Vitamin C ameliorates fluoride-induced embryotoxicity in pregnant rats

Oral administration of sodium fluoride (40 mg/kg body weight) from day 6 to 19 of gestation caused, as compared to control, significant reductions in body weight, feed consumption, absolute uterine weight and number of implantations. Significantly higher incidence of skeletal (wavy ribs, 14th rib, <6 sternal centre, dumbell-shaped second and fifth sternebrae, incomplete ossification of skull and thickening of tibia) and visceral (subcutaneous haemorrhage) abnormalities were also observed in NaF-treated dams than that of control. Oral administration of vitamin C (50 mg/kg body weight) and vitamin E (2 mg/0.2 ml olive oil/animal/day) from day 6 to 19 of gestation along with NaF significantly ameliorates NaF-induced reductions in body weight, feed consumption, absolute uterine weight (only with vitamin E treatment) and number of implantations. As compared with NaF-treated alone, the total percentage of skeletal and visceral abnormalities were significantly lowered in fluoride plus vitamin C-treated animals. Vitamin E was less effective. These findings suggest that vitamin C significantly reduced the severity and incidence of fluoride-induced embryotoxicity in rats.     

Comparative distribution and embryotoxicity of acetylsalicylic acid in pregnant rats and rhesus monkeys.

Acetylsalicylic acid was given orally to pregnant rats on gestation Days 9–12 and to pregnant monkeys on Days 23–32 and to nonpregnant females of both species at doses of 100 and 150 mg/kg twice daily. Concentrations of salicylic acid were determined in maternal plasma, embryo, decidua, placenta, and chorionic and amniotic fluids at 1, 2, 4, 8, and 17 hr after the last dosage. Total salicylic acid concentrations in plasma after comparable doses were generally higher in rats than in monkeys and in nonpregnant than in pregnant rats, but concentrations varied in pregnant vs nonpregnant monkeys. Unbound salicylate in rat plasma ranged between 30 and 50% of the total plasma concentration and was closely paralleled by the concentration in the rat embryo. Unbound salicylate in monkey plasma was lower, ranging between 17 and 30% of the total plasma concentration and was to some degree paralleled by the concentration in the monkey embryo. The greater embryotoxicity of acetylsalicylic acid in the rat than in the monkey was correlated with higher concentrations and longer duration of concentrations in the respective embryos on a day-to-day basis.     

Neuroprotective activity of Matricaria recutita against fluoride-induced stress in rats

Context:?Oxidative stress plays a key role in pathophysiology of many neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and so on. Although Matricaria recutita L. (Asteraceae), German chamomile, is traditionally used for central nervous system (CNS)-related diseases, its antistress properties have received little attention.

Objective:?The present study evaluated the neuroprotective effect of German chamomile against aluminium fluoride (AlF₄^?)-induced oxidative stress in rats.

Materials and methods:?The Sprague-Dawley rats of either sex (200–250?g) were selected and grouped as: group I received normal saline; group II received AlF₄^? (negative control); groups III, IV, and V received 100, 200, and 300?mg/kg, orally, German chamomile methanol extract (GCME) along with AlF₄^?; and group VI received quercetin (25?mg/kg, i.p.) + AlF₄^?, respectively. After 10 days treatment with GCME, oxidative stress was induced by administering AlF₄^? through drinking water for 7 days. Then, the protective antioxidant enzyme levels were measured and the histopathological studies were carried out.

Results:?The GCME showed dose-dependent neuroprotective activity by significant decrease in lipid peroxidation (LPO) and increase in the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and total thiol levels in extract-treated animals as compared with negative control group (P?<?0.001). The histopathological studies also revealed the potent neuroprotective action of German chamomile against oxidative brain damage.

Conclusion:?The present study for the first time shows potent neuroprotective activity of the methanol extract of German chamomile against AlF₄^?-induced oxidative stress in rats.     

Teratogenicity and embryotoxicity study of Green S in rats

Daily oral doses of 0 (control), 250, 500 or 1000 mg Green S/kg body weight were given to groups of 30 pregnant rats on days 0–19 of pregnancy. This treatment did not adversely influence maternal body weight, the numbers of implanations, of pre- or post-implantation losses or of live foetuses, the sex ratio or the weight of the litters or foetuses. No definite abnormalities were seen and the only finding in the examination of stained skeletons was a slightly more advanced ossification of the forelimbs of the offspring from females given 500 or 1000 mg Green S/kg/day. More foetuses with mucus in the trachea were found in the treated groups than in the controls but this was not considered to be a teratogenic effect. Thus no embryotoxic or teratogenic effects were detected with doses of up to 1000 mg Green S/kg/day throughout pregnancy.     

Vitamin E ameliorates aflatoxin-induced alterations in the epididymis of mice

The present investigation was an attempt to evaluate the effect of aflatoxin on biochemical and histopathological changes in the epididymis of mice and its possible amelioration on pre-treatment with vitamin E. Adult male albino mice were orally administered with 25 and 50 mg of aflatoxin/animal/day (750 and 1500 mg/kg body weight) for 45 days. Epididymis was isolated and processed for biochemical analysis. As compared with the control, absolute and relative epididymal weights were significantly reduced in aflatoxin-treated mice. Aflatoxin treatment caused significant, dose-dependent reduction in protein and sialic acid contents in caput and cauda epididymis than that of vehicle control. While activities of succinic dehydrogenase and adenosine triphosphatase were significantly reduced, acid phosphatase activity was significantly higher in caput and cauda epididymis of aflatoxin-treated mice than that of vehicle control. Pyknosis of epithelial cell nuclei, disorganization of epithelium, clumping of stereocilia and lumen devoid of sperms in caput and cauda epididymis were observed. Thus, pre-treatment with vitamin E (2 mg/0.2 mL olive oil/ animal/day) significantly ameliorated aflatoxin-induced changes, measured by biochemical and histopathological parameters.     

Chronic contamination with 137Cesium affects Vitamin D3 metabolism in rats

Twenty years after Chernobyl disaster, many people are still chronically exposed to low dose of (137)Cs, mainly through the food consumption. A large variety of diseases have been described in highly exposed people with (137)Cs, which include bone disorders. The aim of this work was to investigate the biological effects of a chronic exposure to (137)Cs on Vitamin D(3) metabolism, a hormone essential in bone homeostasis. Rats were exposed to (137)Cs in their drinking water for 3 months at a dose of 6500 Bq/l (approximately 150 Bq/rat/day), a similar concentration ingested by the population living in contaminated territories in the former USSR countries. Cytochromes P450 enzymes involved in Vitamin D(3) metabolism, related nuclear receptors and Vitamin D(3) target genes were assessed by real time PCR in liver, kidney and brain. Vitamin D, PTH, calcium and phosphate levels were measured in plasma. An increase in the expression level of cyp2r1 (40%, p<0.05) was observed in the liver of (137)Cs-exposed rats. However a significant decrease of Vitamin D (1,25(OH)D(3)) plasma level (53%, p=0.02) was observed. In brain, cyp2r1 mRNA level was decreased by 20% (p<0.05), while the expression level of cyp27b1 is increased (35%, p<0.05) after (137)Cs contamination. In conclusion, this study showed for the first time that chronic exposure with post-accidental doses of (137)Cs affects Vitamin D(3) active form level and induces molecular modifications of CYPs enzymes involved its metabolism in liver and brain, without leading to mineral homeostasis disorders.     

维生素AD制剂中维生素D的净化分离

目的:对维生素AD制剂中的维生素D进行净化分离,实现其含量测定。方法:采用Turbo VapⅡ型全自动氮吹仪及Waters 1515/2489/2707自动馏分收集装置对维生素AD制剂中维生素D进行净化分离,照《中国药典》2010年版二部附录规定方法进行含量测定。结果:氮吹仪水浴温度设为50℃,压力25 psi时,回收率良好,为98%;净化分离系统在1.25~12.5μg范围内分离效果良好,RSD=0.4%,回收率为96%。结论:采用Turbo VapⅡ型全自动氮吹仪及Waters 1515/2489/2707自动馏分收集装置对维生素AD制剂中维生素D可以进行有效净化分离,进而通过正相色谱完成其含量测定,方法适用范围较宽,重复性、回收率良好,操作简便。     

Suppression of uric acid and lactate production by sodium acetate ameliorates hepatic triglyceride accumulation in fructose-insulin resistant pregnant rats

High fructose intake has been associated with perturbed lipid, uric acid and lactate homeostasis. However, consumption of fructose-sweetened beverages is not usually regulated during pregnancy. The effect of short-chain fatty acid (acetate) on the metabolic effects of high fructose intake during pregnancy is not known. We hypothesized that acetate prevents gestational fructose-induced hepatic triglyceride (TG) accumulation by suppressing uric acid and lactate production. Pregnant Wistar rats were randomly separated into three groups (n = 6/group) receiving drinking water (CON), 10 % (w/v) fructose drink (FRU) and 10 % (w/v) fructose with 200 mg/kg (w/w; p.o.) sodium acetate (FRU + ACE) daily for nineteen days. Fructose intake resulted in increased body weight gain, liver weight, fluid intake, visceral fat, insulin resistance, fasting blood glucose, insulin, plasma and hepatic TG, total cholesterol, free fatty acid, lipid peroxidation, adenosine deaminase, xanthine oxidase, uric acid, lactate, lactate dehydrogenase, and liver injury marker enzymes. However, gestational high fructose intake led to depressed plasma and hepatic glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant barrier, adenosine and food intake. All these effects except water intake and food intake were abated by sodium acetate. These results demonstrate that maternal fructose-enriched drink would cause hepatic TG accumulation that is associated with perturbed glucose, uric acid, lactate homeostasis, and G6PD-dependent antioxidant barrier. These results also demonstrate that acetate protects the liver against gestational fructose-induced TG accumulation by inhibiting uric acid and lactate production. Thus, acetate may be useful in the treatment of hyperuricemia- and hyperlactatemia-related disorders.     

Lack of oral embryotoxicity/teratogenicity with D-ribose in Wistar rats.

The present oral embryotoxicity/teratogenicity study of d-Ribose (DR) was conducted in female rats; 28 rats/group were exposed via the diet to 0, 5, 10, or 20% DR (0.0, 4.25, 7.94, 9.91g/kg body weight/day), from day 0 of gestation until Caesarian section and maternal sacrifice on day 21. All animals survived to the end of the study. Fecundity index, gestation index, pre-implantation loss, post-implantation loss, and sex ratio were all unaffected by treatment with DR. External observations of fetuses and placentas were unremarkable across the study groups. Mean fetal and placental weights, across all viable fetuses, did not differ significantly between treated and control groups. Observations of visceral malformations, anomalies, and variations were unremarkable and did not differ between treated and control groups. In summary, administration of DR to pregnant rats at concentrations up to 20% of the diet resulted in no significant adverse effects on the developing embryo/fetus at doses that were not otherwise a severe metabolic stress on the dam. A No Observed Adverse Effect Level (NOAEL) for teratogenicity could be seen at a concentration of 5% DR in the diet, corresponding to an average daily intake of DR of between 3.64 and 4.61g/kg body weight/day.     

Quetiapine ameliorates stress-induced cognitive inflexibility in rats

The antidepressant action of quetiapine has been demonstrated in clinical and preclinical studies. Nevertheless, little is known about its effectiveness in the treatment of frontal-like cognitive disturbances that may be associated with stress-related disorder. Therefore, the aim of the present study was to investigate whether quetiapine would prevent and/or reverse stress-induced cognitive impairments in a rat model of prefrontal cortex (PFC)-dependent attentional set-shifting task (ASST). Because quetiapine augmentation to selective serotonin reuptake inhibitors (SSRIs) has recently been proven to be beneficial in neuropsychiatric disorders, a separate experiment was designed to assess the impact of combined administration of inactive doses of quetiapine and escitalopram on ASST performance in rats. According to our previous studies, 1?h daily exposure to restraint stress for 7 days significantly and specifically impaired extra-dimensional (ED) set-shifting ability of rats. Quetiapine (2.5?mg/kg, PO) given to rats prior to the restraint sessions completely prevented this stress-induced cognitive inflexibility. Similar effect was demonstrated after pretreatment with the α1-adrenoceptor antagonist, prazosin (1?mg/kg, IP). Moreover, acute administration of quetiapine before the test reversed set-shifting deficits in stressed rats (0.63, 1.25 and 2.5?mg/kg, PO) and improved ED performance of cognitively unimpaired control animals (1.25 and 2.5?mg/kg, PO). Finally, the combined administration of inactive doses of quetiapine (0.63 and 0.3?mg/kg in control and stressed rats, respectively) and escitalopram (0.3?mg/kg, IP) facilitated set-shifting performance in either control or stressed rats. In conclusion, quetiapine administration either prevented or reversed stress-induced cognitive inflexibility in rats. In addition to promoting of set-shifting by itself, quetiapine also enhanced the procognitive efficacy of escitalopram. The potential contribution of the antagonism at α1-adrenoceptors to the mechanisms underlying the protective action of quetiapine requires further evaluation. These findings may have therapeutic implications for the treatment of frontal-like disturbances, particularly cognitive inflexibility, in stress-related psychiatric disorders. This article is part of a Special Issue entitled 'Cognitive Enhancers'.     

Vitamin D in cancer chemoprevention

Abstract

Context: There is increasing evidence that Vitamin D (Vit D) and its metabolites, besides their well-known calcium-related functions, may also exert antiproliferative, pro-differentiating, and immune modulatory effects on tumor cells in vitro and may also delay tumor growth in vivo.

Objective: The aim of this review is to provide fresh insight into the most recent advances on the role of Vit D and its analogues as chemopreventive drugs in cancer therapy.

Methods: A systematic review of experimental and clinical studies on Vit D and cancer was undertaken by using the major electronic health database including ISI Web of Science, Medline, PubMed, Scopus and Google Scholar.

Results and conclusion: Experimental and clinical observations suggest that Vit D and its analogues may be effective in preventing the malignant transformation and/or the progression of various types of human tumors including breast cancer, prostate cancer, colorectal cancer, and some hematological malignances. These findings suggest the possibility of the clinical use of these molecules as novel potential chemopreventive and anticancer agents.     

Yin-Chen-Hao-Tang ameliorates obstruction-induced hepatic apoptosis in rats

The accumulation of hydrophobic bile acids in the liver is considered to play a pivotal role in the induction of apoptosis of hepatocytes during cholestasis. Thus, factors that affect apoptosis may be used to modulate liver fibrosis. Yin-Chen-Hao-Tang (YCHT) decoctions have been recognised as a hepatoprotective agent for jaundice and various types of liver diseases. We used an experimental rat model of bile-duct ligation (BDL) to test whether YCHT plays a regulatory role in the pathogenesis of hepatic apoptosis. BDL-plus-YCHT groups received 250 or 500 mg kg (-1) YCHT by gavage once daily for 27 days. YCHT significantly ameliorated the portal hypertensive state and serum TNF-alpha compared with the vehicle-treated control group. In BDL-plus-YCHT-treated rats, hepatic glutathione contents were significantly higher than than in BDL-only rats. BDL caused a prominent liver apoptosis that was supported by an increase in Bax and cytochrome c protein and increased expression of Bax and Bcl-2 messenger RNA. The normalising effect of YCHT on expression of Bax and Bcl-2 mRNA was dependent on the dose of YCHT, 500 mg kg (-1) having the greater effect on both Bax and Bcl-2 of mRNA levels. Additionally, YCHT treatment down-regulated both hepatic caspase-3 and -8 activities of BDL rats. This study demonstrates the anti-apoptotic properties of YCHT and suggests a potential application of YCHT in the clinical management of hepatic disease resulting from biliary obstruction.     

Vitamin D2 from irradiated mushrooms significantly increases femur bone mineral density in rats

A method has been optimized for the conversion of ergosterol in mushrooms to vitamin D2, and the vitamin D-enriched mushrooms have been tested for bioavailability of vitamin D2 using a rat model. Femur bone mineral density (BMD) of the experimental group of animals fed with vitamin D2 (1 microg/d) obtained from irradiated mushrooms was significantly increased. Femur BMD of two groups was significantly higher. Femur BMD of the experimental group was significantly elevated compared to initial femur BMD of the study group. Data indicate that vitamin D2 from ultraviolet (UV)-irradiated mushrooms was well absorbed and metabolized in animals.     

维生素D与神经精神疾病

传统观念认为,维生素D作为一种重要的类固醇衍生物,主要维持体内钙磷平衡。近年来其在抑郁症、精神分裂症、多发性硬化症等神经精神疾病的预防治疗作用得到关注。研究还发现维生素D可调节神经营养因子、白细胞介素的表达,这可能与其对神经精神疾病的预防治疗作用机制有关。本文就维生素D在神经精神疾病中的作用作一综述。     

Royal jelly ameliorates insulin resistance in fructose-drinking rats

Royal jelly (RJ) is known to contain excellent nutrition and a variety of biological activities. The present study was designed to investigate the effects of RJ on insulin resistance (hyperinsulinemia) in fructose-drinking rats (FDR; insulin resistance animal model). Male Wistar rats (6 weeks old) received 15% fructose solution in drinking water for 8 weeks. FDR showed significant increases in plasma levels of insulin and triglyceride, Homeostasis Model Assessment ratio (HOMA-R, an index of insulin resistance), and systolic blood pressure, but not blood glucose levels, when compared with control rats. RJ (100, 300 mg/kg, p.o.) treatment for 8 weeks significantly decreased the plasma levels of insulin and triglyceride, HOMA-R, without affecting blood glucose or total cholesterol levels and tended to lower systolic blood pressure. In isolated and perfused mesenteric vascular beds of FDR, RJ treatment resulted in a significant reduction in sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS) and tended to increase the calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS, compared with those in untreated FDR. However, RJ treatment did not significantly affect norepinephrine-induced vasoconstriction or CGRP-induced vasodilation. These results suggest that RJ could be an effective functional food to prevent insulin resistance associated with the development of hypertension.