The effects of feed restriction during in utero and postnatal development in rats.

This study determined the effects of feed restriction (FR) during in utero and postnatal life on standard reproductive toxicity and developmental immunotoxicity end points. Groups of 26 time-mated CD rats were fed various amounts of Purina 5002 diet from gestation day 7 through lactation. Control rats were fed once per day in amounts based on historical control feed consumption data, while the amounts fed to the FR groups were reduced by 10% (10% FR), 30% (30% FR), or 50% (50% FR) relative to controls. Selected F1 weanlings were necropsied on postnatal day (PND) 22, assessed for immunotoxicity end points between PND 22 and 27 or PND 52 and 56, or maintained on FR through PND 70. Thereafter, half the remaining F1 rats in each group were fed ad lib (recovery subgroup), while the rest continued on FR. Both subgroups were necropsied at 21 weeks of age. In the 10% FR group, slight decreases in maternal body weight had no effect on F1 offspring body weights, but did decrease F1 liver weights. FR at the 30% level reduced maternal body weights by 10-20%, reduced F1 offspring body weights by as much as 21%, caused changes in numerous weanling organ weights, but did not affect reproductive or immune system function. Dams in the 50% FR group were 17-32% lighter than controls, resulting in F1 body weights that were 12-47% lower than controls. F1 estrous cycle length was increased, puberty was delayed by 6 days (males and females), and anogenital distance, epididymal sperm counts, and all organ weights were decreased in this group. Antibody responses were unaffected despite decreased spleen and thymus weights. Essentially all effects of feed restriction showed evidence of reversibility.     

Dietary Mg and/or K restriction enhances paraquat toxicity in rats

Effect of mineral restriction was studied to clarify which mineral in the diet is most indispensable in preventing paraquat (PQ) toxicosis. ODS rats were chosen as the experimental animal owing to the inability to synthesize vitamin C similarly to humans. Rats were fed with either mineral-adequate or restricted diets dosed with 125 ppm PQ. The mineral-adequate diet was based on the American Institute of Nutrition-76, and the restricted diet was one-half the amounts. Measurements were made on the onset day of PQ toxicosis, body weight changes during the feeding experiment, and changes of two acute phase reactant proteins – cysteine proteinase inhibitor and α1-proteinase inhibitor. The minerals tested were divided into three classes: I, largely needed, Ca, K, Na, and Mg; II, moderately needed, Mn, Fe, Zn, and Cu; and III, minutely needed, Cr and Se, respectively. Rats fed with a Mg-restricted diet showed a severe toxicosis but those with a K-restricted diet, a mild toxicosis. No appreciable effect was observed by restriction of other minerals. A synergistic effect was observed in the restriction of Mg and K. Received: 16 September 1997 / Accepted: 25 February 1998     

Enhanced fecal elimination of stored hexachlorobenzene from rats and rhesus monkeys by hexadecane or mineral oil

The effect of various dietary treatments on the fecal excretion of [¹⁴C]-hexachlorobenzene (HCB) was studied in rats and rhesus monkeys. Cholestyramine and sesame oil failed to influence fecal excretion of HCB and/or metabolites. However, dietary administration of n-hexadecane (5%) increased fecal excretion of radioactivity 4–13-fold in rats and rhesus monkeys. Similarly, mineral oil in the diet (5%) of rhesus monkeys elicited a 6–9-fold increase in fecal excretion of HCB and/or metabolites. As a result of the mineral oil treatment, an enhanced depletion of HCB from blood and also of the stored HCB from adipose tissue was observed. The concentration of HCB in the blood declined in accordance with decreasing storage levels of HCB in adipose tissue. The major site of elimination of HCB and/or metabolites seemed to be the intestine; in particular, the cecum and the colon ascendens. Both hexadecane and mineral oil appeared to stimulate specifically this elimination pathway.     

Colestipol and energy restriction as an approach to hasten removal of PBBs from chickens

Male White Leghorn chickens were fed either 0.1 or 1.0 ppm fireMaster FF-1 (FF-1) for 21 d. During the withdrawal phase, the chickens were fed 0, 0.5, or 2.5% colestipol hydrochloride, and anion exchange resin. Also, calories were restricted to 80% of control intake within certain groups during the first 14 d in each of 2 consecutive 21-d withdrawal periods. In the caloric-restricted groups, colestipol was fed at 0, 0.625, or 3.125% to yield equal daily intake of colestipol to those fed 0, 0.5, or 2.5% concentrations. During the first 21 d of withdrawal, colestipol at 2.5-3.125%, but not 0.5-0.625%, hastened excretion of polybrominated biphenyls (PBBs) by 50%. During d 22-42 of withdrawal, a background level of PBBs contamination was detected, which tended to confound the results. Despite this, higher levels of colestipol lowered overall body burdens of PBBs by 80% in comparison to the overall level of residues in the other groups of chickens, and by 20% in comparison to their own levels 21 d earlier. Dietary colestipol resulted in chickens with lower carcass lipid content. The combination of energy restriction plus colestipol at 2.5-3.125%, which had the greatest impact in reducing body weight gain and carcass lipid, seemed to be the most favorable treatments for hastening excretion of PBB residues.     

Effect of chronic protein restriction on motor co-ordination and brain neurotransmitters in albino rats.

In this study we evaluated the motor co-ordination in Wistar strain albino rats that were maintained on a protein-restricted diet for a period of 1 year immediately after the weaning period, by substituting 75% of the normal diet with a carbohydrate-rich diet deficient in protein, for a period of 1 year immediately after the weaning period. This type of chronic protein restriction caused disturbances in motor co-ordination. It also caused a significant reduction in the basal levels of dopamine, norepinephrine, epinephrine and serotonin along with their metabolites homovanillic acid (HVA), vanillyl mandelic acid (VMA) and 5-hydroxy indoleacetic acid (5HIAA) and precursor L-dopa in the corpus striatum and cerebellum. Changes in these neurotransmitters could have caused altered co-ordination in the protein-restricted animals.     

左归丸联合橄榄油对大鼠去势后骨组织和骨密度的影响简

目的 观察左归丸联合橄榄油对去势后大鼠骨组织和骨密度的影响,为中医药治疗绝经后骨质疏松症提供实验依据.方法 对45只5～6月龄清洁型SD雌性大鼠进行随机等分成5组：①假手术组（Sham组）、②去卵巢组（OVX组）、③去卵巢＋左归丸组（ZGW组）、④去卵巢＋橄榄油组（Olive组）、⑤去卵巢＋左归丸＋橄榄油组（复方组）.对照组（①②）用药：均以生理盐水按1 ml/100 g体重,隔天1次灌胃.治疗组（③④⑤）用药：ZGW组：以中成药左归丸水溶液（每ml含0.2 g生药）按1 ml/100 g体重,隔天1次灌胃.Olive组：以初榨橄榄油按1 ml/100 g体重,隔天1次灌胃.复方组：以左归丸水溶液和初榨橄榄油交替每日灌胃1次.12周后分别左心室取血,检测血中血清雌二醇（E2）、白细胞介素-1（IL-1）、白细胞介素-6（IL-6）水平,放血处死后取出腰椎行双能X线骨密度测定,取左侧股骨近端1/3切片观察骨组织并计算骨小梁面积.结果 OVX组中血E2值明显低于Sham组（P〈0.01）;复方组中E2、IL-1、IL-6与Sham组无差异（P〉0.05）,复方组血E2值高于OVX组、ZGW组和Olive组（均P〈0.05）,IL-1值低于OVX组、ZGW组和Olive组（均P〈0.05）,复方组中IL-6值低于Olive组,差异有统计学意义（P〈0.05）,与ZGW组相比差异无统计学意义（P〉0.05）.光镜下观察发现OVX组中骨小梁稀薄、断裂,治疗组中骨小梁变密,连续性好,骨质疏松的病理骨组织现象改善,且三组间没有明显的区别.复方组骨密度较Olive组增加（P〈0.05）,但与ZGW组无显著差异性（P〉0.05）.复方组骨小梁面积较ZGW组增加（P〈0.05）,但与Olive组无显著差异性（P〉0.05）.结论 左归丸联合橄榄油能有效地减轻大鼠卵巢切除术引起的骨质丢失,且两者联合应用疗效或可能优于单用左归丸或橄榄油.     

海狗油保肝作用的实验研究

目的：观察海狗油对化学毒物所致小鼠、大鼠急性肝损伤及对长期喂食高脂饲料大鼠的影响。方法：实验分为6组(n=10)：即空白组、模型组、阳性药组、海狗油低、中、高剂量组。化学毒物乙硫氨酸或四氯化碳致急性肝损伤实验：小鼠和大鼠各组分别灌胃(ig)给供试药9d或7d；d7ig DL-乙硫氨酸，实验结束时测定肝脂；d6ip四氯化碳，实验结束时测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)和组织学检查。长期喂食高脂饲料大鼠实验：于实验d1一次性皮下注射小剂量四氯化碳并长期喂食高脂饲料造成脂肪肝模型大鼠，同时各组分别ig供试药，每天1次，连续10周后，称肝脏重量并计算肝脏系数，测定血脂、肝脂、脂质过氧化指标和组织学检查。结果：对乙硫氨酸致急性肝损伤的小鼠和大鼠ig给予海狗油(小鼠7．2 g·kg~(-1)，大鼠4．8g·kg~(-1))后，与模型组比较甘油三酯(TG)分别降低23％和16％(P＜0．01)；对四氯化碳致急性肝损伤的大鼠，海狗油4．8mg·kg~(-1)组使ALT降低24％(P＜0．01)、AST降低16％(P＜0．01)。长期喂食高脂饲料大鼠，与模型组比较，海狗油4．8mg·kg~(-1)组血清总胆固醇(TC)、游离脂肪酸(FFA)、肝重量及肝细胞内TG、TC、FFA和丙二醛(MDA)含量显著降低(P＜0．01)，超氧化物歧化酶(SOD)活性升高(P＜0．01)，组织学检查显示肝细胞内脂变程度减轻，脂滴减少。结论：海狗油对化学毒物所致急性肝损伤的肝细胞有保护作用，对脂肪肝的形成具有明显的预防作用。     

Effect of taurine on toxicity of oxidized fish oil in rats.

An attempt was made to study the effect of dietary taurine on the toxicity of oxidized fish oil in male Wistar rats. The rats were fed different diets with or without supplement of 5% taurine and 3% oxidized fish oil. After feeding diet with 3% oxidized fish oil and 5% taurine at the same time, taurine could improve the decrease of body weight and the glutathione (GSH) level in the liver, and the increase of relative ratios of liver and kidney weight to body weight and thiobarbituric acid-reactive substances (TBARS) level in the liver of rats caused by oxidized fish oil It also could reduce the activities of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) in the plasma of rats caused by oxidized fish oil. It was also found that taurine possessed a good recovering effect and a short-term preventing effect from the toxicity of oxidized fish oil in rats. Judging from these data, this indicates that taurine may play an important role in reducing the toxic effect of oxidized fish oil in rats.     

Oral meso-2,3-dimercaptosuccinic acid in pregnant Sprague-Dawley rats: teratogenicity and alterations in mineral metabolism. II. Effect on mineral metabolism

The effect of meso-2,3-dimercaptosuccinic acid (DMSA) on mineral metabolism was investigated in pregnant Sprague-Dawley rats. Animals were given by gavage doses of 0, 100, 300, or 1000 mg DMSA/kg/d on gestational d 6-15. On d 20 of gestation dams were killed and fetuses were removed from the uterus. The levels of calcium, magnesium, zinc, copper, and iron were measured in maternal liver, kidney, and intestine, as well as in whole fetus and in fetal liver. Mineral analysis of maternal and fetal tissues revealed pronounced effects of DMSA on mineral metabolism. The results of this investigation indicate a strong possibility that the negative effects of the drug on pregnancy are due in part to the changes in mineral metabolism.     

Effect of food restriction on hepatotoxicity of carbon tetrachloride in rats

Five-week-old Sprague-Dawley rats of both sexes were assigned to two types of feeding condition. One was fed ad libitum (AL) on commercial chow and another was fed a restricted amount of the chow (FR), approximately 75% of that fed in the AL condition. In each feeding condition, animals were orally administered carbon tetrachloride (CCl4) at levels of 0 (control), 0.1 or 0.2 ml/kg 6 days a week for 8 weeks. Lesions of the liver (hepatic cellular degeneration and fibrosis) and of the kidney (proximal tubular vacuolation and glomerular sclerosis) induced by CCl4 were aggravated in the FR group. The FR-control showed a higher metabolic activity of aniline in the liver than the AL-control group. Plasma lipid-peroxide (LPO) level was higher in the AL-control group than in the FR-control group. With CCl4 0.2 ml/kg treatment, however, the plasma LPO level was reversed between the AL and the FR groups. Taking together these somewhat unexpected results, it was concluded that (1) 25% food restriction increases toxicity of repeatedly administered CCl4 in rats, and (2) aggravation of CCl4 toxicity may be partly due to enhanced metabolic activation of CCl4 resulting from food restriction.     

Effect of mineral oil and/or cholestyramine in the diet on biliary and intestinal elimination of 2,4,5,2',4',5'-hexabromobiphenyl in the rhesus monkey

Addition of mineral oil to the diet (5%) of two rhesus monkeys that were dosed 29 wk earlier with 2,4,5,2',4',5'-hexabromobiphenyl (HBB) produced a 175% increase in fecal excretion of HBB. A third rhesus monkey was provided with a complete biliary bypass, which permitted the reintroduction of the monkey's own bile or the introduction of the same amount of exogenous bile, which was obtained from control donor monkeys. This experimental design made it possible to measure the portion of fecal excretion that was due to biliary elimination and the portion that was due to intestinal elimination. The effect of mineral oil and/or cholestyramine (CSA) on biliary and intestinal elimination of HBB in the rhesus monkey was then investigated. The results show that (1) fecal excretion of HBB and/or metabolites is due to both biliary and intestinal elimination; (2) during the first 2 wk after completion of dosing, mineral oil does not influence fecal excretion of HBB significantly; (3) 6-7 wk after completion of dosing, mineral oil enhances fecal excretion of HBB by 50%; (4) 8 wk after the last dose of HBB, 4% CSA in the diet increases fecal excretion of HBB and/or metabolites by about 50%; (5) mineral oil specifically stimulates intestinal elimination of HBB; and (6) combined administration of mineral oil and CSA results in an additive effect.     

Effect of olive and sunflower oil on serum lipids and myocardial triglyceride in rats.

Olive oil and sunflower oil (0.25 ml/100g/day) orally produced significant decrease in serum cholesterol and triglyceride levels in cholesterol-fed rats. Sunflower oil initially increased cholesterol and triglyceride levels and then decreased them to below normal values whereas olive oil decreased them throughout the experimental period of one month.     

Effect of menatetrenone (V.K2) on bone mineral density and bone strength in Ca/Mg deficient rats

Two experiments were carried out using 7-week-old male Wistar rats. Exp. 1: Rats in the intact group were fed with normal diet (0.5% Ca, 0.09% Mg). Ca/Mg deficient rats were fed low Ca (0.01%) diets containing 0.003, 0.015 or 0.09% Mg for 4 weeks. After 4 weeks, the bone mineral density (BMD) and maximum load in the femur were decreased in Ca/Mg deficient rats, but this was not dependent on dietary Mg concentration. The elasticity, stiffness, and Mg concentration in the femur of these rats were also decreased and Ca deposition in the kidney were increased, compared to those of normal rats, which were related to Mg concentration in the diet. From these results, Mg may play an important role in qualitative changes in bone (i.e., reduced stiffness). Exp. 2: We investigated the effects of V.K2 on the changes in BMD and bone strength in femur induced by low Ca/Mg (0.01%/0.003%) diet for 8 weeks. Compared to the intact group, Ca and Mg levels in serum and femur and cortical thickness, cortical area, and maximum load of the femoral midshaft were decreased in the Ca/Mg-deficient group. In these rats, PTH in the serum and renal Ca concentration were increased. In V.K2-treated rats, these changes in the serum Ca, Mg and PTH levels and the renal Ca concentration were improved. V.K2 also improved the decrease in maximum load in spite of no influence on the cortical thickness, cortical area and Mg concentration in the femur. These findings suggest that V.K2 may affect the qualitative change in bone.     

Elimination pattern and biodistribution of pcichlorferron in rats

Administration of [¹⁴C]chlorferron in a single oral dose of 0.5 and 20 mg/kg body weight to female rats resulted in a urinary excretion of > 74% of the given dose during the first 24 h. Approx. 8% of the dose was eliminated in faeces within 7 days. 7 days after dosing, very low levels of [¹⁴C]chlorferron-derived residues were detected in all analyzed organs. These findings indicated that chlorferron was absorbed from the gastro-intestinal tract in appreciable quantities, but was rapidly excreted mainly via the urine with small amounts only in the faeces.     

Dietary restriction and nicotine can reduce anxiety in female rats.

Anxiety may play a role in the initiation of smoking and there is evidence to suggest that sex and age may predetermine responses to nicotine. At present, the greatest increase in smoking is in women and it is often accompanied by dieting. The purpose of the present study was to investigate how the impact of dietary restriction might modify the effects of nicotine in female adult and adolescent rats. The effects of nicotine in the elevated plus-maze test of anxiety were compared in free-feeding animals and those subjected to dietary restriction that reduced body weight to 85% of free-feeding weight. In nondeprived adult females, nicotine (0.05-0.5 mg/kg, s.c.) reduced the percentage of time spent on the open arms, indicating anxiogenic effects. However, the effects of nicotine were dramatically changed in food-restricted adult females and 0.05 mg/kg had a striking anxiolytic effect. No significant effects of nicotine were found in the adolescent female rats, suggesting a role of circulating sex hormones in modulating nicotine's effects on anxiety. However, in the adolescent females, dietary restriction significantly increased the percentages of time spent and entries onto the open arms, without changing closed arm entries, indicating an anxiolytic effect. These results raise the important possibility that, in prepubertal girls, dietary restriction may have anxiolytic effects and this might contribute to the onset of anorexia. Circulating female hormones reduce this effect, but in adult females the combination of dietary restriction and nicotine may have important anxiolytic effects that impact on the initiation of regular smoking.     

Effects of feed restriction on the nucleolar structure and function in lymphocytes

Since malnutrition leads to adverse effects of several drugs on haemopoiesis and blood morphology, we tested if malnutrition itself could affect the nucleolar structure and function in rat lymphocytes. We report changes in the proportion of different nucleolar types that were dependent on the severity of feed restriction. The observed changes resemble those seen with cytostatics suggesting a possible link between feed restriction and haemotoxicity.     

Elimination of benfluron and its metabolites in the faeces and urine of rats.

The study of the biotransformation of the potential cytostatic benfluron has been continued. The elimination of benfluron and of nine of its metabolites whose structure had been established, mainly on the basis of the comparison of their IR, MS and NMR spectra with those of standards, was studied. After oral administration of 500 mg.kg-1 to rats, the amounts of these substances in the faeces and urine were followed up by high-performance liquid chromatography for five days. Striking qualitative and quantitative differences were observed in the elimination of benfluron and its metabolites by both routes.     

Effect of tamoxifen on bone mineral density and blood lipids in ovariectomized rats

Tamoxifen is widely used in breast cancer therapy and in the treatment of all stages of breast cancer including chemoprevention in women at high risk of the disease. The most important aspect of tamoxifen therapy concerns its influence on bone tissue and lipid metabolism. The aim of the study was to evaluate the effect of tamoxifen on bone metabolism and blood cholesterol levels in ovariectomized rats. The study was performed on Wistar rats treated with tamoxifen at 2 and 4 mg/kg/24 h. Total serum cholesterol and low density cholesterol were significantly increased in ovariectomized rats (3.24 mmol/l and 2.06 mmol/l) in comparison with sham operated control (2.68 mmol/l and 1.44 mmol/l) (p < 0.05). Total serum cholesterol and low density cholesterol in tamoxifen-treated rats were significantly decreased in comparision with the values in both sham-operated and ovariectomized control. Bone mineral content (BMC) and bone mineral density (BMD) of femurs of ovariectomized rats (0.32 g and 0.081 g/cm2) decreased significantly compared to sham-operated controls (0.42 g and 0.098 g/cm2) (p < 0.05). Tamoxifen prevented the bone mass reduction induced by ovariectomy. The treatment with tamoxifen at doses of 2 mg/kg/24 h and 4 mg/kg/24 h significantly increased BMC and BMD in comparison with ovariectomized control. The results suggest a beneficial influence of tamoxifen on bone tissue and lipid metabolism.     

辛伐他汀对骨质疏松大鼠血清骨钙素及骨密度的影响

目的:研究辛伐他汀对骨质疏松大鼠骨密度及血清骨钙素的影响,探讨其促进骨形成的作用。方法:36只雌性Wistar大鼠,随机分为4组。A组为假手术组,其余各组均行双侧卵巢切除术,术后1wk开始,A,B两组每只大鼠灌服生理盐水1.5mL·d-1,C组予辛伐他汀5mg·kg-1·d-1,D组予尼尔雌醇0.01mg·kg-1·d-1。10wk后处死大鼠,测量大鼠体重、股骨骨密度和血清骨钙素。结果:10wk后,B组大鼠体重高于A组,C,D组大鼠体重低于B组,均P<0.01。C,D组股骨骨密度(0.245±s0.007),(0.2430±0.0010)g·cm-2,高于B组(0.245±0.009)g·cm-2,血清骨钙素水平亦高于B组,均P<0.05,2组之间差异无显著意义(P>0.05)。结论:辛伐他汀能增加骨质疏松大鼠骨密度,提高骨钙素水平,促进新骨形成。