Calcium iodate-another effective blocker of radioiodine uptake by the thyroid gland.

KI and KIO3 are the commonly used prophylactic drugs for the protection of thyroid glands against radioiodine. In this study, we have demonstrated the use of another iodine containing salt, calcium iodate [Ca(IO3)2], as an effective blocker of radioiodine uptake by the thyroid gland in rats. Ca(IO3)2 is permitted by the FDA as a food additive and is "generally regarded as safe" (GRAS, CFR No.1206). We have also compared the efficacy of Ca(IO3)2 with KIO3 in blocking thyroidal uptake of radioiodine, which could be important considering the better shelf life of Ca(IO3)2. Laboratory rats were administered 131I and stable iodide in the form of KIO3 or Ca(IO3)2 was given orally, 2 h after the administration of 131I. All the animals were monitored for whole body retention (WBR) of 131I, at 24 h and further for 14 d. The results of the present study provide us with evidence that Ca(IO3)2 can serve as another promising radioiodine blocker, and is as equipotent as KI/KIO3 in protecting the thyroid gland. We have not found any studies that examined the property of Ca(IO3)2 in blocking radioiodine uptake by the thyroid gland and the present study is an attempt in this direction.

Difficulty in dislodging in vivo fixed radiostrontium.

Many trials based on the basic phenomena of isotopic dilution, adsorption, ion exchange, chelation, etc., have been attempted for the decorporation of radiostrontium, particularly Sr, after its entry in the in vivo system. We have recently demonstrated a non-isotopic carrier effect of some common calcium salts (calcium = 9 mg mL) to reduce the whole body retention of radiostrontium, if administered within 2 h after radiostrontium exposure and furthermore once daily, in rats, supplemented with calcium fortified diet. However, 25-30% of radiostrontium (compared to 50-60% in untreated animals) was still found to be retained in the animal even after 2 wk of treatment. Trial of some simple interventional measures, which would not adversely affect the animal metabolism, like pyrophosphate and magnesium sulfate, sodium citrate, chitin (a bio-absorbent), crown ether (a metal-chelator), and ammonium chloride, was therefore attempted to dislodge this remaining radiostrontium by switching over these animals to normal diet and subjecting them to different lines of treatment with these simple interventions through diet and drinking water separately for a further 4 wk. However, this remaining portion of radiostrontium is fixed in the bone and is difficult to dislodge.

An effective and better strategy for reducing body burden of radiostrontium.

In this study we have examined the effect of different calcium salts, Ca gluconate (CaG), Ca lactate (CaL), Ca carbonate (CaC) and Ca phosphate (CaP), on the clearance of radiostrontium (*Sr) administered either intraperitoneally (ip) (*Sr-ip group) or orally (*Sr-oral group) in rats. The influence of these Ca salts was examined in a group of animals administered *Sr ip, while the effect of three Ca salts (CaG, CaL and CaP) was studied in another group of rats given *Sr orally and compared with that of Ca alginate (CaA), normally advised for *Sr decorporation. Rats from both groups were subdivided into control and four experimental subgroups and were housed individually. The experimental subgroups were given the respective Ca salts (elemental Ca = 9 mg/rat/day) 2 h post 85Sr, and thereafter once daily. In the *Sr-ip group, CaG was administered ip while the other Ca salts were given orally. In the *Sr-oral group all Ca salts were administered orally. In addition, the diet of all the experimental subgroups was supplemented with the respective Ca salts to 2% elemental Ca. The whole-body retention (WBR) of *Sr in animals treated with Ca salts was found to be significantly reduced from 50-60% at 24 h to 20-30% at the end of 15 days compared with 70-80% at 24 h to 50-60% at the end of 15 days in the untreated control animals. The results strongly suggest that CaA could be replaced by any of the commonly used Ca salts for curtailing the WBR of *Sr. CaG which was administered ip, in the *Sr-ip group, was found to be more effective in reducing the WBR of *Sr.

Potassium iodate and its comparison to potassium iodide as a blocker of 131I uptake by the thyroid in rats.

Potassium iodide is the preferred thyroid blocker for personnel handling radioiodine and is recommended as a prophylaxis for the population in the near-field of a nuclear reactor which would be likely to be exposed to radioiodine in an accidental breach of containment. However, in hot and humid climates, this hygroscopic chemical has a poor shelf life due to hydrolytic loss of iodine vapors. On the other hand, another iodine-rich salt, potassium iodate (KIO3), is quite stable and has a much longer shelf life. The present study compares potassium iodide and KIO3 as thyroid blockers and examines the appropriate time at which they should be administered in case of radioiodine exposure. Either of the two were given in recommended dosage (100 mg stable iodine per 70 kg body weight) at -2, 0, +2, +4, +6, and +8 h after administration of tracer quantities of radioiodine (131I) to age-, weight-, and sex-matched rats. 131I uptake in thyroid was measured 24 h after its administration in the experimental animals and compared with placebo administered controls. Results suggest that KIO3 is as effective a thyroid blocking agent as potassium iodide. In comparison to controls, 24-h thyroid uptake of 131I can be substantially reduced if potassium iodide or KIO3 is given to the animals within 2-4 h after exposure to 131I. Another noteworthy observation is that KIO3 is effective even at 8 h when administered at twice the usual dosage in comparison to the single dose, which does not show appreciable thyroid blocking properties after 8 h.

The role of calcium in the modulation of the hepatic anti-oxidant defence system.

A normocalcemic animal model of vitamin D (vit. D)-deficiency has been successfully developed by feeding a high calcium (Ca2+) diet to vit. D.-deficient rats. The modulating role of Ca2+ on the hepatic antioxidant defence system and lipid peroxidation has been evaluated in this model. Partial restoration of liver function was noted in these rats following extra Ca2+ feeding. Serum alkaline phosphatase and alanine aminotransferase reverted to a normal level. The reduced levels of hepatic SOD and glutathione peroxidase in vit. D.-deficient rats, were also increased after extra Ca2+ supplementation. Even elevated lipid peroxidation due to vit. D.-deficiency was reduced after feeding the extra Ca(2+)-supplemented diet. However, catalase activity remained at the control level throughout the study. The results provide important evidence that normocalcemia is essential for maintaining the hepatic antioxidant defence and controlling lipid peroxidation in the in vivo milieu.

Altered hepatic function in vitamin D-deprived rats.

Rats were rendered vitamin D-deficient by housing them in a room free of ultraviolet light and maintaining them for 20 weeks on a diet devoid of only vitamin D. The vitamin D-deficiency state was confirmed by the undetectable levels of circulating vitamin D metabolites, severe hypocalcaemia and significantly reduced intestinal calcium transport. Liver function and protein metabolism in these rats were assessed by bromosulphthalein (BSP) clearance, liver histology, plasma transaminases and alkaline phosphatase, and 14C-labelled amino acid incorporation into liver and plasma proteins. Subtle alterations in hepatic function, as manifested by delayed BSP clearance, elevated levels of plasma transaminases and alkaline phosphatase, were noticed. Liver histology revealed changes consistent with periportal necrosis. Synthesis of liver and plasma proteins were reduced by 26-34% (P less than 0.01), without affecting the circulating levels of plasma proteins, suggesting reduced protein turnover in vitamin D-deprived rats. The results strongly suggest the direct/indirect involvement of vitamin D in mediating the altered liver function.

Radiopharmacological profiles of tracers under pathophysiological conditions. Bone uptake of 99mTc-phytate in vitamin D deficient rats.

The radiopharmaceutical 99mTc-phytate, formed by reacting the phosphatic ligand, myo-inositol hexakisphosphate with a reduced form of 99mTcO4-, is widely employed in diagnostic nuclear medicine for scinti-imaging the RE system. Despite it being a compound derived from a ligand containing phosphatic functional moieties it does not concentrate to a significant extent in the osseous tissue following i.v. injection into animals or humans. Neither has there been any clinical report citing its localization in the skeletal tissue consequent to its i.v. injection into patients with different types of pathophysiological conditions/metabolic bone disorders. In the course of our study of the homing characteristics of radiopharmaceuticals into specific organ systems or secondary target sites we found that 99mTc-phytate could be directed to some extent into the skeletal tissues of experimental rats by altering its physiological milieu--viz. by decreasing blood calcium levels and increasing bone resorption. Such an altered physiologic condition is obtained by experimentally inducing vitamin D deficiency in animals. Our results show that 8-10% of the administered dose could be redirected to the bone matrix but at the expense of the liver. The study also indicates that many so-called organ specific 99mTc-radiopharmaceuticals could have more than one target tissue/organ system for accumulation consequent to being introduced into the systemic circulation. In a number of instances the secondary target may be masked and may be elicited only under certain specific pathophysiologic conditions.

Radiopharmacological profiles of tracers under pathophysiological conditions. 99mTc-methylene diphosphonate uptake by bone in altered thyroid status.

The uptake of 99mTc-MDP, a skeletal radiotracer, was studied at early and late (3 h) time intervals in rats induced with altered thyroid status. Thyroid dysfunction resulted in disturbances in bone mineral metabolism. Rats rendered hypothyroid showed an overall retardation in growth and also considerably reduced skeletal uptake, especially at early time periods. On the other hand, rats rendered hyperthyroid did not show any significant alteration of the skeletal uptake as compared with controls despite enhanced bone turnover normally observed in hyperthyroidism.

Effect of altered thyroid status on the transport of hepatobiliary radiopharmaceuticals.

The effect of induced hypothyroidism (by feeding an antithyroid drug-propylthiouracil) on the transport and clearance of the routinely used hepatobiliary radiopharmaceuticals--radioiodinated iodine-131 (131I) rose bengal and technetium-99m-N-(4-n-butylphenylcarbamoylmethyl) iminodiacetate, was studied in the rats. Hypothyroidism was associated with depressed growth and retarded clearance of these radiotracers from the in vivo system. Treatment of the hypothyroid rats with thyroxine (2-5 micrograms/100 g b.w. day) for 6 wk, restored these parameters towards normal values. These data suggest that delayed clearance of these hepatobiliary tracers could be related to reduced metabolic rate accompanied with the hypotonia and hypomotility of intestine normally observed in the hypothyroid state.

Effects of propylthiouracil, methimazole and thyroidectomy on liver and plasma proteins: differential response to thyroxine.

Differential effects of propylthiouracil (PTU), methimazole (MMI) and thyroidectomy (Tx) on liver and plasma proteins have been studied in rats, some of which have been simultaneously treated with L-thyroxine (T4). Although the absolute liver weights were lower in all hypothyroid groups, the relative liver weights (g/100 g) were significantly higher in PTU and MMI groups, while in Tx group they were lower. T4 administration raised the absolute liver weights in all groups, even though there was no significant difference between relative weights in PTU and MMI groups. In Tx group, however, the relative weight was restored to control level. One of the constituents responsible for the increased relative liver weight was liver protein. The increased liver protein concentration (mg/g) was, however, not reflected in the synthesis rate which was uniformly low in all groups inspite of T4 therapy. Plasma albumin concentration was raised in hypothyroid rats which did not respond to T4 therapy. On the other hand, increased total plasma protein level was restored to normal. Relative 14C-glycine incorporation into albumin, fibrinogen, seromucoids and total proteins was reduced from 14 to 30%, 5.2 to 19% and 13 to 23% of control in PTU, MMI and Tx groups, respectively. Of these, only MMI and Tx groups appeared to be responsive to T4 therapy. Of all the protein fractions, fibrinogen synthesis was least affected by various treatments. To some extent these observations may be explained on the basis of altered general endocrine status and specific extra-thyroidal effects, rather than on the basis of thyroid status alone.

Stimulation of intestinal calcium transport and bone calcium mobilization by prolactin in vitamin D-deficient rats.

In vitamin D-deficient rats intestinal calcium transport increased significantly 4 hours after an injection of prolactin, reached a maximum after 8 hours, and declined to preinjection levels after 24 hours. Similarly, in vitamin D-deficient rats fed a diet low in calcium or phosphorus prolactin stimulated an increase in serum calcium in both groups and an increase in serum phosphorus in the rats fed the diet low in phosphorus. Thus it appears that prolactin affects organs involved in calcium regulation in a manner that is independent of the vitamin D endocrine system.

Role of the hypophysis in the regulation of vitamin D metabolism.

Hypophysectomy of animals given maintenance levels of vitamin D and adequate levels of dietary calcium and phosphorus brings about a marked reduction in plasma 1,25-dihydroxyvitamin D3 levels and a significant elevation in plasma 24,25-dihydroxyvitamin D3 levels. The hypophysectomy, as expected, results in reduced growth and lowered plasma levels of inorganic phosphorus. The injection of growth hormone markedly increases plasma levels of 1,25-dihydroxyvitamin D3 in hypophysectomized animals while bringing about a reduction in 24,25-dihydroxyvitamin D3 levels. These results support the idea that the hypophysis plays a role in the regulation of vitamin D metabolism and that growth hormone either directly or indirectly is one of the hypophyseal factors bringing about this regulation.

Liver vitamin A stores in chronic alcoholism in rats: effect of propylthiouracil treatment.

Administration of alcohol to rats through drinking water for 8 weeks produced a significant decrease in the liver vitamin A stores without causing any change in the plasma vitamin A levels. Treatment of the alcoholic rats with propylthiouracil for 2 weeks restored the liver vitamin A reserves to control levels.