Chromosomal abnormalities in maternal and fetal tissues of magnesium- or zinc-deficient rats.

The effect of dietary deficiency during pregnancy of zinc or magnesium on maternal and fetal chromosomes was studied. Pregnant rats were given a zinc-deficient or a magnesium-deficient diet from the beginning of pregnancy and maternal bone marrow and fetal liver were removed on day 19 of gestation. Chromosome spreads were prepared and metaphases examined for abnormalities. Both magnesium- and zinc-deficient maternal bone-marrow and fetal liver cells showed significantly more chromosomal abnormalities than did those of controls. The chromosomal aberrations occurring in highest incidence in magnesium-deficient animals were terminal deletions and fragments. A higher than normal incidence of "stickiness" was also observed in cells from magnesium-deficient animals. In zinc-deficient animals, on the other hand, the chromosomal aberrations with the highest incidence were gaps and terminal deletions.     

Increased methionine synthetase activity in zinc-deficient rat liver

To study the effect of zinc deficiency on folate metabolism, three groups of male Sprague-Dawley rats (zinc deficient (ZD), restricted-fed (RF + Zn), and ad libitum-fed control (control] were given a semipurified 25% egg white protein diet. The ZD group received less than 10.3 nmol zinc/g of diet, while the RF + Zn and control groups were given 1620 nmol zinc/g of diet. After 6-7 weeks of feeding, severe zinc deficiency developed in ZD rats. Hepatic methionine synthetase activity was increased in the ZD group compared to both the RF + Zn and control groups, but hepatic 5,10-CH2-H4folate reductase activity was similar in all groups. This increased methionine synthetase activity found in zinc-deficient rats might induce secondary alterations in folate metabolism. These changes include significantly lowered plasma folate levels, decreased 5-CH3-H4folate in liver, and increased rates of histidine and formate oxidation. The latter two findings suggest that the available non-5-CH3-H4folate is increased in zinc deficiency.     

Phagocytosis by macrophages in zinc-deficient rats

Phagocytosis by polymorphonuclear cells has been found to be significantly reduced in zinc-deficient patients and this finding was confirmed in animal experiments. In order to find out whether phagocytosis by macrophages is similarly altered, experiments were conducted in three groups of 18 rats. Control, zinc-deficient and pair-fed rats were given ^99mTc nanocolloid intravenously. In ten other experiments (5 experimental and 5 control rats) ^99mTc-sulfur colloid was injected intravenously. The biodistribution was determined by a well-type gamma counter and the results were evaluated statistically. The greatest amount of radioactivity was taken up by the liver, followed by the spleen, lung and kidney. In both series of experiments however the zinc-deficient animals appeared to take up a greater amount of the radiotracer (P < 0.05).     

Effect of a zinc-deficient diet on nitrogen balance in rats

The effects of a zinc-deficient diet (1.5 mg/kg) on nitrogen balance in rats, fed ad libitum during 30 days, was tested. Three nitrogen balances, each of 5 days, were done on the 4th, 15th and 25th days. A pair-fed group, with a supplemented diet at 80 mg/kg of zinc, was used as control. No significant differences (P less than or equal to 0.05) in any nitrogen balances for True Digestibility, Operative Biological Value and body weight were found. Nevertheless a trend was observed in all studied variables, indicating that the proteins of the control diet were better utilized than those of the zinc-deficient ones. The variation of the Biological Value of the proteins in the zinc-deficient group along the experimental period was similar to the control group.     

Increased plasma pyridoxal-5′-phosphate when alkaline phosphatase activity is reduced in moderately zinc-deficient rats

It is generally believed that the zinc metalloenzyme alkaline phosphatase is required to hydrolyze phosphorylated forms of vitamin B-6 prior to their use. To test this hypothesis, rats were fed a liquid diet containing either adequate or moderately low zinc during gestation and lactation. Zinc deficiency was produced in dams evidenced by significant reductions in zinc concentration of plasma (49%), liver (25%), and femur (24%), and plasma alkaline phosphatase activity (48%). Plasma pyridoxal-5′-phosphate (PLP), which significantly increased (61%) in these same rats, was negatively correlated (r=−0.74,P<0.02) with plasma alkaline phosphatase activity. Maternal liver PLP concentration was unaffected by zinc status. The zinc and vitamin B-6 relationship seen in dams was less observable in offspring. Stimulation of erythrocyte alanine aminotransferase activity by exogenously added PLP in vitro tended to be higher in both moderately zinc-deficient mothers and their offspring, but the difference was not significant. Our results support the hypothesis that alkaline phosphatase activity is required for the hydrolysis of plasma PLP. Our results also suggest that zinc status as alkaline phosphatase activity should be defined in an individual if plasma PLP is to be used as an indicator of vitamin B-6 status.     

Maternal metabolism and teratogenesis in zinc-deficient rats

Embryos removed at 11.5 days gestation from pregnant rats allowed a zinc-deficient diet from the time of mating showed a high frequency of malformations of all organ systems. There were, however, large differences between litters of individual dams. Comparison of the daily food intake of zinc-deficient dams with the appearance of the embryos suggested that fluctuations in the maternal serum zinc levels induced by feeding or fasting influenced the availability of zinc to the embryos. By cyclically feeding zinc-deficient dams to a predetermined schedule, low maternal serum zinc levels were induced at selected stages of development. This was accompanied by specific malformations of the organs developing at that time.     

Effect of polaprezinc on taste disorders in zinc-deficient rats

The effect of polaprezinc, a chelate compound consisting of zinc ion and L-carnosine, on abnormalities of taste sensation induced by feeding a zinc-deficient diet to rats was examined by using the two-bottle preference test (quinine hydrochloride as a bitter taste and sodium chloride as a salty taste). Rats were fed either a zinc-deficient or a zinc-sufficient diet. The zinc-deficient diet increased the preference for both taste solutions, while polaprezinc (at doses of 3 and 10 mg/kg) restored the altered taste preferences. We also evaluated the proliferation of taste bud cells using 5-bromo-2'-deoxyuridine (BrdU). The BrdU incorporation into taste bud cells was significantly reduced in rats fed a zinc-deficient diet compared with rats fed a zinc-sufficient diet (from 50.8% to 45.0%, p<0.05) and this reduction was reversed by polaprezinc at doses of 1, 3, and 10 mg/kg, increasing to 50.2%, 53.5%, and 52.5%, respectively. These findings indicate that zinc deficiency induces the delayed of proliferation of taste bud cells, while polaprezinc improves cell proliferation. In conclusion, polaprezinc had a therapeutic effect in a rat model of abnormal taste sensation. Its mechanism of action was suggested to involve improvement of the decrease in taste bud cell proliferation caused by zinc deficiency.     

Melatonin enhances guanylate cyclase activity in a variety of tissues

Summary The objective of the present investigation was to determine if melatonin at physiological concentrations might have part of its mechanism of action through enhancement of guanylate cyclase (E.C.4.6.1.2) activity. Melatonin enhanced guanylate cyclase activity two-three fold in rat anterior pituitary, thyroid, testis, ovary, liver and small intestine at the 1 nanomolar concentration. Some stimulation of hepatic guanylate cyclase activity by melatonin was seen at concentrations as low as 1 picomolar. There was no stimulation of guanylate cyclase activity at concentrations below 1 picomolar. Maximal enhancement of guanylate cyclase activity was seen at the 1 nanomolar concentration of melatonin with no further enhancement being observed with increasing the concentration to the micromolar range. Thus, the data in the present investigation indicates that at concentrations at which melatonin is known to cause physiological effects, melatonin does cause an enhancement of the activity of the guanylate cyclase-cyclic GMP system.     

Zinc homeostasis in the hippocampus of zinc-deficient young adult rats

On the basis of the evidence of the transient learning impairment of young adult rats fed a zinc-deficient diet for 4 weeks, zinc concentration in the hippocampus was examined in the zinc-deficient rats to understand the mechanism of brain dysfunction in zinc deficiency. Zinc concentration in the hippocampus, as well as that in other brain regions, was not decreased by 4-week zinc deprivation. When Timm's stain, with which histochemically reactive zinc in the presynaptic vesicles is detected, was compared between the control and zinc-deficient rats, the intensity of Timm's stain in the hippocampus was almost the same between them. In the hippocampus, zinc concentration in the synaptosomal fraction was not also decreased by 4-week zinc deprivation, whereas that in the crude nuclear fraction was significantly increased. These results suggest that zinc concentration in the presynaptic vesicles is not decreased in young adults rats by 4-week zinc deprivation. It is likely that zinc-requiring systems in the nucleus are more responsive to zinc deficiency than vesicular zinc. This responsiveness appears to be involved in the transient learning impairment.     

Zinc-binding proteins (ligands) in brains of severely zinc-deficient rats

Previous studies from this laboratory reported the presence of a metallothionein-like protein in brain with an apparent estimated molecular weight of 13,000–15,000 daltons. The synthesis of this protein, which incorporates large quantity of cysteine, is stimulated following administration of zinc and copper and is blocked by actinomycin D. In this study, we report that the synthesis of this metallothionein-like protein is considerably lower in brains of severely zinc-deficient rats in comparison with pair-fed orad libitum fed groups. Furthermore, incubation of partially purified metallothionein-like protein with⁶⁵Zn and chromatography on DEAE A-25 Sephadex produced similar elution patterns in the three experimental groups. However, the extent of binding of⁶⁵Zn to the metallothionein-like protein from the zinc-deficient rats was significantly (p<0.05) lower than the control groups. On the other hand, the total concentration of zinc in brains of zinc deficient rats did not vary from control groups. Since the synthesis of this metallothionein-like protein is reduced by zinc deficiency and is stimulated following administration of zinc, we postulate that the free pool of zinc may regulate the synthesis of its binding protein in the brain.     

Impaired microtubule assembly in brain from zinc-deficient pigs and rats

• 1.1. Microtubule reassembly was studied in brain extracts from pigs and rats deficient in zinc and from zinc-supplemented controls. Tubulin in extracts from zinc-deficient animals showed an impaired ability to repolymerize compared with extracts from control animals.
• 2.2. Crude microtubule protein isolated from zinc-deficient rat brain contained less free SH groups than that isolated from zinc-supplemented animals.
• 3.3. It is concluded that variation in zinc concentration close to the physiological range can influence microtubule assembly, and that zinc may have some function in microtubule polymerization in vivo.

     

Transforming growth factor-α immunoreactivity in a variety of epithelial tissues

Abstract. The immunohistochemical expression of transforming growth factor-alpha (TGFα) has been examined in a range of normal adult epithelial tissues from both man and rat using an anti-hTGFα monoclonal antibody (GF10). No differences in distribution were apparent between man and rat. In the continually renewing epithelium of the gastrointestinal tract, no staining was seen within the proliferative compartments, but strong immunoexpression was noted in various differentiated populations. In the testis, the spermatogonia were unstained, but the more luminally orientated germ cells were strongly positive. In the gastrointestinal tract, at least, any mitogenic action of TGFα must be mediated through a relatively long paracrine loop. In contrast, the differentiated parenchyma of kidney, salivary gland and liver remained unstained apart from collecting ducts in the kidney, striated ducts in salivary glands and bile ducts in the liver. The association of TGFα with tubule formation was reinforced by the very strong staining of newly forming bile ducts in a model of liver oval cell proliferation. Thus, in all the epithelia studied there was a distinct spatial pattern of TGFα immunoreactivity.     

Syk expression and novel function in a wide variety of tissues.

Syk protein-tyrosine kinase has been implicated in a variety of hematopoietic cell responses, in particular immunoreceptor signaling events that mediate diverse cellular responses including proliferation, differentiation, and phagocytosis. On the other hand, Syk exhibits a more widespread expression pattern in nonhematopoietic cells like fibroblasts, epithelial cells, breast tissue, hepatocytes, neuronal cells, and vascular endothelial cells and has been shown to be functionally important on these cell types. Thus, Syk appears to play a general physiological function in a wide variety of cells. In this article, we briefly review the current literature regarding the expression and novel function of Syk in various cells and tissues.     

Quercetin protects radiation-induced DNA damage and apoptosis in kidney and bladder tissues of rats

Abstract

Ionizing radiation (IR) can induce cell damage and cell death through the reactive oxygen species generated by radiolytic hydrolysis. The present study was aimed to determine the possible protective effects of quercetin, a well-known antioxidant agent, against IR-induced bladder and kidney damage in rats. Sprague-Dawley rats were exposed to 8-Gy whole-abdominal IR and given either vehicle or quercetin (20 mg/kg, ip). Rats were decapitated at either 36 h or 10 days following IR, where quercetin or vehicle injections were repeated once daily, and kidney and bladder samples were obtained for the determination of myeloperoxidase and caspase-3 activities, an index of tissue neutrophil infiltration and apoptosis, respectively. Radiation-induced inflammation was evaluated through tissue cytokine, TNF-α levels. In order to examine oxidative DNA damage, tissue 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. All tissues were also examined microscopically. In the saline-treated irradiation groups, myeloperoxidase and caspase-3 activities, 8-OHdG and TNF-α levels were found to be increased in both tissues (p < 0.05). In the quercetin-treated-IR groups, all these oxidant responses were prevented significantly (p < 0.05). The present data demonstrate that quercetin, through its free radical scavenging and antioxidant properties, attenuates irradiation-induced oxidative organ injury, suggesting that quercetin may have a potential benefit in radiotherapy by minimizing the adverse effects and will improve patient care.     

Atrial natriuretic factor prohormone peptides are present in a variety of tissues.

Utilizing two sensitive and specific radioimmunoassays which immunologically recognize 1) the 98 amino acid (a.a.) N-terminus and 2) the 28 a.a. C-terminus (i.e., a.a. 99-126) of the 126 a.a. atrial natriuretic (ANF) prohormone, various tissues including aorta, kidney, small intestine, colon, liver, spleen, lung, and testis were investigated to determine if the ANF prohormone was present in any of these tissues in addition to its previously demonstrated presence in heart and brain. Aorta with 62.3 +/- 3 ng of the N-terminus/g of tissue and 51.6 +/- 1.8 ng of the C-terminus of the ANF prohormone/g of tissue had the highest concentration of the ANF prohormone of the previously undescribed ANF prohormone-containing tissues. The next highest concentration of the ANF prohormone was in the intestine, followed by lung and spleen. Pancreas, liver and kidney had similar levels of immunologically recognized ANF prohormone (approximately 1/50 of the aorta), while the testis and cerebrum had low levels. These results suggest that a much larger variety of tissues synthesize and/or store the ANF prohormone than is presently thought.