Food restriction in pregnant and lactating rats induces anemia and increases plasma lipid peroxidation in their progeny

This study was designed to investigate the effects of food restriction in female rats during pregnancy and lactation periods on hematologic parameters in their progeny. Twelve pregnant Wistar rats were randomly divided into 2 groups: a control (C) group with free access to a standard diet and a food-restricted group with alternating 24 hours of fasting and nonfasting from day 14 of pregnancy to day 14 of lactation. Food restriction reduced the number of red blood cells, hemoglobin concentration, and hematocrit values in mothers and their pups. In dams, plasma iron and folate levels were respectively reduced by 27% (P < .04) and 46% (P < .01) compared with the C group, whereas plasma copper and vitamin B₁₂ levels were unchanged. In pups, plasma iron, copper, and vitamin B₁₂ levels were decreased by 50%, 23%, and 16%, respectively, compared with those in the C group, whereas folate levels were unchanged. Blood glutathione levels were significantly decreased in mothers and pups compared with those in the C group. Erythrocyte osmotic fragility decreased, and plasma thiobarbituric acid–reactive substance (TBARS) levels increased only in pups. The results of the present study suggest that food restriction in rats provoked alterations in erythrocyte parameters in mothers, probably as a consequence of disturbance in the iron status. In pups, these changes might be pronounced by an increase in TBARS levels and erythrocyte osmotic fragility, which suggests involvement of lipid peroxidation, causing alteration of erythroid cells.     

2,4-Dichlorophenoxyacetic acid effects on nephrotoxicity in rats during late pregnancy and early postnatal periods

2,4-Dichlorophenoxyacetic acid (2,4-D) is largely used as a selective herbicide in Tunisia. The purpose of this study was to investigate the effects of 2,4-D on the kidneys of adult rats and their suckling pups. Female Wistar rats were divided into two groups: the controls and the treated rats that received 600 mg/L of 2,4-D in their drinking water from the 14th day of pregnancy until day 14 after delivery.Exposure to 2,4-D induced nephrotoxicity as evidenced by an increase in thiobarbituric acid reactive substances and protein carbonyl levels and a decrease in antioxidant enzyme activities such as catalase, superoxide dismutase, glutathione peroxidase in the kidneys of suckling pups and their mothers. In addition, a significant decline in kidney glutathione, non-protein thiol and vitamin C levels was also observed.Histological changes, seen in the kidney of mothers and their pups treated with 2,4-D are characterized by a narrowed Bowman’s space, tubular epithelial cells degeneration, widened tubular lumen and vascular congestion.     

Oxidative stress induced by gibberellic acid in bone of suckling rats

The present study investigates the bone maturity of suckling rats whose mothers were treated with gibberellic acid (GA₃). Female Wistar rats were divided into two groups: group I that served as controls and group II that received orally GA₃ (200 ppm) from the 14th day of pregnancy until day 14 after delivery. In the GA₃ group, an increase in body and femur weights as well as in femur length of pups was noted when compared to controls. Lipid peroxidation was demonstrated by high femur malondialdehyde levels, while superoxide dismutase, catalase, glutathione peroxidase activities, glutathione and vitamin C levels in femur decreased. GA₃ caused a decrease in calcium and phosphorus levels in bone. The calcium concentration in plasma increased and the phosphorus concentration decreased, while urinary levels of calcium decreased and those of phosphate increased. Moreover, plasma total tartrate-resistant acid phosphatase and total alkaline phosphatase increased. Bone disorders were confirmed by femur histological changes.     

Oxidative stress induced by chromium (VI) in bone of suckling rats

Exposure to hexavalent chromium Cr(VI) compounds is of concern in many Cr-related industries and their surrounding environments. K(2)Cr(2)O(7) is widely recognized as an animal and human carcinogen, mutagen, and teratogen. The present study investigated the bone maturity of suckling rats whose mothers were treated with K(2)Cr(2)O(7). Experiments were carried out on female Wistar rats given 700 ppm of K(2)Cr(2)O(7) in their drinking water from the 14th day of pregnancy until day 14 after delivery. Exposing dams to K(2)Cr(2)O(7) caused disorders in the bone of their progeny. As corollary to this, malondialdehyde levels increased, while glutathione, a non-protein thiol and vitamin C decreased. Alteration of the antioxidant system in the treated group was also confirmed by the significant decline of superoxide dismutase, catalase, and glutathione peroxidase activities. Furthermore, K(2)Cr(2)O(7) induced changes in bone mineralization, especially calcium and phosphorus levels, which decreased. Whereas, in plasma and urine, they increased and decreased inversely. These results suggest that K(2)Cr(2)O(7) accelerated bone resorption activity. In fact, in treated pups, total tartrate-resistant acid phosphatase, which reflected bone resorption, was enhanced while total alkaline phosphatase, which reflected bone formation, was reduced. The impairment of bone function was corresponded histologically.     

低剂量率裂变中子长期照射对大鼠外周血细胞的影响

目的 探讨低剂量率裂变中子长期照射对大鼠外周血细胞的影响。方法 96只雄性大鼠均分成对照组和照射组,照射组每天用低剂量率裂变中子(²⁵²Cf,吸收剂量率为0.35mGy/h)照射20.5h,在照射的第14d,28d,42d,56d,70d及停止照射后35d各取8只大鼠,用血细胞计数仪测定大鼠外周血WBC、RBC、PLT、HGB、MCV及HCT。结果 低剂量率中子累积照射可使大鼠外周血WBC明显下降,在累积剂量为0.3Gy和0.4Gy时白细胞数明显低于对照组(P<0.05),在累积剂量0.5Gy及停止照射后35d,照射组的WBC非常显著低于对照组(P<0.01);低剂量率中子照射在累积剂量为0.2Gy时,RBC反而显著高于对照组(P<0.01),同时红细胞压积(HCT)、血红蛋白(HGB)含量明显高于对照组,提示有血液浓缩现象。在其他剂量处,RBC则表现为下降趋势,但仅0.5Gy时RBC下降有统计差异(P<0.05);累积剂量为0.3Gy,0.4Gy及0.5Gy时,照射组HGB低于对照组(P<0.05);在停止照射后35d,照射组MCV明显高于对照组。仅发现在累积剂量为0.2Gy时,照射组PLT显著低于对照组(PLT)。结论 累积剂量0~0.5Gy的低剂量率裂变中子照射对大鼠外周血RBC及PLT的影响相对较少,但可造成大鼠外周血WBC减少,且在停止照射后一段时间,白细胞总数仍难以恢复至正常水平。     

Schisandra Chinensis Baillon regulates the gene expression of phase II antioxidant/detoxifying enzymes in hepatic damage induced rats

BACKGROUND/OBJECTIVES

This study investigated the antioxidant activities and hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats.

MATERIALS/METHODS

Sprague-Dawley (SD) rats were pretreated with SCE (300, 600, and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each animal, except those belonging to the normal control group, were injected with t-BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP injection.

RESULTS

Although no significant differences in AST and ALT levels were observed among the TC and SCE groups, the high-dose SCE group showed a decreasing tendency compared to the TC group. However, erythrocyte SOD activity showed a significant increase in the low-dose SCE group compared with the TC group. On the other hand, no significant differences in hepatic total glutathione (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) activities were observed among the TC and SCE groups. Hepatic histopathological evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced incidence of lesions, such as neutrophil infiltration, swelling of liver cells, and necrosis. In particular, treatment with a high dose of SCE resulted in induction of phase II antioxidant/detoxifying enzyme expression, such as glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit (GCLC).

CONCLUSIONS

Based on these results, we conclude that SCE exerts protective effects against t-BHP induced oxidative hepatic damage through the reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In addition, SCE regulates the gene expression of phase II antioxidant/detoxifying enzymes independent of hepatic antioxidant enzyme activity.     

锰对大鼠硒代谢的影响

鉴于贫硒与克山病发病有密切关系以及一些病区的人群既贫硒又富锰,本文研究了锰对大鼠硒代谢的影响。经腹腔给大鼠注射40mg/kg氯化锰5周,致血清和心肌锰含量明显增高,而血清和心肌硒含量以及全血和心肌谷胱甘肽过氧化物酶活性却显著降低。组织锰含量与硒含量和谷胱甘肽过氧化物酶活性呈负相关。在给予氯化锰的第7天,经胃管给予~(75)硒,锰组大鼠在服~(75)硒之后7天中总排硒量显著高于对照组大鼠,主要是由于锰促进慢相尿硒排泄所致。结果表明,锰对硒代谢有明显影响,即通过增加硒排泄量而致血、心肌硒含量和含硒酶活性显著降低。     

The effect of cholesterol feeding on lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in the liver of rats

Liver cholesterol, phospholipid, triglyceride, lipid peroxide and glutathione levels as well as glutathione peroxidase and glutathione transferase activities were determined in rats fed a high-cholesterol (2%, w/w), high-cholic acid (0.5%, w/w) diet for 3 months. Cholesterol feeding caused an increase in hepatic cholesterol and triglyceride levels, but no change was observed in hepatic phospholipid levels. In addition, a significant increase in hepatic lipid peroxide levels and a significant decrease in glutathione peroxidase and glutathione transferase activities have been observed. However, hepatic glutathione content after cholesterol feeding remained unchanged. These results show that cholesterol feeding leads to the stimulation of hepatic lipid peroxidation as well as impairment of glutathione-related enzyme activities in rats.     

Protective effect of alpha-lipoic acid in experimental spermatic cord torsion

OBJECTIVE: We investigated the effect of alpha-lipoic acid (LA) in rats that were subjected to torsion/detorsion of the spermatic cord in a comparative controlled experiment. METHODS: Forty-eight male Wistar rats, randomized in two groups, received intraperitoneal injections of LA (LA group; aqueous solution at 36 mg/kg of body weight per day) or equal volume of saline (control group) 21, 9, and 1 h before torsion of the spermatic cord. Rats in each group were distributed in four subgroups, each comprising six animals. All surgical procedures were performed under inhaled ether anesthesia. Ischemia was induced by 720-degree torsion of the spermatic cord for 3 h. The right testis was assessed through longitudinal scrotal incision. After each surgical procedure, scrotal incisions were closed with 4-0 nylon monofilament. Ipsilateral testes and arterial blood samples were collected at the end of ischemia and 1, 3, and 6 h after detorsion. Thiobarbituric acid-reactive substances and reduced glutathione levels (micromoles per gram of wet tissue) were assayed in testis. Total antioxidant power was measured in blood plasma. RESULTS: LA pretreatment promoted a significant decrease in testicular concentrations of thiobarbituric acid-reactive substances and simultaneously induced an increase in reduced glutathione concentrations at all time points studied. Plasma total antioxidant power levels increased significantly during reperfusion (T-1) in LA-treated rats compared with control rats. CONCLUSION: LA administered before torsion of the spermatic cord showed significant protective effects against ischemia/reperfusion injury by decreasing lipid peroxidation and regulating testicular reduced glutathione and plasma total antioxidant power levels.     

Relationship Between Blood Lead Levels and Hematological Indices in Pregnant Women

Several studies have revealed a negative association between blood lead levels and hematological impairment. In this cross-sectional study, we examined the relationship between blood lead levels and hematological indices in 292 pregnant women from Durango, Mexico. Apparently healthy pregnant women, aged 14–41 years and at 3–41 weeks of gestation, were recruited between June 2007 and May 2008. Blood lead and hematological indices were measured. The mean blood lead was 2.79 ± 2.16 μg/dL, and lead levels ≥5 μg/dL were detected in 25 women (8.6%). Hemoglobin, hematocrit, and red blood cells count were significantly higher in pregnant women with a blood lead concentration of ≥5 μg/dL than the group with lower blood lead levels (p < .05). Mean corpuscular volume and mean corpuscular hemoglobin were not significantly related to lead levels. Hemoglobin and hematocrit showed a non-significant positive correlation with blood lead, but the correlation between red blood cell count and blood lead levels was statistically significant (r = 0.185, p = .002). The findings suggest that a positive association between blood lead and some hematological indices may occur at relatively low blood lead concentration (mean < 5 μg/dL).     

Longitudinal selenium status in healthy British adults: assessment using biochemical and molecular biomarkers

Human selenium (Se) requirements are currently based on biochemical markers of Se status. In rats, tissue glutathione peroxidase-1 (Gpx1) mRNA levels can be used effectively to determine Se requirements; blood Gpx1 mRNA levels decrease in Se-deficient rats, so molecular biology-based markers have potential for human nutrition assessment. To study the efficacy of molecular biology markers for assessing Se status in humans, we conducted a longitudinal study on 39 subjects (age 45 +/- 11) in Reading, UK. Diet diaries (5 day) and blood were obtained from each subject at 2, 8, 17 and 23 weeks, and plasma Se, glutathione peroxidase (Gpx3) enzyme activity, and selenoprotein mRNA levels were determined. There were no significant longitudinal effects on Se biomarkers. Se intake averaged 48 +/- 14 microg/d. Plasma Se concentrations averaged 1.13 +/- 0.16 micromol/l. Plasma Se v. energy-corrected Se intake (ng Se/kJ/d) was significantly correlated, but neither Gpx3 activity v. Se intake (ng Se/kJ/d) nor Gpx3 activity v. plasma Se was significantly correlated. Collectively, this indicates that subjects were on the plateaus of the response curves. Selenoprotein mRNAs were quantitated in total RNA isolated from whole blood, but mRNA levels for Gpx1, selenoprotein H, and selenoprotein W (all highly regulated by Se in rodents), as well selenoprotein P, Gpx3, and phospholipid hydroperoxide glutathione peroxidase were also not significantly correlated with plasma Se. Thus selenoprotein molecular biomarkers, as well as traditional biochemical markers, are unable to further distinguish differences in Se status in these Se replete subjects. The efficacy of molecular biomarkers to detect Se deficiency needs to be tested in Se-deficient populations.     

Blood mercury concentrations following methyl mercury exposure in adult and infant monkeys

Female monkeys (Macaca fascicularis) were dosed chronically with the equivalent of 10, 25, or 50 micrograms/kg/day methyl mercury until at least 90% of estimated blood equilibrium was reached and were then bred to untreated males. Infants were dosed with the same dose their mothers had received. An additional group of infants was dosed with 50 micrograms/kg/day beginning at birth. Infants exposed in utero were born with higher (1.7x) mercury levels than their mothers, but blood mercury levels of the offspring decreased to less than one-half that of the mothers. The steady-state blood levels of the group exposed postnatally were not different from steady-state levels of the group exposed in utero plus postnatally. When dosing was discontinued, the rate coefficient of elimination from blood did not differ between the adults (mothers) and the in utero plus postnatally exposed group, while that of the group exposed postnatally only was lower. There was no indication of a relationship in the rate of elimination for mother-infant pairs. These results suggest that the kinetics of methyl mercury in blood are complicated and may depend on the age of the individual when exposure begins.     

吉林人参亚慢性毒性试验中大鼠血液学变化的研究

目的观察吉林人参在亚慢性毒性试验中对Wistar大鼠血液学变化的影响。方法选取Wistar大鼠160只进行亚慢性毒性试验,随机分为对照组和实验组。实验组分为8.0g/(kg.d)、6.5g/(kg.d)、5.0g/(kg.d)3个剂量组,给予含有不同剂量吉林人参样品的饲料喂饲大鼠90d,在实验中期和末期采用荧光染色法,分别检测大鼠血红蛋白(Hb)、红细胞(RBC)数、白细胞(WBC)数及白细胞分类中淋巴细胞、单核细胞、嗜中性细胞、嗜酸性细胞、嗜碱性细胞百分比等血液学指标。结果各剂量组末期红细胞和白细胞含量较中期明显增加(P<0.05),各剂量组大鼠血液学指标与对照组比较,差异无统计学意义(P>0.05)。结论在亚慢性毒性试验中,食用吉林人参未对大鼠血液学指标产生明显影响。     

Vanadium Decreases Hepcidin mRNA Gene Expression in STZ-Induced Diabetic Rats,Improving the Anemic State

Diabetes is a disease with an inflammatory component that courses with an anemic state. Vanadium (V) is an antidiabetic agent that acts by stimulating insulin signaling. Hepcidin blocks the intestinal absorption of iron and the release of iron from its deposits. We aim to investigate the effect of V on hepcidin mRNA expression and its consequences on the hematological parameters in streptozotocin-induced diabetic Wistar rats. Control healthy rats, diabetic rats, and diabetic rats treated with 1 mgV/day were examined for five weeks. The mineral levels were measured in diet and serum samples. Hepcidin expression was quantified in liver samples. Inflammatory and hematological parameters were determined in serum or whole blood samples. The inflammatory status was higher in diabetic than in control rats, whereas the hematological parameters were lower in the diabetic rats than in the control rats. Hepcidin mRNA expression was significantly lower in the V-treated diabetic rats than in control and untreated diabetic rats. The inflammatory status remained at a similar level as the untreated diabetic group. However, the hematological profile improved after the V-treatment, reaching similar levels to those found in the control group. Serum iron level was higher in V-treated than in untreated diabetic rats. We conclude that V reduces gene expression of hepcidin in diabetic rats, improving the anemic state caused by diabetes.     

实验性矽肺模型大鼠外周血CD4＋CD25＋Foxp3＋调节性T细胞的变化及意义

[目的]研究实验性矽肺大鼠在染尘后病情发展不同阶段外周血CD4＋CD25＋T细胞和CD4＋CD25＋Foxp3＋调节性T细胞（Treg细胞）的频率,初步探讨Treg细胞在矽肺发生发展中的可能作用。[方法]将40只健康雄性SD大鼠随机分为模型组和对照组,模型组24只,对照组16只。模型组以非暴露方式气管内一次性注入1mL石英粉尘悬液（40mg／mL）建立大鼠矽肺模型,对照组大鼠气管内一次性注入等容量的灭菌生理盐水。染尘后第7、14、21及28天分别处死6只模型组和4只对照组大鼠,用流式细胞术检测大鼠外周血CD4＋CD25＋细胞及Treg细胞的百分率。[结果]第7天,急性肺泡炎期间,模型组CD4＋CD25＋T细胞和Treg细胞较正常对照组频率明显降低（P〈0．05）;第14天,矽性肉芽肿形成期,模型组CD4＋CD25＋细胞和Treg细胞数量回升,接近正常水平;第21天,矽性肉芽肿增多期间,模型组CD4＋CD25＋T细胞和Treg细胞频率较正常对照组略高,但差异不具有统计学意义;第28天矽性肉芽肿增多并大量纤维化期间,模型组CD4＋CD25＋T细胞和Treg细胞频率明显增加,与对照组相比差异具有统计学意义（P〈0．05）。[结论]Treg细胞可能在维持免疫耐受和矽肺的发生发展中发挥重要作用。     

Whey protein, as exclusively nitrogen source, controls food intake and promotes glutathione antioxidant protection in Sprague-Dawley rats

The inclusion of whey protein concentrates (WPC) in the diet can lead to a decrease in food intake. Considering that excessive food intake and weight gain are correlated with increased oxidative stress and other risk factors, the anorectic action of WPC may have important clinical implications. The aims of the current study were to verify the effects of WPC in comparison with those of casein on food intake, weight, and oxidized glutathione (GSSG) and total glutathione (GSH) concentrations in the blood and liver with or without oxidative stress induced by oral carbon tetrachloride intoxication. Male Sprague-Dawley rats were fed a balanced liquid diet for 3 weeks. Half of the rats received WPC (group P), while the control group received casein (group C). Group P rats ate significantly less than group C rats (p < 0.0001), and their weights decreased significantly. After carbon tetrachloride intoxication, there was a significant increase in GSH in rats of group P compared with the levels in rats of group C both in the liver (GSH group P 4,994 ± 652.6, group C 2,196 ± 323.2 nmol/mg, p < 0.01) and in the blood (GSH group P 1,368 ± 69.56, group C 1,088 ± 48.35 nmol/ml, p < 0.05). These findings indicate that WPC is effective in reducing food intake and preventing weight gain, and it may also play a protective role against oxidative stress by increasing glutathione synthesis in the liver.     

Selenium repletion and glutathione peroxidase--differential effects on plasma and red blood cell enzyme activity

We studied three children with chronic gastrointestinal disease who had been on intravenous hyperalimentation for periods of time ranging from 4 to 23 months. Each child was found to have low plasma and red blood cell glutathione peroxidase activity. This was associated, in the two children tested, with a marked deficiency of serum selenium. Their plasma glutathione peroxidase levels ranged between 4 and 24% of normal and their red blood cell levels ranged between 4 and 14% of normal. The intravenous alimentation was then supplemented with sodium selenite (240 micrograms Se/d). Within 4-5 weeks, the plasma glutathione peroxidase activity returned to normal. Red cell glutathione peroxidase activity remained essentially unchanged for 4-6 weeks, after which it increased over the following 3-4 months. Red cells were separated by density on a continuous Percoll-diatrizoate gradient. In normal individuals, the specific activity of glutathione peroxidase did not differ across the gradient despite a 2.5-fold difference in the specific activity of pyruvate kinase. When studied initially, glutathione peroxidase activity from the deficient patients did not change across the gradient. As the red cell enzyme activity increased with selenium repletion, the highest specific activity was initially found at the top of the gradient (youngest cells). After 3-4 months of supplementation, the specific activity became equal across the gradient. Thus, with selenium repletion, there is a rapid increase in plasma glutathione peroxidase activity, a 4-6 week lag prior to an increase in red cell enzyme activity, and the increase in red cell activity is due to newly synthesized red cells made in the presence of selenium.     

Effects of short- and long-term exposure to ozone on heart rate and blood pressure of emphysematous rats

Electrocardiogram and arterial blood pressure of elastase-treated emphysematous rats (E rats) and saline-treated control rats (S rats) were recorded continuously during exposure to either 1 ppm ozone (O3) for 3 hr or 0.5 ppm O3 for 6 hr. The heart rates (HRs) of both groups decreased to about 50 and 65% of the initial levels at the end of 1 ppm and 0.5 ppm O3 exposure, respectively. Mean arterial blood pressures (MAPs) also decreased to about 76 and 82%, respectively. There was no significant difference in these responses between E and S rats, although the levels of HRs and MAPs of the E rats were always a little lower than those of the S rats. Another group of E and S rats was continuously exposed to 0.2 ppm O3 for 4 weeks. The HRs of both E and S groups decreased to about 81 and 88% of the initial levels on the first day, respectively, although they recovered completely by the third day. No significant difference in the variation of HRs during exposure was noted between E and S rats. However, the HR responses of these rats to a challenge exposure of 0.8 ppm O3 for 1.5 hr appeared to be different. That is, S rats were more tolerant of the challenge exposure to O3 for 1.5 hr than the E rats.     

硝酸羟胺亚慢性染毒对大鼠血液系统的影响

目的在硝酸羟胺(HAN)亚慢性染毒大鼠的基础上,初步探讨大鼠染毒后对血液系统的影响。方法Wistar大鼠160只随机分为4组:分别为HAN6.97、13.93和27.86mg/kg组和生理盐水阴性对照组,HAN组与对照组大鼠均以隔日腹腔注射的方式染毒,连续染毒13周后处死3/4(每组30只)动物,剩余1/4(每组10只)动物停止染毒再饲养4周后处死,分别检测染毒期与恢复期相关血液指标,网织红细胞计数及骨髓细胞各系增生情况。结果染毒期,HAN染毒组大鼠白细胞数显著升高,红细胞数和血红蛋白显著降低(P<0.05);染毒组大鼠网织红细胞计数明显高于对照组(P<0.01),与染毒剂量显著正相关;骨髓细胞中红细胞系增生明显,以中幼红和晚幼红细胞增多为主,粒/红比例明显下降,各染毒组与对照组比较差异有统计学意义(P<0.05)。恢复期,血常规、网织红细胞计数及骨髓细胞各系增生情况与对照组比较均无统计学意义。结论HAN长期染毒对大鼠骨髓造血系统有一定的损伤,主要表现为对红细胞系的毒作用。