Zinc Deficiency Enhances the Induction of Micronuclei and 8-Hydroxy-2′-Deoxyguanosine Via Superoxide Radical in Bone Marrow of Zinc-Deficient Rats

The aim of the present study was to examine whether zinc (Zn) deficiency augmented the frequency of micronuclei, an indicator of chromosome aberration, and the induction of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of cellular DNA damage derived from oxidative stress, in rat bone marrow cells or not. Both the frequency of micronuclei and the induction of 8-OHdG were significantly increased in rats fed with a Zn-deficient versus a standard diet for 6 weeks (p?<?0.005). The supplementation of Zn with a standard diet for 4 weeks to rats fed with a Zn-deficient diet for 6 weeks restored the enhanced induction of micronuclei and 8-OHdG to levels comparable to those seen in rats fed with a standard diet for 10 weeks, indicating that the shortage of Zn in the body is involved in the induction of micronuclei and 8-OHdG. Again, the membrane-permeable superoxide dismutase mimetic superoxide scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, treatment (100 μmol/kg, twice a day) for 10 days prior to the termination of dietary treatment reduced the induction of micronuclei and 8-OHdG in rats fed with a Zn-deficient diet for 6 weeks to levels comparable to those in rats fed with a standard diet for 6 weeks, indicating that superoxide radical participates in the induction of micronuclei and 8-OHdG. In fact, the endogenous superoxide scavenger, Cu/Zn superoxide dismutase, was significantly reduced in the bone marrow cells of rats fed with a Zn-deficient diet for 6 weeks when compared to those of rats fed with a standard diet for 6 weeks (p?<?0.005). These observations demonstrate that Zn deficiency elevates the frequency of micronuclei and the induction of 8-OHdG through an increase in the biological action of the superoxide radical. This suggests an increase in carcinogenic initiation resulting from Zn deficiency-induced oxidative stress.     

Zinc-deficient rat embryos have increased caspase 3-like activity and apoptosis

Caspase activity is a hallmark of apoptosis. Given that maternal zinc (Zn) deficiency results in apoptosis in the rat embryo, we assessed caspase activity in Zn-deficient embryos. Mid-gestation rat embryos were collected from dams fed either a Zn-deficient (0.5 Zn/g) diet ad libitum, or a Zn-adequate (25 microg Zn/g) diet ad libitum or pair fed to dams fed the Zn-deficient diet. Embryos from dams fed the Zn-adequate diet had a normal level of cell death, while embryos from the dams fed the Zn-deficient diet had either increased or normal levels of cell death. Zn-deficient embryos displaying increased cell death had increased caspase activity. Embryos with normal levels of cell death, regardless of maternal diet, had similar caspase activities. Thus, Zn-deficiency-induced apoptosis in vivo is associated with increased caspase activity.     

Mast cells are required for the development of renal fibrosis in the rodent unilateral ureteral obstruction model

Mast cells are associated with inflammation and fibrosis. Whether they protect against or contribute to renal fibrosis is unclear. Based on our previous findings that mast cells can express and secrete active renin, and that angiotensin (ANG II) is profibrotic, we hypothesized that mast cells play a critical role in tubulointerstitial fibrosis. We tested this hypothesis in the 14-day unilateral ureteral obstruction (UUO) model in rats and mast cell-deficient (MCD) mice (WBB6F1-W/Wv) and their congenic controls (CC). In the 14-day UUO rat kidney, mast cell number is increased and they express active renin. Stabilizing mast cells in vivo with administration of cromolyn sodium attenuated the development of tubulointerstitial fibrosis, which was confirmed by measuring newly synthesized pepsin-soluble collagen and blind scoring of fixed trichrome-stained kidney sections accompanied by spectral analysis. Fibrosis was absent in UUO kidneys from MCD mice unlike that observed in the CC mice. Losartan treatment reduced the fibrosis in the CC UUO kidneys. The effects of mast cell degranulation and renin release were tested in the isolated, perfused kidney preparation. Mast cell degranulation led to renin-dependent protracted flow recovery. This demonstrates that mast cell renin is active in situ and the ensuing ANG II can modulate intrarenal vascular resistance in the UUO kidney. Collectively, the data demonstrate that mast cells are critical to the development of renal fibrosis in the 14-day UUO kidney. Since renin is present in human kidney mast cells, our work identifies potential targets in the treatment of renal fibrosis.     

Dietary zinc deficiency decreases plasma concentrations of vitamin E

Experiments were conducted to examine the effects of dietary zinc (Zn) upon plasma vitamin E (E) concentrations to test the hypothesis that there may be a significant dietary interaction between these two nutrients. Weanling female Sprague-Dawley rats were fed diets that were (i) Zn-deficient (less than 0.9 micrograms Zn/g diet) ad libitum; (ii) Zn-adequate (50.9 micrograms Zn/g diet), pair-fed to the Zn-deficient group; and (iii) Zn-adequate (50.9 micrograms Zn/g diet) ad libitum. Plasma E in Zn-deficient animals (4.02 +/- 1.20 micrograms/ml) was significantly reduced (P less than or equal to 0.05) compared with results in both Zn-adequate pair-fed (9.21 +/- 0.70 micrograms/ml) and Zn-adequate ad libitum-fed (9.47 +/- 0.90 micrograms/ml) animals. Zn deficiency in this model system also resulted in significant (P less than or equal to 0.05) reductions in femur and plasma Zn concentrations as well as in plasma retinol, plasma triglyceride, and plasma cholesterol concentrations. Plasma albumin and total plasma protein concentrations were normal in Zn-deficient animals. With dietary Zn deficiency, the decrease in plasma E appeared to be out of proportion to associated decreases in plasma triglyceride and plasma cholesterol concentrations. Since E is associated with plasma lipoproteins, these data suggest that lipid and/or E malabsorption may be a consequence of Zn deficiency. In response to increased dietary intake of E, increments of plasma E were lower in Zn-depleted than in Zn-adequate, pair-fed animals. These findings suggest that dietary Zn deficiency possibly may increase the nutritional requirement for E necessary to maintain adequate plasma concentrations.     

Maternal and fetal iron accumulation in Zn-deficient and salicylate-treated rats

Nonhemoglobin Fe (non Hb−Fe) content in fetal serum and liver is much higher than in maternal serum and liver. After feeding a Zn-deficient diet to pregnant rats from d 0 to 21, non Hb−Fe content in maternal and fetal serum and liver was increased. After oral application of salicylic acid (300 mg/kg) from d 16 to 20 to normally fed and Zn-deficient dams, non Hb−Fe content in maternal and particularly in fetal serum and liver was drastically increased. In the kidney, Fe was accumulated to a small amount resulting from Zn deficiency and salicylate treatment. Fe accumulation in the liver occurred in all cell fractions, particularly in microsomes. Fe accumulation was confirmed and extended histochemically by Prussian blue staining. It is assumed that salicylate increases intestinal Fe resorption and fetal transfer of Fe. It is discussed that salicylate nephrotoxicity and its enhancement by Zn deficiency is not caused by an Fe-dependent mechanism. This work is supported by the German Research Foundation (Sfb 174)     

Dietary Zn deficiency does not influence systemic blood pressure and vascular nitric oxide signaling in normotensive rats

Because zinc (Zn) is an important component for cell protection against certain oxygen species, it has been suggested that Zn deficiency impairs the potent oxidant defense capacity, which is constitutively provided in the vascular system. However, the influence of dietary Zn deficiency on systemic blood pressure and vascular system is controversial and unclear. We therefore examine the effect of dietary Zn deficiency on systemic blood pressure, a potent superoxide scavenger, aortic Cu/Zn superoxide dismutase (SOD) activity, a most representative synthase of the endothelium-derived relaxing factor, and aortic endothelial nitric oxide synthase (eNOS) expression. Furthermore, the direct effects of intravenous administration of NOS inhibitor, N ^ω-nitro-l-arginine methyl ester (l-NAME), and a SOD mimetic compound, tempol, in normotensives were tested in Wistar-Kyoto (WKY) rats. A Zn-deficient diet (4 wk) contributed to growth retardation, the decrease in thymus weight, and the lower levels of serum Zn compared with the standard diet group. However, no significant difference in conscious systolic and diastolic blood pressure was found in the Zn-deficiency group. The administration of l-NAME caused an increase in the mean arterial pressure (MAP) levels in the two groups of rats and the involvement of the vasodilator nitric oxide (NO) in the regulation of systemic BP in the normotensive state. On the other hand, administration of the superoxide scavenger, tempol, led to a decrease in MAP levels in the two groups of rats, indicating the participation of the oxygen free radical, superoxide, in the maintenance of the systemic BP in a normotensive state. There were no significant differences between the Zn-deficient diet group and the standard diet group in the normotensive state. eNOS expression and Cu/Zn SOD activity in the aorta were also intact in Zn-deficient normotensive rats. These findings suggest that the 4 wk of Zn deficiency was inadequate to alter systemic blood pressure and focal NO signaling in the normotensive state. Long-term Zn deficiency affects the neuronal, immune, and hematopoietic systems, which contribute to systemic and/or local circulation. However, Zn deficiency alone does not cause hypertension and local vascular dysfunction in the normotensive state.     

Moderate zinc deficiency negatively affects biomechanical properties of rat tibiae independently of body composition

To guide development of novel nutritional strategies aimed at reducing the incidence of stress fractures, we observed the effects of manipulating dietary zinc (Zn) content on bone integrity in Sprague–Dawley rats fed either a severely Zn-deficient (ZnD; 1 ppm), a moderately Zn-deficient (MZnD; 5 ppm) or a Zn-adequate (ZnAD; 30 ppm) diet for 6 weeks. At the completion of the diet period, body composition, bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) were determined in vivo by using dual-energy X-ray absorptiometry. Following euthanasia, long bones were collected for determination of Zn content and biomechanical strength testing. Despite significant positive correlations between dietary Zn and both body weight (BW) and bone Zn content for the entire cohort (r=.77 and r=.83, respectively), rats fed MZnD or ZnAD diets did not differ in feed intakes, body composition, BMC, BA, BMD or BW. Tibial bones, but not femur bones, appear to be more responsive to dietary Zn manipulation, as all bone biomechanical strength indices in the ZnAD-fed rats were significantly greater than in rats fed the ZnD diets. Rats fed either MZnD or ZnAD diets had stronger tibiae (129% increase in maximum load and stress at maximum load, P<.01) compared with those fed ZnD diets. The load at breakage for the tibial bones of rats fed MZnD diets was not different from the ZnD rats, but lower (P<.05) than that of the ZnAD rats. These results suggest that since feed intakes, body composition, BMC, BA, BMD and BW were not significantly different between the MZnD- and ZnAD-fed animals, the reduced bone integrity observed in the MZnD-fed rats resulted from dietary Zn inadequacy, and not as a result of the reduced growth that is typically associated with Zn deficiency.     

Lipid peroxidation in mitochondria and microsomes from adult and fetal rat tissues

Pregnant female Wistar rats that received a control (100 ppm Zn) or a Zn-deficient diet (1.5 ppm Zn) from d 0 to 21, or nonpregnant normally fed female rats without or with five daily oral doses of 300 mg/kg salicylic acid were used for the experiments. In isolated mitochondria or microsomes from various maternal and fetal tissues, lipid peroxidation was determined as malondialdehyde formation measured by means of the thiobarbiturate method. Zn deficiency increased lipid peroxidation in mitochondria and microsomes from maternal and fetal liver, maternal kidney, maternal lung microsomes, and fetal lung mitochondria. Lipid peroxidation in fetal microsomes was very low. Zn deficiency produced a further reduction of lipid peroxidation in fetal liver microsomes. Salicylate increased lipid peroxidation in liver mitochondria and microsomes after addition in vitro and after application in vivo. The increase of lipid peroxidation by salicylate may be caused by two mechanisms: an increased cellular Fe uptake that, in turn, can increase lipid peroxidation and chelating Fe, in analogy to the effect of ADP in lipid peroxidation. The latter effect of salicylate is particularly expressed at increased Fe content.     

Subcellular distribution of protein kinase C (pKC) in erythrocytes and concentration ofd-myo-inositol-1,4,5-trisphosphate (IP3) in platelets and monocytes of force-fed zinc-deficient rats

The purpose of the present study was to investigate whether alimentary zinc (Zn) deficiency affects the activities of the Zn metalloenzymes protein kinase C (pKC) and the phosphatidylinositol-specific phospholipase C (PLC) in force-fed Zn-deficient rats. The in vivo activity of pKC was determined by measuring the subcellular distribution of the enzyme between the cytosolic and the particulate fraction of erythrocytes, whereas the activity of PLC was measured indirectly through the concentration of its metabolite inositol-1,4,5-trisphosphate (IP₃) in platelets and monocytes. For this purpose, 24 male Sprague-Dawley rats with an average live mass of 126 g were divided into 2 groups of 12 animals each. The Zn-deficient and the control rats received a semisynthetic casein diet with a Zn content of 1.2 and 24.1 ppm, respectively. All animals were fed the same amount of the diet (10.8 g dry matter [DM]/d and rat) four times daily by gastric tube. After 12 d, the depleted rats were in a state of severe Zn deficiency, as demonstrated by a 70% lower Zn concentration and a 66% reduction in the serum activity of alkaline phosphatase. The radioimmunologically determined concentration of IP₃ was reduced by a significant 55% in the platelets of the Zn-deficient rats (8.4 pmol IP₃/5·10⁸) as compared with the control rats (18.8 pmol IP₃/5·10⁸), whereas the IP₃ concentration in the monocytes was not affected by the alimentary Zn supply (1.4 vs 1.2 pmol IP₃/10⁶), nor was there any difference between the Zn-deficient and the control rats with regard to the radioenzymatically determined specific activity of pKC, either in the cytosolic fraction (32.7 vs 32.5 pmol P/min/mg protein) or in the particulate fraction (38.1 vs 36.5 pmol P/min/mg protein) of the erythrocytes.     

Elevation of hepatic levels of metallothionein and zinc in mice bearing experimental tumors.

A tumor growth-dependent elevation in the hepatic levels of Zn and metallothionein (MT), without a change in the level of Cu, was found in mice and rats bearing solid tumors in the inguinal region. The levels of Zn and MT thus elevated gave a significant correlation (r = 0.95) between them. Nevertheless, when tumor-bearing mice and rats were fed a Zn-deficient diet, the hepatic levels of Zn and MT did not increase. In mice in which inflammation was induced at the same region, on the other hand, hepatic levels of Zn and MT increased transiently after the injection of turpentine or carrageenan even when they were fed the Zn-deficient diet. These results suggest that the elevation of MT and Zn levels can be a helpful marker for detecting malignancy.     

Effects of dietary zinc levels on the activities of enzymes, weights of organs, and the concentrations of zinc and copper in growing rats

Zinc (Zn) is an essential nutrient that is required in humans and animals for many physiological functions, including immune and antioxidant function, growth, and reproduction. The present study was performed to investigate the effects of three Zn levels, including Zn adequate (35.94 mg/kg, as a control), Zn deficiency (3.15 mg/kg), and Zn overload (347.50 mg/kg) in growing male rats for 6 wk. This allowed for evaluation of the effects that these Zn levels might have on body weight, organ weight, enzymes activities, and tissues concentrations of Zn and Cu. The results showed that Zn deficiency has negative effects on growth, organ weight, and biological parameters such as alkaline phosphatase (ALP) and Cu−Zn superoxide dismutase (Cu−Zn SOD) activities, whereas Zn overload played an effective role in promoting growth, improving the developments of organs and enhancing immune system. Hepatic metallothionein (MT) concentration showed an identical increase tendency in rats fed both Zn-deficient and Zn-overload diets. The actual mechanism of reduction of Cu concentration of jejunum in rats fed a Zn-overload diet might involve the modulation or inhibition of a Cu transporter protein by Zn and not by the induction of MT.     

Activity and subcellular distribution of protein kinase C (PKC) in muscle and brain of force-fed zinc-deficient rats

The purpose of the present study was to investigate, in force-fed rats, whether alimentary zinc (Zn) deficiency affects the activity of the Zn-metalloenzyme protein kinase C (PKC). The in vivo activity of PKC was determined by measuring the subcellular distribution of the enzyme between the cytosolic and the particulate fraction in brain and muscle. For this purpose, 24 male Sprague-Dawley rats with an average live mass of 126 g were divided into 2 groups of 12 animals each. The Zn-deficient and the control rats received a semisynthetic casein diet with a Zn content of 1.2 and 24.1 ppm, respectively. All animals were fed four times daily by gastric tube in order to ensure that the depleted animals also received adequate nutrients and to synchronize the feed intake exactly. After 12 d, the depleted rats were in a state of severe Zn deficiency, as demonstrated by a 70% lower serum Zn concentration and a 66% reduction in the serum activity of alkaline phosphatase. Neither the cytosolic nor the particulate fraction of the thigh muscle showed any difference between the depleted and the control animals as regards PKC activity/g of muscle. The specific activity of PKC/mg of protein in the cytosolic fraction of the muscle was not affected by alimentary zinc deficiency, whereas the specific activity of PKC in the particulate fraction of the muscle was reduced by a significant 10% in Zn deficiency (150±12 vs 135±14 pmol P/min/mg protein). In the brain, neither the cytosolic nor the particulate fraction revealed any difference in PKC activity/g of fresh weight or in the specific activity/mg of protein between the control and the Zn-deficient rats.     

化瘀解毒中药抑制梗阻性肾病巨噬细胞浸润减轻炎性损伤的作用

为观察化瘀解毒中药对梗阻性肾病巨噬细胞浸润的影响及作用机制。将48只健康雄性Wistar大鼠随机分为假手术组、模型组、依普利酮组、中药组,每组12只。除假手术组外,其余大鼠结扎单侧输尿管(UUO)复制肾间质纤维化动物模型。治疗组分别给以依普利酮(100 mg/kg/d加入饲料喂养)和化瘀解毒中药煎剂(14 g/kg/d灌胃)。10 d后摘取肾脏,观察大鼠肾脏组织病理改变。免疫组化法标记巨噬细胞浸润,免疫组化、Western Blot方法检测血清和糖皮质激素诱导蛋白激酶1(SGK-1)、单核细胞趋化蛋白-1(MCP-1)、白细胞介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)的表达。肾脏病理显示,UUO组大鼠肾脏有明显的肾小管扩张及上皮细胞脱落,间质巨噬细胞浸润增多和细胞外基质(ECM)大量积聚,SGK-1、MCP-1、IL-1、TNF-α表达明显增强。化瘀解毒中药可明显减轻UUO大鼠肾脏巨噬细胞等炎性细胞浸润和ECM沉积,下调SGK-1、MCP-1、IL-1、TNF-α表达。以上结果说明化瘀解毒中药可抑制梗阻性肾病诱导的巨噬细胞浸润,减轻肾脏炎性损伤。     

Influence of alimentary zinc deficiency on the concentration of the second messengers D-myo-inositol-1,4,5-trisphosphate (IP3) and s,n-1,2-diacylglycerol (DAG) in testes and brain of force-fed rats

The phosphatidylinositol-specific phospholipase C, presumably a Zn-metalloenzyme, catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to inositol-1,4,5-trisphosphate (IP₃) and s,n-1,2-diacylglycerol (DAG). The activity of phosphatidylinositol-specific phospholipase C was measured indirectly by determination of the metabolites IP₃ and DAG in Zn deficiency. For this purpose 24 male Sprague-Dawley rats with an average live mass of 117 g were divided into 2 groups of 12 animals each. The Zn-deficient and the control group received a semisynthetic casein diet with a Zn content of 1.6 ppm and 115 ppm, respectively. In order to prevent the reduced feed intake that occurs in Zn deficiency and the associated energy and protein depletion from interfering with the experimental parameters, all animals were fed four times daily by gastric tube. This made it possible to supply all animals with adequate nutrients and to synchronize the feed intake exactly. After 12 d, the depleted rats were in a severe state of Zn deficiency, as demonstrated by the reduction of Zn in the serum and the femur by 74% and 43%, respectively, and the 28% lower serum activity of alkaline phosphatase. The radioimmunologically determined concentrations of IP₃ were reduced by a significant 53% in the testes of the Zn-deficient rats (0.24 nmol IP₃/g wet wt) compared to the control animals (0.51 nmol IP₃/g wet wt), while the IP₃ concentration in the brain was not affected by the alimentary Zn supply (1.7 and 1.6 nmol IP₃/g wet wt, respectively). The DAG concentrations in the testes (474 vs 471 nmol DAG/g wet wt) and the brain (594 vs 640 nmol DAG/g wet wt), which were determined by radioenzymatic methods, showed no significant differences in relation to the alimentary Zn supply. The fact that the Zn concentration in the Zn-deficient rats was reduced only in the testes and not in the brain and that high concentrations of DAG may also result from other metabolic processes suggests that the phosphatidylinositol-specific phospholipase C in the mammalian organism is a Zn-metalloenzyme whose activity is reduced in alimentary Zn deficiency in tissues suffering Zn loss.     

Bone marrow–derived mesenchymal stem cells attenuate tubulointerstitial injury through multiple mechanisms in UUO model

Current evidence supports the use of bone marrow–derived mesenchymal stem cells (MSCs) for a diverse range of clinical applications, and many studies have shown that MSCs have renal-protective effects, but the mechanism is not well understood. Therefore, in this study, we aim to further identify whether MSCs can attenuate renal fibrosis by decreasing tubulointerstitial injury in a unilateral ureteral obstruction (UUO) model. In this study, we cultured MSCs and then transplanted them into a UUO model through the tail vein. Histology, cell proliferation, peritubular capillary (PTC) loss and myofibroblast markers were examined on days 3, 7 and 14 after surgery. We demonstrated that renal interstitial fibrosis in the MSC group was significantly attenuated compared with the UUO and DMEM groups. Moreover, MSC treatment inhibited the loss of PTCs and increased parenchymal cell proliferation. In addition, UUO-induced activation and proliferation of myofibroblasts were suppressed by MSC infusion. Furthermore, MSCs attenuated tubulointerstitial infiltration of macrophages in UUO mice. Tubulointerstitial damage plays a very important role in the progression of chronic kidney disease (CKD). PTC loss, macrophage recruitment, and myofibroblast activation are directly correlated with the development of renal tubulointerstitial fibrosis. Our results suggest that MSC infusion in the UUO model is a promising therapeutic strategy for promoting kidney repair.     

Changes in hypothalamic noradrenergic systems during the anorexia of zinc deficiency

Pregnant Wistar rats fed control and Zn-deficient diets received daily oral doses of 0, 100, and 300 mg/kg sodium valproate from d 16 to 20 of gestation. Only the highest valproate doses induced a small reduction in fetal body weight in the normally fed group. Zinc deficiency caused a drastic reduction in maternal and only a small reduction in fetal serum Zn concentrations. Valproate treatment had no effect on maternal and fetal serum Zn concentrations. Valproate reduced fetal liver Zn content only in the normally fed group. The reduction of liver Zn content resulted from the reduction of Zn-metallothionein. Valproate did not affect total Zn and Zn-metallothionein in kidneys. Three percent of the Zn-deficient fetuses developed hydronephrosis and hydrops. Valproate treatment drastically enhanced the occurrence of fetal hydronephrosis and hydrops. Valproate induced fetal liver necroses, independent of Zn nutrition.     

Cerebroside sulfotransferase deficiency ameliorates L-selectin-dependent monocyte infiltration in the kidney after ureteral obstruction

Mononuclear cells infiltrating the interstitium are involved in renal tubulointerstitial injury. The unilateral ureteral obstruction (UUO) is an established experimental model of renal interstitial inflammation. In our previous study, we postulated that L-selectin on monocytes is involved in their infiltration into the interstitium by UUO and that a sulfated glycolipid, sulfatide, is the physiological L-selectin ligand in the kidney. Here we tested the above hypothesis using sulfatide- and L-selectin-deficient mice. Sulfatide-deficient mice were generated by gene targeting of the cerebroside sulfotransferase (Cst) gene. Although the L-selectin-IgG chimera protein specifically bound to sulfatide fraction in acidic lipids from wild-type kidney, it did not show such binding in fractions of Cst(-/-) mice kidney, indicating that sulfatide is the major L-selectin-binding glycolipid in the kidney. The distribution of L-selectin ligand in wild-type mice changed after UUO; sulfatide was relocated from the distal tubules to the peritubular capillaries where monocytes infiltrate, suggesting that sulfatide relocated to the endothelium after UUO interacted with L-selectin on monocytes. In contrast, L-selectin ligand was not detected in Cst(-/-) mice irrespective of UUO treatment. Compared with wild-type mice, Cst(-/-) mice showed a considerable reduction in the number of monocytes/macrophages that infiltrated the interstitium after UUO. The number of monocytes/macrophages was also reduced to a similar extent in L-selectin(-/-) mice. Our results suggest that sulfatide is a major L-selectin-binding molecule in the kidney and that the interaction between L-selectin and sulfatide plays a critical role in monocyte infiltration into the kidney interstitium.     

Elevated dietary salt suppresses renin secretion but not thirst evoked by arterial hypotension in rats

Increased dietary salt intake was used as a nonpharmacological tool to blunt hypotension-induced increases in plasma renin activity (PRA) in order to evaluate the contribution of the renin-angiotensin system (RAS) to hypotension-induced thirst. Rats were maintained on 8% NaCl (high) or 1% NaCl (standard) diet for at least 2 wk, and then arterial hypotension was produced by administration of the arteriolar vasodilator diazoxide. Despite marked reductions in PRA, rats maintained on the high-salt diet drank similar amounts of water, displayed similar latencies to drink, and had similar degrees of hypotension compared with rats maintained on the standard diet. Furthermore, blockade of ANG II production by an intravenous infusion of the angiotensin-converting enzyme inhibitor captopril attenuated the hypotension-induced water intake similarly in rats fed standard and high-salt diet. Additional experiments showed that increases in dietary salt did not alter thirst stimulated by the acetylcholine agonist carbachol administered into the lateral ventricle; however, increases in dietary salt did enhance thirst evoked by central ANG II. Collectively, the present findings suggest that hypotension-evoked thirst in rats fed a high-salt diet is dependent on the peripheral RAS despite marked reductions in PRA.     

Effects of Zinc Supplementation and Deficiency on Bone Metabolism and Related Gene Expression in Rat

One hundred male rats were randomly divided into four groups (n = 25) and fed a Zn-adequate diet (ZA, 46.39 mg/kg), Zn-deficient diet (ZD, 3.20 mg/kg), Zn-overdose diet (ZO, 234.39 mg/kg), or were pair-fed a Zn-adequate diet (PF) for 5 weeks, respectively. The body weight, femur weight, and activity of alkaline phosphatase (ALP) were reduced in the ZD group but were increased in the ZO group. Zn concentrations in both liver and femur were elevated in the ZO group, whereas femur Zn was decreased in the ZD group. The concentrations of calcium and phosphorus were lower in the ZD than those in other groups. Serum calcium concentration was decreased in the ZD. The relative expression level of ALP was decreased in both ZD and PF, and no significant differences were observed between ZO and ZA. Insulin-like growth factor-I (IGF-I) mRNA level was reduced in the ZD but unchanged in the ZO and PF group. Zn deficiency also decreased ALP mRNA level as compared with that of PF group. Carbonic anhydrase II mRNA level was not affected by Zn. Nevertheless, dietary Zn influenced the growth, bone metabolism, and expression of IGF-I and ALP in male growing rats.