and vitamin E) and free radical scavengers (catalase, glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD)) were measured in the heart muscles of rats rendered hyper- or hypothyroid by 4 weeks of thyroxine (T4) or methimazol treatment. Serum levels of CoQ9 and total SOD were also measured. A significant reduction in CoQ9 levels was observed in the heart muscles of both hyper- and hypothyroid rats when compared with control hearts. There was no difference in serum CoQ9 levels in thyroid dysfunction when compared with control animals. Levels of vitamin E in the heart muscles of hyperthyroid rats were significantly increased, and there was no reduction in vitamin E levels in hypothyroid rats when compared with control hearts. GSH-PX levels in the heart muscle were reduced in hyperthyroid rats and increased in hypothyroid rats when compared with control hearts. However, there were no differences in catalase levels in heart muscle between hyper- and hypothyroid rats. The concentration of SOD in heart muscle was increased in hyperthyroid rats and was not decreased in hypothyroid rats compared with control rats, suggesting the induction of SOD by excessive production of O2-. These data suggest that the changes in these scavengers have some role in cardiac dysfunction in the hyper- and hypothyroid state in the rat.
Responses of hepatic afferent nerves to intraportal bolus injection of hypertonic solutions were examined in anesthetized rats. Hepatic afferent nerve activity increased in response to an intraportal injection of 0.75 M NaCl or NaHCO3 but did not respond to a similar injection of 1.5 M mannitol, 0.75 M LiCl, or 0.15 M NaCl, implying that nerves in the hepatoportal area are sensitive to increases in Na concentrations and that this leads to stimulation of hepatic afferent nerve activity. To study central activation in response to stimulation of the hepatic Na-sensitive mechanism, c-fos induction was monitored. After electrical stimulation of hepatic afferent nerves, neurons containing Fos-like immunoreactivity (Fos-li) were found in the area postrema, nucleus of the solitary tract, paraventricular hypothalamic nucleus, and supraoptic nucleus at 90 min after stimulation. Induction of Fos-li was also studied after simultaneous infusion of 0.45 M NaCl into the portal vein and distilled water into the inferior vena cava in conscious rats so as to keep the total amount of solution introduced into the systemic circulation isotonic, thus avoiding changes in mean arterial pressure, plasma osmolality, and plasma NaCl concentrations. Fos-li-containing neurons were found in the same regions in which they were found after electrical stimulation. However, few, if any, Fos-li-containing cells were found if the rats were hepatically denervated or if they received an intraportal infusion of hypertonic LiCl or mannitol. These data provide evidence for involvement of the brain stem and forebrain structures in NaCl regulatory functions induced by stimulation of the hepatoportal Na-sensitive mechanism. However, stimulation of the hepatoportal osmosensitive mechanism does not activate these central structures.
To determine how lipid peroxides and free radical scavengers are changed in the brain of hyper- or hypothyroid rats, we examined the behavior of lipid peroxide and free radical scavengers in the cerebral cortex of aged (1.5 years old) rats that had been made hyper- or hypothyroid by the administration of thyroxine or methimazol for 4 weeks. Concentrations of catalase, Mn-superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased in hyperthyroid rats compared with euthyroid rats. Concentrations of total SOD, Cu,Zn-SOD and GSH-PX were increased but that of Mn-SOD was decreased in hypothyroid animals. There were no differences among hyperthyroid, hypothyroid and euthyroid rats in the levels of coenzymes 9 or 10. The concentration of lipid peroxides, determined indirectly by the measurement of thiobarbituric acid reactants, was decreased in hyperthyroid rats but not in hypothyroid rats when compared with euthyroid animals. These findings suggest that free radicals and lipid peroxides are scavenged to compensate for the changes induced by hyper- or hypothyroidism.
1 We examined whether N-hydroxyethyl-1-deoxynojirimycin (miglitol), a new human anti-diabetic drug with e ects to inhibit a-1,6-glucosidase glycogen debranching enzyme and reduce the glycogenolytic rate as well as to inhibit a-1,4-glucosidase, could reduce infarct size in the rabbit heart. Rabbits were subjected to 30-min coronary occlusion followed by 48-h reperfusion. 2 The infarct size as a percentage of area at risk was not reduced by pre-ischaemic treatment with 1 mg kg 71 miglitol (42.7+4.0%, n=10) compared with the saline control group (41.7+2.3%, n=10). However, it was signi®cantly and dose-dependently reduced by pre-ischaemic treatment with 5 or 10 mg kg 71 of miglitol (25.7+4.5%, n=10, and 14.6+2.4%, n=10, respectively) without altering the blood pressure, heart rate or blood glucose level. However, there was no evidence of an infarct-size reducing e ect after pre-reperfusion treatment with 10 mg kg 71 of miglitol (35.0+3.0%, n=10). 3 Another 40 rabbits given 1, 5 and 10 mg kg 71 of miglitol or saline before ischaemia (n=10 in each) were sacri®ced at 30 min of ischaemia for biochemical analysis. Miglitol preserved signi®cantly the glycogen content, and attenuated signi®cantly the lactate accumulation in a dose dependent manner in the ischaemic region at 30 min of ischaemia. 4 Pre-ischaemic treatment, but not pre-reperfusion treatment, with miglitol markedly reduced the myocardial infarct size, independently of blood pressure and heart rate. A dose-dependent e ect of miglitol on infarct size, glycogenolysis and lactate formation suggests that the mechanism may be related to the inhibition of glycogenolysis. Thus, miglitol may be bene®cial for coronary heart disease as well as diabetes mellitus. Keywords: Myocardial infarction; ischaemia; a-glucosidase inhibitor; myocardium; glycogen Abbreviations: LV, left ventricle; Mig, miglitol; NADH, nicotinamide adenine dinucleotide; NADP, nicotinamide adenine dinucleotide phosphate; TTC, triphenyl tetrazolium chloride IntroductionBrief episodes of ischaemia and reperfusion before a subsequent prolonged period of ischaemia precondition the myocardium and reduce myocardial infarct size. This phenomenon is known as ischaemic preconditioning, and has been demonstrated in various animal species such as rats (Li et al., 1992), rabbits (Thornton et al., 1990), dogs (Murry et al., 1986 and pigs (Schott et al., 1990) and also in humans (Nakagawa et al., 1995). Since ischaemic preconditioning is not appropriate for clinical use, it is desirable to precondition the heart with chemicals (`pharmacological preconditioning') which exert a bene®cial e ect similar to ischaemic preconditioning without any side e ects. Several possible mediators by which ischaemic preconditioning protects the heart include adenosine (Liu et al., 1991), noradrenaline (Kariya et al., 1997), bradykinin (Goto et al., 1995), free radicals (Tanaka et al., 1994), the activation of protein kinase C (Ytrehus et al., 1994) and the opening of K ATP channels (Gross & Auchampach, 1992). Clinically, noradrenalin...
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