Evaluation of the cell death pathway and apoptosis-stunning effect relationship after low- and high-dose I-131 administrations in rat thyroid tissue.

OBJECTIVES: This study had two aims; (1) to describe the cell death pathway (apoptosis or necrosis) induced by a low and high dose of radioiodine (I-131) in rat thyroid tissue in in vivo conditions and (2) to determine the role of apoptosis in the development of "stunning effect" in the thyroid tissue with low and high doses of I-131 application. DESIGN: The experimental group consisted of 18 rats; low and high I- 131 doses with a 1-week interval were administered to this group. At first, low doses were injected intraperitoneally (i.p.) (net injected dose was 51.54 +/- 8.6 microCi). After 1 week of the low-dose injection, high doses were also injected (net injected dose was 934.9 +/- 211.8 microCi). Thyroidal I-131 uptakes for both low- and high-dose applications were calculated by using a gamma camera after 24 hours of injections. Immediately after the uptake calculation, thyroid tissues were resected. A control group of 10 rats was also included in the study; in this group, I-131 was not administered. Thyroid tissues of this group rats were also resected. DNA was extracted from thyroid tissues, and damage was examined with the "DNA ladder by agaroz gel electrophoresis." RESULTS: Thyroidal I-131 uptakes were calculated as 11.3% +/- 3.6% and 9.8% +/- 5.3% at the 24th hour after low- and high-dose I-131 applications, respectively. When the low- and high-dose uptake values were compared for each rat; a significant relationship was not found between thyroidal uptakes and injected low and high doses of I-131. When the chromosome images were examined, there was healthy DNA appearance in 1 rat; in 4 rats, only necrotic hyperfragmentations were observed; in 9 rats, both apoptotic specific fragmentations and necrotic hyperfragmentations were observed; and in 4 rats, apoptosis, necrosis, and healthy DNA appearances were seen together. In none of the rats, specific fragmentations concordant only with apoptosis was found. When the thyroidal uptake alterations were taken into consideration, significant difference was not found between first and second uptake calculations (p = 0.28). No significant relationship was also observed between thyroidal uptake alterations and apoptosis-necrosis-healthy DNA findings. Additionally, when we take into consideration the DNA results of only 13 of the rats that had reduced thyroidal uptake, a significant relationship could also not be observed between reduced uptake and apoptotic, necrotic, or healthy tissue findings. Interestingly, apoptotic and necrotic tissue or only necrotic, tissue findings were observed in the other 5 rats which had increased thyroidal uptake. CONCLUSIONS: Following I-131 administration, two types of cell death--both apoptosis and necrosis findings--have been observed in most of the rats. We think that the decreased uptake values are because of the probable stunning effect in thyroid tissue. We also investigated whether the stunning effect is related to apoptosis. According to our results, it can be concluded that the stunning effect is not related to tissue damage, cell decrease, or cell death. Alternatively, we think that this can be related to a radiation-induced reduction of iodine uptake/metabolism or a modified iodine transport mechanism. For further in vivo studies, this experimental model using normal rat thyroid tissue may be useful in investigating the cell death pathways induced by I-131 and its probable roles in the development of the stunning phenomenon.

Effects of fasudil, a Rho-kinase inhibitor, on myocardial preconditioning in anesthetized rats.

The aim of this study was to examine the effects of fasudil, a Rho-kinase inhibitor, on ischemic preconditioning and carbachol preconditioning in anesthetized rats. The total number of ventricular ectopic beats was markedly augmented with fasudil at 0.3 mg/kg and depressed with fasudil at 10 mg/kg. Fasudil at 10 mg/kg also markedly decreased the ventricular tachycardia incidence. Ischemic preconditioning, induced by 5 min coronary artery occlusion and 5 min reperfusion, decreased the incidence of ventricular tachycardia and abolished the occurrence of ventricular fibrillation. The incidences of ventricular tachycardia and ventricular fibrillation in the fasudil (10 mg/kg) + ischemic preconditioning group were found to be similar to the ischemic preconditioning group. However, low doses of fasudil (0.3 and 1 mg/kg) appeared to prevent the antiarrhythmic effects of ischemic preconditioning. Carbachol (4 microg/kg/min for 5 min) induced marked reductions in mean arterial blood pressure, heart rate and abolished ventricular tachycardia. Marked reductions in ventricular ectopic beats and ventricular tachycardia were noted in the fasudil (10 mg/kg) + carbachol preconditioning group. Lactate levels were markedly reduced in the ischemic preconditioning group and this reduction was prominently inhibited with fasudil at 1 mg/kg. Ischemic preconditioning caused a marked decrease in plasma malondialdehyde levels. Fasudil (10 mg/kg), ischemic preconditioning and carbachol preconditioning each generated marked reductions in ischemic myocardial malondialdehyde levels. Decreases in infarct size were observed with fasudil (10 mg/kg) treatment, ischemic preconditioning and carbachol preconditioning when compared to control. These results suggest that low doses of fasudil (0.3 and 1 mg/kg) appeared to prevents the effects of ischemic preconditioning and carbachol preconditioning, but a high dose of fasudil (10 mg/kg) was able to produce cardioprotective effects on myocardium against arrhythmias, infarct size or biochemical parameters and mimic the effects of ischemic preconditioning in anesthetized rats.

Relationships between tensile strength, ascorbic acid, hydroxyproline, and zinc levels of rabbit full-thickness incision wound healing.

PURPOSE: This work was carried out to follow up the healing of full-thickness incision wounds opened on the back skin of rabbits in order to gain insight into the periodical correlation among such factors as ascorbic acid, collagen (hydroxyproline), the zinc content, and tensile strength of wound tissue. The need to provide vitamin C or zinc supplements after such wound incisions is also discussed. METHODS: Full-thickness incision wounds and the ascorbic acid and hydroxyproline levels were measured in 24 rabbits by spectrophotometric methods on day 0 and on the 3rd, 5th, 7th, and 15th days after operation. The tensile strength was measured by a polygraph using a force displacement transducer. The zinc levels of the wounds were measured by atomic absorption spectrophotometry. RESULTS: The zinc and hydroxyproline levels reached the peak levels on the 5th day, but the tensile strength of wound increased sharply on the 7th day after wounding while the zinc levels did not change. These results indicated that in the first 7 days of wound healing, high levels of ascorbic acid, hydroxyproline, and zinc cumulation occurred in the wound tissue, and the tensile strength reached its highest level on the 15th day without any supplementation. CONCLUSION: The supplementation of zinc and/or ascorbic acid should therefore be given just at the beginning of the wounding period, especially if there is deficiency of these nutrients.