Triiodothyronine administration reverses vitamin A deficiency-related hypo-expression of retinoic acid and triiodothyronine nuclear receptors and of neurogranin in rat brain

Recent studies have revealed that retinoids play an important role in the adult central nervous system and cognitive functions. Previous investigations in mice have shown that vitamin A deficiency (VAD) generates a hypo-expression of retinoic acid (RA, the active metabolite of vitamin A) receptors and of neurogranin (RC3, a neuronal protein involved in synaptic plasticity) and a concomitant selective behavioural impairment. Knowing that RC3 is both a triiodothyronine (T3) and a RA target gene, and in consideration of the relationships between the signalling pathways of retinoids and thyroid hormones, the involvement of T3 on RA signalling functionality in VAD was investigated. Thus, the effects of vitamin A depletion and subsequent administration with RA and/or T3 on the expression of RA nuclear receptors (RAR, RXR), T3 nuclear receptor (TR) and on RC3 in the brain were examined. Rats fed a vitamin A-deficient diet for 10 weeks exhibited a decreased expression of RAR, RXR and TR mRNA and of RC3 mRNA and proteins. RA administration to these vitamin A-deficient rats reversed only the RA hypo-signalling in the brain. Interestingly, T3 is able to restore its own brain signalling simultaneously with that of vitamin A and the hypo-expression of RC3. These results obtained in vivo revealed that one of the consequences of VAD is a dysfunction in the thyroid signalling pathway in the brain. This seems of crucial importance since the down regulation of RC3 observed in the depleted rats was corrected only by T3.     

Decreases in bone mineral content by dietary all-trans retinoic acid precede decreases in bone mineral density in a weanling rat model of cigarette smoke-induced lung injuries

Research has indicated that excessive vitamin A can have deleterious impacts on bone. Retinoic acid (RA), the most active metabolite of vitamin A, has been tested in clinical trials for treatment of lung cancer and emphysema. These trials are not measuring Bone Mineral Content (BMC) or Bone Mineral Density (BMD). In this study, we used an animal model to determine potential deleterious effects of all-trans RA on bone mass when used as a means to protect against or treat cigarette smoke-induced lung injuries, and also to evaluate BMC as a potential early indicator of osteoporosis risk. Twenty-four male weanling rats were fed either a control diet or a RA-supplemented diet. Half of each group was exposed to 40 cigarettes per day, 5 days per week, for 4 weeks. BMC and BMD were measured at weeks 2 and 4. RA supplementation in all groups significantly decreased (p < 0.05) only BMC at week 2 and both BMC and BMD (both p < 0.05) at week 4. The same results were observed when BMC was expressed relative to body weight. These data suggest that caution should be used when RA is used to treat smoke-related lung injuries.     

Lung retinyl ester is low in young adult rats fed a vitamin A deficient diet after weaning, despite neonatal vitamin A supplementation and maintenance of normal plasma retinol

Although it is understood that plasma retinol concentration is not proportional to the concentration of vitamin A stored in liver, plasma retinol still is often used as an indicator of vitamin A status. An aim of vitamin A supplementation strategies is to maintain plasma retinol concentration in a range considered adequate, generally >1.05 micromol/L in humans, with some adjustment for age. In the present study in rats, we addressed the following question: Does lung vitamin A increase postnatally, as is observed in rats fed a vitamin A-adequate diet, if plasma retinol is maintained at approximately 1 micromol/L by supplementation at neonatal age, but the weaning diet is deficient in vitamin A? We treated rats on postnatal d 6, 7, and 8 with placebo (oil), vitamin A, retinoic acid (RA), and a nutrient-metabolite combination of vitamin A and RA, VARA, after which tissues were analyzed on d 9. Other rats treated identically as neonates were fed a vitamin A-deficient diet from 3-9 wk of age, and in parallel, another group of rats was fed a vitamin A-adequate diet. Although supplementation with vitamin A or VARA elevated liver and lung retinyl esters (RE) on d 9 (P < 0.0001), and prevented the fall in plasma retinol to <1 micromol/L by 9 wk of age, when the diet was vitamin A-deficient, lung RE fell to 28% of the concentration present in the lungs of rats fed the vitamin A-adequate diet (P < 0.0001). We infer that the lungs depend, at least in part, on the uptake of dietary vitamin A, probably from chylomicrons, to develop RE stores in the postweaning growth period.     

Effect of dietary retinoic acid on circulatory vitamin A homeostasis in polybrominated biphenyl-treated rats

Retinoic acid (RA) supplementation is known to lower the amount of retinol in circulation. In contrast, the feeding of polyhalogenated aromatic hydrocarbons results in an elevated level of circulatory retinol. We investigated the effect of short-term dietary exposure to RA on the amount of serum retinol in female Sprague-Dawley rats fed either a basal diet (control rats) or the basal diet containing 100 mg of polybrominated biphenyls (PBBs)/kg diet (PBB-treated rats). After feeding of the above diets for 137 d, RA (12 mg/kg diet) was included in both the control and PBB-containing diets. The rats were fed the RA-containing diet for 3 d and then killed (d 140). Blood samples were obtained before and after RA treatment. Chronic PBB treatment of rats resulted in lower hepatic vitamin A and higher kidney vitamin A than in control rats. Serum retinol concentration was significantly higher in rats treated with PBB for 137 d than in controls; the subsequent treatment with RA lowered serum retinol to a level that was not different from that of control rats treated with RA. Our observations agree with earlier findings that 1) PBB treatment alters vitamin A homeostasis, and 2) dietary RA lowers the amount of circulatory retinol. An important new observation is that serum retinol homeostasis in PBB-treated rats appears to be regulated by a mechanism similar to that of normal rats. Polyhalogenated aromatic hydrocarbons may thus be useful tools to study the control mechanisms of vitamin A homeostasis.     

Evidence for two subcellular pools and different kinetic behaviour of retinyl palmitate in rat liver

Rats were fed vitamin A deficient diets (-A) or supplemented with vitamin A (+A) (4.4 mg retinol equivalents/kg diet), either without (-RA) or with retinoic acid (+RA) (12 mg/kg diet) supplementation for up to six weeks. Plasma and liver levels as well as the subcellular localization of vitamin A were determined. In rats reared on the vitamin A rich diet the localization of retinyl palmitate (principal reserve form) is shown to be dependent on age. Two pools exist, i.e. one consisting of the nuclear and mitochondrial-lysosomal fractions and the other containing the microsomal and cytosol fractions. A rapid replenishment of mitochondrial-lysosomal fractions occurs in the first weeks after the weaning. During six weeks of deficient diet an identical mobilization was seen from the different subcellular fractions. Supplementation with RA caused an immediate and sustained reduction of serum vitamin A levels but did not disturb the subcellular localization of retinyl palmitate. A relationship between these phenomena and the subcellular distribution of the retinyl palmitate hydrolase (RPH) and the cellular vitamin A binding proteins (CRBP) is likely to exist.     

维生素A缺乏对幼鼠脑发育和学习记忆的影响

目的 :　探讨维生素 A缺乏 ( VAD)对幼鼠脑发育和学习记忆能力的影响。方法 :　建立 VAD母鼠及其子代幼鼠模型。观察子代幼鼠生长发育情况 ,并测定 7w龄幼鼠学习记忆能力 ,海马和皮层蛋白质含量、细胞增殖周期及海马神经细胞超微结构改变。结果 :　 ( 1 ) VAD组幼鼠体重增长明显慢于对照组 ;( 2 ) VAD组幼鼠学习次数明显多于对照组 ( P<0 .0 5 ) ,记忆时间明显短于对照组 ( P<0 .0 1 ) ;( 3) VAD组幼鼠海马及皮层蛋白质含量显著低于对照组 ( P<0 .0 1 ) ;( 4 )VAD组幼鼠海马和皮层细胞增殖指数 ( PI)明显高于对照组 ( P<0 .0 1 ) ;( 5 ) VAD组幼鼠海马锥体细胞之间突触联系数量减少 ,突触内突触小泡减少 ,星形胶质细胞增多 ,且有固缩变性。结论 :　VAD会导致幼鼠脑发育受损和学习记忆能力下降。     

边缘性维生素A缺乏及干预对幼鼠海马神经元形态与功能的影响

目的了解胚胎期开始的边缘缺乏(MVAD)对幼鼠海马神经元的形态及功能造成的损害,以及从新生儿期开始维生素A干预,能否使这种损害得以恢复。方法 11只健康母鼠于交配前3 w开始喂饲含VA 400 IU/kg的MVAD饲料,随机抽取其子鼠19只于断乳后继续喂饲同样的MVAD饲料为VAD组。另外随机抽取13只子鼠于出生0 d开始喂饲其母鼠含VA 6500 IU/kg的正常饲料,断乳后继续饲正常饲料为干预(VAI)组。随机抽取7只健康母鼠的10只子鼠作为正常对照(control,C)组,其饲料为含VA 6500 IU/kg的正常饲料。各组幼鼠均于7 w龄处死。用高效液相色谱法(HPLC)检测血清VA浓度。对海马切片进行HE染色,了解其神经元形态及细胞核大小的改变。运用电生理技术检测幼鼠离体海马脑片CA1区长时程增强(LTP),并在VAD组人工脑脊液(ACSF)中直接加入视黄酸(RA)后检测LTP。用透射电镜观察强直刺激前后,海马CA1区突触超微结构的变化。结果 MVAD孕鼠交配时血清VA浓度明显低于对照组。VAD组血清VA浓度明显低于C组,VAI组的血清VA浓度低于C组水平,但明显高于VAD组。海马CA1区锥体细胞层神经元细胞核的面积,VAD组明显小于C组,VAI组大于VAD组,与C组比较无明显差别。C组海马CA1区群峰电位增长幅度明显大于VAD组,VAI组小于C组,大于VAD组(P<0.05);VAD组脑片的ASCF中加入RA,其群峰电位增长幅度由(22.86±3.26)%上升到(59.08±7.22)%(P<0.01),与C组无显著差异。强直刺激后的C组与空白对照组(BC)比较,其海马CA1区突触的活性区长度和突触后致密物(PSD)厚度均明显增加,突触界面模拟圆半径明显减小,突触间隙宽度没有明显差异;强直刺激后,C组突触活性区长度明显大于VAD组,与VAD+RA组比较无显著差异,C组和VAD+RA组的突触界面模拟圆半径小于VAD组。结论 MVAD可导致少量CA1区神经元缺失和坏死,并减小了海马神经元细胞核的面积。同时直接影响海马神经元LTP的诱发,以及减小了LTP诱发后突触超微结构变化的程度。新生儿期开始的VAI可使MVAD对海马神经元的影响得到部分恢复。     

Effects of retinoic acid on hepatic cytochrome P-450 dependent enzymes in rats under different vitamin A status

The temporal effects of retinoic acid supplementation on hepatic cytochrome P-450-dependent enzymes were studied on the rat. Four groups of male weanling rats were fed semi synthetic diets: two groups containing 0 or 4.4 mg retinol equivalents per kg diet as retinyl palmitate (A- RA- and A+ RA- groups) and two similar groups supplemented with all trans retinoic acid (12 mg/kg diet) (A- RA+ and A+ RA+ groups). After five or ten weeks of feeding, the rats were killed, liver microsomes were prepared and assayed for aniline hydroxylase, aminopyrine N demethylase activities and cytochrome P-450 levels. Whereas no change was observed between the four groups after 5 weeks, the following modifications appeared after 10 weeks: Vitamin A deficiency decreased hepatic drug metabolism by phase I enzymes (hydroxylase and N demethylase) but only when liver storage pool was not detectable. Vitamin A concentration as low as 4 micrograms/g is sufficient to avoid any perturbation of these enzymes. Parallel to a sparing effect on liver reserves of vitamin A, retinoic acid maintained a normal activity of enzymes of xenobiotic metabolism. However, retinoic acid treatment produced an alteration of phase I enzymes in vitamin A supplemented group (A+ RA+). As this was accompanied by a doubling of vitamin A liver reserves, compared to A+ RA- group, it is suggested that this might result from a liver vitamin A overloading, leading to membrane damage perturbing microsomal enzymes. These results indicate the need for a more careful use of retinoids as a therapeutic agent.     

维生素A缺乏对初生大鼠脑发育的影响

目的 :　探讨维生素 A缺乏 (VAD)对初生大鼠脑发育的影响及其分子生物学机制。方法 :　建立不同程度 VAD母鼠模型。仔鼠出生后测定其血清维生素 A(VA)水平、脑组织 VA含量、体重、脑重、脑组织蛋白质含量、脑细胞增殖周期和脑内视黄酸受体 α、β(RARα、RARβ)、视黄醇X受体 β(RXRβ)和多巴胺受体 - 2 (D2 R) m RNA表达。结果 :　 (1 )初生鼠血清 VA水平和脑组织VA含量三组间有显著性差异 (P<0 .0 1 ) ,重度维生素 A缺乏 (SVAD)组明显低于对照组和边缘型维生素 A缺乏 (MVAD)组 ,MVAD组也明显低于对照组。 (2 ) SVAD组初生鼠体重和脑重明显低于对照组和 MVAD组 (P<0 .0 1 ) ,MVAD组与对照组相比无显著性差异。 (3 )全脑蛋白质含量、每克脑组织蛋白质含量和脑细胞增殖指数 (PI) SVAD组均明显低于对照组 (P<0 .0 1 ) ,MVAD组仅全脑蛋白质含量明显低于对照组 (P<0 .0 1 ) ,其它指标与对照组相比也有降低但无统计学意义。(4)脑细胞 RARα、RARβ、RXRβ 和 D2 R m RNA表达 SVAD组仅 RARα和 D2 R有微弱表达 ,MVAD组与对照组相比除 RARβ外均有不同程度降低。结论 :　VAD会导致初生大鼠脑发育受损 ,其作用可能是通过降低脑细胞内视黄酸受体表达而产生的     

Vitamin A in reproduction and development

The requirement for vitamin A in reproduction was first recognized in the early 1900's, and its importance in the eyes of developing embryos was realized shortly after. A greater understanding of the large number of developmental processes that require vitamin A emerged first from nutritional deficiency studies in rat embryos, and later from genetic studies in mice. It is now generally believed that all-trans retinoic acid (RA) is the form of vitamin A that supports both male and female reproduction as well as embryonic development. This conclusion is based on the ability to reverse most reproductive and developmental blocks found in vitamin A deficiency induced either by nutritional or genetic means with RA, and the ability to recapitulate the majority of embryonic defects in retinoic acid receptor compound null mutants. The activity of the catabolic CYP26 enzymes in determining what tissues have access to RA has emerged as a key regulatory mechanism, and helps to explain why exogenous RA can rescue many vitamin A deficiency defects. In severely vitamin A-deficient (VAD) female rats, reproduction fails prior to implantation, whereas in VAD pregnant rats given small amounts of carotene or supported on limiting quantities of RA early in organogenesis, embryos form but show a collection of defects called the vitamin A deficiency syndrome or late vitamin A deficiency. Vitamin A is also essential for the maintenance of the male genital tract and spermatogenesis. Recent studies show that vitamin A participates in a signaling mechanism to initiate meiosis in the female gonad during embryogenesis, and in the male gonad postnatally. Both nutritional and genetic approaches are being used to elucidate the vitamin A-dependent pathways upon which these processes depend.     

维生素A对SD大鼠食欲及下丘脑神经肽Y基因表达的影响

目的探讨维生素A对SD大鼠食欲和下丘脑神经肽Y基因表达的影响,初步探讨维生素A影响大鼠食欲的机制。方法将雄性SD大鼠随机分为2组:A组(维生素A缺乏组)和B组(对照组)。喂养74d,A组随机取出16只,分为2组:A1组(维生素A缺乏组)和A2组(维生素A皮下补充组);B组随机取出8只,为B1组(对照组)。实验79d,将这3组大鼠全部处死,取血和组织进行相关指标测定。A组剩余的动物按体重随机分为2组:A3组(维生素A缺乏组)和A4组(维生素A食物补充组)。B组剩余的8只动物为B2组(对照组)。30d后将其全部处死,取血和组织进行相关指标测定。结果维生素A缺乏组进食量显著低于正常对照组,给予缺乏组大鼠维生素A皮下和食物补充后,大鼠进食量显著增多。维生素A缺乏组下丘脑神经肽YmRNA表现为低表达,皮下补充维生素A后大鼠下丘脑神经肽YmRNA的表达水平明显升高。结论维生素A影响大鼠食欲的可能机制是改变了下丘脑有关控制食欲的基因表达。     

Marginal vitamin A deficiency in pigs experimentally infected with Trichuris suis: a model for vitamin A inadequacy in children.

The development of an experimental model for marginal vitamin A deficiency in humans is of major interest, enabling the elucidation of possible interactions with helminth infections. We established a useful experimental model for human vitamin A deficiency in young pigs; deficiency was induced through a depletion method encompassing both sow and offspring. We report on a 2 x 2 study in which 18-week-old vitamin A deficient pigs and vitamin A sufficient littermates were infected with both of the intestinal nematodes Trichuris suis and Ascaris suum and followed for 14 weeks through 32 weeks of age. Forty-nine pigs were followed with respect to bodyweight, liver biopsies and blood samples for retinol concentration and faecal samples for parasite eggs and worms. Liver and serum concentrations of vitamin A were significantly diminished in the vitamin A deficient (VAD) group as compared to the vitamin A sufficient (VAS) group both before (P < 0.001) and after inoculation with T. suis and A. suum (P < 0.02). A significant correlation between retinol content in micro-biopsy needle samples and gross liver content was found (r = 0.457, n = 48, P = 0.001). The adult T. suis worms in the VAD group were marginally smaller (36.7 vs 40.2 mm; P = 0.08), more orally located (section 2.9 vs 3.9; P = 0.08) and had a higher proportion of males (0.58 vs 0.50; P = 0.08) whereas there were no effects of diet treatment on fecundity. The proportion of pigs with faecal T. suis egg excretion 12 weeks post inoculation (p.i.) was significantly lower in the VAD group compared with the VAS infected group (21 vs 78%; P = 0.036). In addition, faecal T. suis egg excretion was significantly lower in the VAD group at both week 11 (P = 0.040) and week 12 p.i. (P = 0.021). Vitamin A deficiency may have altered the functional integrity of the mucosal intestinal epithelium, disrupting the normally delicate attachment of T. suis and leading to the premature termination of infection. However, a possible antagonistic interaction, if verified, should not preclude interventions to improve vitamin A status, i.e., treatment should accompany anthelmintic treatment.     

Effects of dietary vitamin A deficiency, retinoic acid and protein quantity and quality on serially obtained plasma and liver levels of vitamin A in rats.

Rats were fed vitamin A-deficient diets either alone, supplemented with retinoic acid (RA), or of limited protein quality or quantity (7%rice or 7% casein protein); one group was fed 7% rice protein supplemented with vitamin A. Plasma and liver levels of vitamin A were determined serially. Plasma levels in rats fed otherwise adequate vitamin A-deficient diets remained above 30 micrograms/dl until liver reserves were below 10 micrograms/g tissue, at which point plasma levels decreased in some but not all rats while liver levels continued to decline (at a slower rate) to levels as low as 3 micrograms/g. Supplementation with RA caused an immediate and sustained reduction of 15 to 20 micrograms/dl in circulating vitamin A. At 7% dietary protein, plasma levels of vitamin A remained above 30 micrograms/dl when casein protein was fed or when the rice protein diet was supplemented with dietary vitamin A, but not when the rice protein diet was fed without an exogenous source of the vitamin. A scheme is proposed suggesting possible regulatory mechanisms that might control homeostatic levels of plasma vitamin A.     

Cortical and trabecular bone, bone mineral density, and resistance to ex vivo fracture are not altered in response to life-long vitamin A supplementation in aging rats

High vitamin A (VA) intakes have been correlated with increased risk of bone fracture. Over 50% of the U.S. adult population reports use of dietary supplements, which can result in VA intakes > 200% of the RDA. In this study, 2 experiments were designed to determine the effect of dietary VA on cortical and trabecular bone properties and resistance to ex vivo fracture. In Expt. 1, we investigated whether orally administered VA accumulates in bone. Seven-week-old rats were treated daily with VA (6 mg/d for 14 d). Total retinol increased in both the tibia and femur (P < 0.01). In Expt. 2, we conducted a longitudinal study in which rats were fed 1 of 3 levels of dietary VA (marginal, adequate, and supplemented, equal to 0.35, 4, and 50 μg retinol/g diet, respectively) from weaning until the ages of 2-3 mo (young), 8-10 mo (middle-age), and 18-20 mo (old). Tibial trabecular and cortical bone structure, bone mineral density, and resistance to fracture were measured using micro-computed tomography and material testing system analysis, respectively. The VA-marginal diet affected measures of cortical bone dimension, suggesting bone remodeling was altered. VA supplementation increased medullary area and decreased cortical thickness in young rats (P < 0.05), but these changes were not present during aging. VA supplementation did not affect resistance to fracture or bone mineral content in old rats. From these results, we conclude that VA-marginal status affects trabecular bone more than cortical bone, and VA supplementation at a moderate level over the lifetime is unlikely to increase the risk of age-related bone fracture in rats.     

Age-related changes in sympathetic nervous activity of rats receiving vitamin E-deficient diet

To study the relationship between age-related stimulation of sympathetic nervous activity and vitamin E, excretion of urinary catecholamine and the contents of organ catecholamine were measured in rats receiving a vitamin E-deficient or control diet for 95 weeks. Rats exhibited about 95% hemolysis after 4 weeks on the vitamin E-deficient diet and this value remained the same for 95 weeks. alpha-Tocopherol in plasma was not detectable in the deficient diet-fed rats, and lipid peroxide concentrations in the plasma, liver and adrenal glands of rats receiving the vitamin E-deficient diet for 95 weeks were 3- to 30-fold higher than those of control rats. Urinary excretion of catecholamine (norepinephrine (NE), epinephrine (E) and dopamine (DA] increased with age. Excretion of NE in 24-h urine of rats receiving the vitamin E-deficient diet for 50 and 95 weeks was 2- to 3-fold higher than that of control rats, although no significant difference was observed at week 12. Contents of NE and E in the adrenal glands and of NE in the heart from the deficient rats were significantly lower than those of control rats at week 95. These results suggest that sympathetic nervous activity is enhanced in aged rats and that the sympathetic nervous activity in vitamin E-deficient rats is greater than in control rats.     

Bioavailability of vitamin D2 from irradiated mushrooms: an in vivo study

Vitamin D2 from irradiated edible mushrooms might present a possible dietary source of this vitamin, subject to its bioavailability. Having previously optimized a method for the conversion of ergosterol in mushrooms to vitamin D2, this paper examines the vitamin D-enriched mushrooms (Lentinula edodes) for their bioavailability of the vitamin, using an animal model. Thirty male Wistar rats were fed for 1 week with a diet deficient in vitamin D. After this 1-week period, six rats were randomly selected and killed for analysis of initial bone mineral density, and serum level of 25-hydroxyvitamin D. A group of twelve rats of the test animals received 1 mug of vitamin D2 from irradiated mushrooms for a period of 4 weeks until being killed. The remaining twelve rats were fed un-irradiated mushrooms at the same level to act as controls. At the end of a 4-week period, the mean serum 25-hydroxyvitamin D level of the experimental group was 129.42 (sd 22.00) nmol/l whereas it was only 6.06 (sd 1.09) nmol/l in the control group. Femur bone mineral density of the experimental group of animals was significantly higher (P<0.01) than the control group. In addition, serum Ca concentrations among groups were shown to be significantly higher (P<0.01). It may be concluded from the results that vitamin D2 from UV-irradiated mushrooms is well absorbed and metabolized in this model animal system. Significant increase in femur bone mineralization (P<0.01) was shown in the presence of vitamin D2 from irradiated mushrooms compared with the controls.     

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the uptake, distribution and excretion of a single oral dose of [11,12-3H]retinyl acetate and on the vitamin A status in the rat

TCDD (2,3,7,8-Tetrachlorodibenzo-p-dioxin, 10 micrograms/kg body weight, p.o.) was given to male Sprague-Dawley rats 4 d before the oral administration of a physiological dose of [11,12-3H]retinyl acetate (RA). The rats were kept in metabolic cages for up to 192 h after RA administration. Radioactivity and/or vitamin A were determined in tissues and excreta. TCDD-pretreated and control rats excreted 41 and 23%, respectively, of the radioactivity of RA during the 192 h after administration. In control animals, 30% of the radioactivity of RA entered the liver within 6 h, the stores reaching 42% after 192 h. Maximum storage in TCDD-treated rats was 13% and after 192 h only 9% of the dose remained. A lag period of 12-24 h preceded the TCDD-induced increase in renal (175-671%) and serum (85-145%) radioactivity. In TCDD-treated rats less radioactivity was found in the intestine (45-79% decrease) and adrenals (14-73% decrease). Relative to the total body content, significantly more radioactivity was found in the kidney, serum, testes and epididymis of TCDD-treated rats. The decrease in vitamin A content after TCDD-treatment was 39-53% in the liver, 19-67% in the intestine and 18-44% in the epididymis. The kidneys of TCDD-treated rats contained more vitamin A (3-30 times more). TCDD treatment initially increased (42%) and later decreased (40%) the vitamin A content in the thymus as compared to controls. Pretreatment with a single low dose of TCDD thus affects both storage and excretion of radioactivity from newly administered RA as well as the vitamin A content in several tissues.     

High dietary iron enhances oxidative stress in liver but does not increase aberrant crypt foci development in rats with low vitamin E status

The purpose of this study was to examine the effects of high-iron and low-vitamin E diets on lipid peroxidation and aberrant crypt foci (ACF) development in rats. In a 2 x 2 x 2 factorial design, male Sprague-Dawley rats were fed 45 or 450 mg Fe/kg diet (adequate and high iron, respectively) and 15 or 100 IU vitamin E/kg diet (low and adequate vitamin E, respectively) for three weeks, when they received saline or azoxymethane (15 mg/kg for 2 wk). Diets were continued for an additional six weeks. Serum alpha-tocopherol concentrations in rats fed low-vitamin E diets were decreased to 30% of concentrations observed in rats fed adequate-vitamin E diets (p < 0.0001). Also, serum alpha-tocopherol concentrations tended to be lower in rats supplemented with iron (p < 0.08). Lipid peroxidation in liver was significantly elevated by high-iron diets after 3 and 10 weeks of treatment, but lipid peroxidation in colonic mucosa was not altered by dietary iron or vitamin E. The total number of ACF and number of large ACF (> or = 4 aberrant crypts/focus) were not significantly altered by iron or vitamin E intakes. However, the size distribution of ACF was slightly altered, such that iron-supplemented rats had 12% more ACF with two crypts per focus (p < 0.02) than rats fed adequate-iron diets. Our data suggest that high-iron diets enhanced oxidative stress in liver, but not colon, of rats fed low-vitamin E diets. Furthermore, a high-iron diet does not increase the total number of ACF, even when vitamin E status is low.     

维生素A缺乏对肠粘膜细胞因子免疫应答的影响

目的研究维生素A缺乏(vitamin A deficiency,VAD)对大鼠肠粘膜细胞因子免疫应答的影响,探讨VAD降低粘膜免疫力的机制。方法在建立VAD大鼠模型的基础上,给予鼠伤寒沙门氏菌灌胃诱导肠道感染。取新鲜回肠组织,采用ELISA和RT-PCR法,从蛋白和基因水平测定IFN-γ、IL-2、IL-4、IL-6、IL-10和IL-12的变化。结果VAD大鼠肠粘膜主要由树突状细胞产生的细胞因子IL-12的表达显著增高,[蛋白(lg ng/g mucosal tissue)VA正常组4.07±0.15,VAD4.41±0.02,基因(lg copies/50ng total RNA)VA正常组4.99±0.18,VAD5.53±0.15,伴有肠道感染时IL-12的产生进一步升高,蛋白和基因两者分别为:4.59±0.15和5.78±0.26];Th1细胞因子:IFN-γ降低两者分别为蛋白:VA正常组3.15±0.34,VAD2.67±0.15;基因:VA正常组3.15±0.34,VAD2.67±0.15,和VA正常组5.36±0.26,VAD5.19±0.27,均(P<0.01);Th2细胞因子IL-4在肠道感染后显著降低(蛋白VAD组为2.29±0.13,VA正常组2.39±0.20),尤其是VAD大鼠IL-4水平更低(蛋白2.13±0.17);IL-6mRNA在肠道感染时都明显下降(感染后VA正常组5.45±0.3,感染后VAD组5.44±0.3,VA正常组5.85±0.31)(P<0.01),IL-10mRNA在未感染VAD大鼠也降低(VAD5.10±0.14,VA正常组5.78±0.26)(P<0.01),在肠道感染时降低更为显著(4.56±0.33)(P<0.01)。结论对肠粘膜局部细胞因子产生水平的调节可能是VAD影响粘膜免疫功能的重要机制。