玉郎伞多糖诱导人肝肿瘤细胞株BEL7404细胞凋亡

目的研究玉郎伞多糖(YLSPS)对细胞凋亡的影响。方法用MTF法、Hochest荧光染色法及Annexin V-FITC/PI双染法等方法研究YLSPS含药血清对人肝癌细胞株BEL7404的增殖、细胞凋亡及细胞周期的影响。结果YLSPS各剂量组(0.75 g·kg~(-1)、1.50 g·kg~(-1)、3.00 g·kg~(-1))含药血清能明显抑制BEL7404细胞株的增殖,吸光值(D值)分别为0.26±s 0.04、0.22±0.06、0.182±0.026,与NS组(0.43±0.04)比较有显著差异(P<0.01)。YLSPS各剂量组凋亡指数分别为(8.1±1.5)%、(10.8±2.3)%、(11.6±2.9)%,明显高于NS组(P<0.01)。对细胞周期的影响表现为G_2/M期阻滞。结论玉郎伞多糖可诱导BEL7404细胞凋亡,其抗肿瘤活性可能与G_2/M期阻滞有关。     

玉郎伞多糖对四氯化碳诱导大鼠原代肝细胞损伤的保护作用

目的:研究玉郎伞多糖(YLS)对大鼠原代肝细胞损伤的保护作用及其机制。方法:采用IV型胶原酶灌流法分离大鼠肝细胞进行原代培养,用四氯化碳(CCl4)体外诱导肝细胞损伤,检测培养上清液中天门冬氨酸转换酶(AST)和丙氨酸氨基转换酶(ALT)水平,测定肝细胞中丙二醛(MDA)和谷胱甘肽(GSH)含量,MTT法检测细胞存活和增殖活性。结果:YLS(0.125~1.000g.L-1)可明显降低由CCl4升高的肝细胞培养上清液中AST和ALT水平及肝细胞MDA含量,还可提高CCl4降低的肝细胞存活率和GSH含量。结论:提示YLS对大鼠原代培养肝细胞损伤有直接保护作用,该作用可能与其抗氧化作用有关。     

Developmental toxicity study of CBLB502 in Wistar rats

CBLB502 is a derivative of a microbial protein that binds to Toll-like receptor 5. It is demonstrated to reduce inflammatory response from acute stresses, such as radiation in animal models. We determined the potential developmental toxicity of CBLB502 in rats. Four groups of 25 time-mated female Wistar rats/group received subcutaneously 0, 30, 100, or 300 μg/kg/day of CBLB502 from Gestation Days (GD) 6 to 17 at a dose volume of 1.0 mL/kg. Toxicokinetic evaluation was performed on GD 6 and 17. On GD 20 C-section was performed for uterine evaluation and blood samples collected from each dam for immunogenicity assay.Significant decrease in gestation body weight, weight changes and food consumption indicative of maternal toxicity were observed in all dose groups. Also adjusted body weight and weight changes were seen at 300 μg/kg/day. No external, visceral and skeletal abnormalities were observed. The NOAEL for developmental toxicity was estimated to be ≥300 μg/kg/day.     

Toxicological evaluation of potassium perfluorobutanesulfonate in a 90-day oral gavage study with Sprague-Dawley rats

Perfluorobutanesulfonate (PFBS) is a surfactant and degradation product of substances synthesized using perfluorobutanesulfonyl fluoride. A 90-day rat oral gavage study has been conducted with potassium PFBS (K+PFBS). Rats were dosed with K+PFBS at doses of 60, 200, and 600mg/kg-day body weight. The following endpoints were evaluated: clinical observations, food consumption, body weight, gross and microscopic pathology, clinical chemistry, and hematology. In addition, functional observation battery and motor activity assessments were made. Histological examination included tissues in control and 600 mg/kg-day groups. Additional histological examinations were performed on nasal cavities and turbinates, stomachs, and kidneys in the 60 and 200 mg/kg-day groups. No treatment-related mortality, body weight, or neurological effects were noted. Chromorhinorrhea (perioral) and urine-stained abdominal fur were observed in males at 600mg/kg-day. Red blood cell counts, hemoglobin, and hematocrit values were reduced in males receiving 200 and 600mg/kg-day; however, there were no adverse histopathological findings in bone marrow. Total protein and albumin were lower in females at 600mg/kg-day. There were no significant changes in clinical chemistry in either sex. All rats appeared normal at sacrifice. Microscopic changes were observed only at the highest dose in the stomach. These changes consisted of hyperplasia with some necrosis of the mucosa with some squamous metaplasia. These effects likely were due to a cumulative direct irritation effect resulting from oral dosing with K+PFBS. Histopathological changes were also observed in the kidneys. The changes observed were minimal-to-mild hyperplasia of the epithelial cells of the medullary and papillary tubules and the ducts in the inner medullary region. There were no corresponding changes in kidney weights. Clinical chemistry parameters related to kidney function were unchanged. These kidney findings are likely due to a response to high concentration of K+PFBS in tubules and ducts and represent a minimal-to-mild effect. Microscopic changes of an equivocal and uncertain nature were observed in the nasal mucosa and were likely attributable to the route of dosing (oral gavage). The NOAEL for the female rat in this study was 600 mg/kg-day (highest dose of study). The NOAEL for the male rat was 60 mg/kg-day based on hematological effects.     

Biochemical alterations induced by acute oral doses of iron oxide nanoparticles in Wistar rats

Magnetic iron oxide nanoparticles with appropriate surface chemistry have been widely used with potential new applications in biomedical industry. Therefore, the aim of this study was to assess the size-, dose-, and time-dependent effects, after acute oral exposure to iron oxide-30 NP (Fe₂O₃-30), on various biochemical enzyme activities of clinical significances in a female Wistar rat model. Rats were exposed to three different doses (500, 1,000, and 2,000?mg/kg) of Fe₂O₃-30 and Fe₂O₃-Bulk along with control. Fe₂O₃-30 had no effect on growth, behavior, and nutritional performance of animals. Fe₂O₃-30 caused significant inhibition of acetylcholinestrase in red blood cells as well as in brains of treated rats. Further, more than 50% inhibition of total, Na⁺-K⁺, Mg²⁺, and Ca²⁺-ATPases activities, as observed in brains of exposed female rats, may be the result of disturbances in cellular physiology and the iono-regulatory process. Activation of the hepatotoxicity marker enzymes, aspartate aminotransferase and alanine aminotransferase, was recorded in serum and liver, whereas inhibition was observed in kidney. Similarly, enhancement of lactate dehydrogenase activity was observed in serum and liver; however, a decrease in enzyme levels was observed in kidneys of Fe₂O₃-30-treated rats. On the other hand, Fe₂O₃-Bulk did not depict any significant changes in these biochemical parameters, and alterations were near to control. Therefore, this study suggests that exposure to nanosize particles at acute doses may cause adverse changes in animal biochemical profiles. The use of the rat model signifies the correlation with the human system.     

玉郎伞多糖对环磷酰胺致小鼠肝损伤的保护作用

摘 要 目的： 观察玉郎伞多糖（YLSP）对环磷酰胺（CTX）致小鼠肝损伤的治疗作用并探讨其作用机制。方法: 将小鼠随机分为正常对照组（NC）,肝损伤模型组（CTX）,阳性对照组（联苯双酯,BPDC）,YLSP（玉郎伞多糖）高、中、低剂量组。除正常对照组外,其余各组小鼠每天腹腔注射CTX 40 mg·kg^-1,共7 d,建立小鼠肝损伤模型。造模后连续灌胃7 d,观察YLSP对小鼠血清谷氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）和丙二醛（MDA）活性,苏木精 伊红（HE）染色观察小鼠肝脏组织病理学改变。结果:与模型组比较,YLSP各剂量组均能降低小鼠血清中ALT、AST活性及肝组织中MDA的含量;同时能增加肝组织中GSH含量及SOD和GSH Px活性（P<0.05或P<0.01）;HE染色结果显示YLSP能减轻CTX所致的肝组织变性、坏死程度,可减轻小鼠肝组织病理损伤程度。结论: YLSP对CTX所致小鼠肝损伤具有良好的保护作用。     

玉郎伞多糖对肉瘤荷瘤小鼠的体内抗肿瘤作用

目的探讨玉郎伞多糖(YLSPS)对肉瘤荷瘤小鼠的体内抗肿瘤作用及其与环磷酰胺(CTX)联合用药的减毒增效作用。方法昆明小鼠皮下注射肉瘤细胞株S180构建肉瘤荷瘤小鼠动物模型。评价YLSPS不同剂量(0.15、0.30和0.60g·kg-1·d-1)对小鼠胸腺指数(TI)、脾指数(SI)、瘤重及抑瘤率的影响,检测肝组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)的含量。与YLSPS单独用药相比,评价YLSPS不同剂量(0.15、0.30和0.60g·kg-1·d-1)联合CTX(0.01g·kg-1·d-1)用药对小鼠瘤重的影响,检测联合用药对小鼠TI、SI及外周白细胞数的影响。结果YLSPS低、中、高剂量组的TI分别为:(31±s7)、(35±6)和(37±6)mg·g-1,SI分别为:(92±16)、(93±8)和(106±8)mg·g-1。与模型组相比,YLSPS中、高剂量组的TI和SI均显著增高(P<0.01)。YLSPS低、中、高剂量组的平均抑瘤率分别为39.7%、41.3%和52.6%。与模型组比较,YLSPS各剂量组的SOD的活性增高,MDA含量降低。YLSPS各剂量+CTX(0.01g·kg-1·d-1)组,q值在0.85～1.25之间,可明显升高CTX降低的TI、SI及外周血白细胞数。结论YLSPS对肉瘤荷瘤小鼠有明显的抗肿瘤作用,与CTX合用有增效和减毒作用。     

Citrinin and endosulfan induced maternal toxicity in pregnant Wistar rats: pathomorphological study

Dietary exposures to environmental food pollutants such as mycotoxin(s) or pesticide(s) have gained immense significance due to their adverse effects on production and reproduction in animal and human populations. The present investigation was conducted to evaluate the maternal toxicity of citrinin (CIT) and endosulfan administered per os either alone or in combination in pregnant rats during gestational days 6-20. CIT (group I, 10 mg kg(-1) feed, through diet) and endosulfan (group II, 1 mg kg(-1) body weight, by oral intubation) when administered either alone or in combination (group III) in Wistar rats caused clinical signs of toxicity and pathomorphological changes in all the toxin treated groups, the severity being more pronounced in the combination treatment compared with that observed in the control (group IV). The rate of fetal resorptions was highest (22.22%) in the combination treatment followed by endosulfan (16.48%) and CIT (12.50%) treatment groups compared with the control group (3.86%). The histopathological changes such as engorged vasculature, vacuolar degeneration and karyomegaly in liver; congestion, tubular degeneration and cast formation in kidneys; vascular changes and hemosiderosis in uterus and lymphocytic depletion and apoptosis in the lymphoid organs were recorded in the animals of the toxin treated groups. The lesions were consistent and more severe in the combination treatment group compared with the individual treatment groups, suggesting an additive interaction of CIT and endosulfan in inducing maternal toxicity in Wistar rats.     

Effect of oral exposure to acrylamide on biochemical and hematologic parameters in Wistar rats

The toxic effects of ACR monomer include carcinogenesis, cellular genotoxic, and neurotoxicity. In this study, we examined the effect of acrylamide on biochemical and hematologic parameters in Wistar rats and explored the renal and hepatic function of these animals through a complementary anatomopathologic study. For it, thirty female Wistar rats aged 4 weeks and weighing 100?±?10?g were housed six animals per cage and divided as follows: two groups were exposed for 2 months to drinking water containing 5 mg (Group 2) or 10?mg acrylamide (Group 3); one group of 12 rats received the median lethal dose of acrylamide by gavage (Group 4); and the control group (Group 1) received pure water. The results clearly showed that acrylamide affects various biochemical parameters, such as creatinine, urea, and serum globulin levels and the lipid balance, which are directly related to renal and hepatic dysfunction and disruption of the hematologic system. In addition, the data revealed changes in the complete blood count (CBC); significant increases in the number of leukocytes (9.95?±?1.44 and 10.44?±?1.21) and lymphocytes (6.11?±?0.48 and 6.33?±?0.76) in Groups 3 and 4, respectively; and decreases in total protein (88.95?±?6.36), albumin (37.65?±?1.65) and α-1 globulin levels (24.84?±?2.10) in Group 3. The anatomopathologic study confirmed liver damage in the animals administered an acrylamide containing diet compared with those in the control group. The present study confirmed the effects of acrylamide on different hematologic, biochemical and immunologic parameters, with a specific focus on the liver and kidney, and on the induction of neurotoxic disorders. The results showed that oral exposure to acrylamide via drinking water or gavage induces kidney damage, hepatocellular insufficiency and chronic liver disease, resulting in primary immunodeficiency and activation of the immune system following the possible expression of certain immunoreaction genes.     

Acute oral toxicity study of magnesium oxide nanoparticles and microparticles in female albino Wistar rats

Advancements in nanotechnology have led to the development of the nanomedicine, which involves nanodevices for diagnostic and therapeutic purposes. A key requirement for the successful use of the nanoparticles (NPs) in biomedical applications is their good dispensability, colloidal stability in biological media, internalization efficiency, and low toxicity. Therefore, toxicological profiling is necessary to understand the mechanism of NPs and microparticles (MPs). MgO NPs have attracted wide scientific interest due to ease of synthesis, chemical stability and unique properties. However, their toxic effects on humans should also be of concern with the increased applications of nano MgO. The present study was aimed to assess the toxicological potential of MgO NPs in comparison to their micron counterparts in female Wistar rats. Toxicity was evaluated using genotoxicity, histological, biochemical, antioxidant and biodistribution parameters post administration of MgO particles to rats through oral route. The results obtained from the investigation revealed that the acute exposure to the high doses of MgO NPs produced significant (p < 0.01) DNA damage and biochemical alterations. Antioxidant assays revealed prominent oxidative stress at the high dose level for both the particles. Toxicokinetic analysis showed significant levels of Mg accumulation in the liver and kidney tissues apart from urine and feces. Further, mechanistic investigational reports are warranted to document safe exposure levels and health implications post exposure to high levels of NPs.     

玉郎伞多糖对抗结核药诱导肝细胞损伤的保护作用

目的 研究玉郎伞多糖(Y LSPS)对抗结核药诱导的肝细胞损伤的保护作用.方法 将不同浓度的利福平、异烟肼及吡嗪酰胺合用(RFP+ INH+ PZA)作用于人张氏肝细胞,用MTT法检测肝细胞的存活率,以80％ ～ 85％存活率的药物浓度为最佳浓度建立肝细胞损伤模型;给予YLSPS处理后,检测细胞培养上清液中丙氨酸氨基转移酶(ALT)、天门冬氨酸转移酶(AST)和乳酸脱氢酶(LDH)和细胞内丙二醛(MDA)和超氧化物歧化酶(SOD)的浓度.结果 与模型组比较,YLSPS各剂量可明显降低肝细胞培养上清液中的AST、ALT、LDH水平及肝细胞中MDA的含量,升高SOD的水平,且呈剂量依赖性.结论 YLSPS对RFP+ INH+ PZA合用诱导张氏肝细胞损伤具有保护作用,其机制可能与抗氧化和清除自由基的作用有关.     

Anticardiolipin antibodies in spontaneously hypertensive rats (SHR), stroke-prone SHR and normal Wistar rats

1. Anticardiolipin antibodies (ACA) can be detected in the serum of patients with autoimmune disturbances, ischaemic heart disease, myocardial infarction, neurological disorders and other medical conditions. Elevated values of these autoantibodies can be associated with recurrent fetal loss, arterial and venous thrombosis and thrombocytopenia. 2. In the present study, we investigated the presence of ACA in three rat strains, namely normal Wistar rats (WR), spontaneously hypertensive rats Okamoto-Aoki (SHR) and stroke-prone SHR (SHRSP). All animals were examined at four ages: 1, 4, 10 and 12 months of age. Anticardiolipin antibodies were determined by ELISA. 3. Anticardiolipin antibody levels in normal WR, which were used as controls, were lowest at 1 month and increased significantly from the 4th month on. At the prehypertensive age (1 month), ACA levels in SHR and SHRSP were significantly higher compared with control WR, decreased with age and were significantly lower at 4, 10 and 12 months compared with age-matched WR. 4. These differences may be a result of immunological disorders in SHR.     

Toxicological evaluation of l-proline in a 90-day feeding study with Fischer 344 rats

l-proline (l-Pro) is a non-essential amino acid, and has become widely used as supplements and health foods, recently. A subchronic oral toxicity study of l-Pro was conducted with groups of 10 male and 10 female Fischer 344 rats fed a powder diet containing 0%, 0.625%, 1.25%, 2.5% and 5.0% of l-Pro for 90 days. No treatment-related clinical signs and mortality were noted. We observed no clear treatment-related effects with regard to body weight, food intake or urinalysis data. The average daily water intakes of the treated female groups were significantly increased compared to the controls. The hematology (red blood cell parameter) and serum biochemistry (glucose, blood urea nitrogen, creatinine or uric acid) of the treated male and/or female groups were lower than those of the control groups. However, these changes were lacked dose-dependence, and no abnormalities were found in corresponding pathological findings.     

玉郎伞多糖对小鼠急性酒精性肝损伤保护作用的研究

目的:研究玉郎伞多糖对小鼠急性酒精性肝损伤的保护作用。方法:小鼠ig10mL·kg-150%酒精,建立急性酒精性肝损伤模型;测定血清转氨酶、肝组织超氧化物歧化酶活性及甘油三酯含量,并进行病理组织学观察。结果:各剂量玉郎伞多糖能显著降低小鼠血清转氨酶活性和甘油三酯含量,显著提高肝组织超氧化物歧化酶活性,减少肝细胞脂滴数量;高、中剂量玉郎伞多糖可显著减轻酒精性肝损伤小鼠肝细胞的脂肪变性。结论:玉郎伞多糖可减轻酒精对脂肪代谢的影响,对急性酒精性肝损伤有保护作用。     

玉郎伞黄酮对大鼠心肌缺血再灌注损伤的保护作用

目的探讨玉郎伞黄酮(YF)对大鼠心肌缺血再灌注(MIR)引起的氧化性应激损伤的保护作用。方法60只SD大鼠,随机分为假手术组,MIR组,生理盐水组和YF低、中、高剂量组,每组大鼠10只,雌雄各半。结扎冠状动脉左前降支30 min后,再灌注60 min,建立MIR模型。用不同剂量YF在结扎前30 min分别做预处理。再灌注结束后采血,测定血浆中天冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH)、乳酸脱氢酶同工酶1(LDH1)、超氧化物歧化酶(SOD)和丙二醛(MDA)的改变,测量心肌梗死面积。结果YF预处理能明显降低血浆中AST、LDH、LDH1和MDA含量,能提高SOD活性,降低心肌梗死面积。结论YF对大鼠MIR氧化性应激损伤具有显著的保护作用。     

过热蒸汽灭菌松花粉的安全性毒理学评价研究

目的 对过热蒸汽灭菌松花粉进行安全性毒理学评价,为其食用安全性提供科学依据。方法 根据国家标准要求和相关规定,对其进行急性经口毒性试验、细菌回复突变试验、哺乳动物红细胞微核试验、小鼠精子畸形试验和28 d经口毒性试验等毒理学评价试验。结果 受试物最大给予量达10 g·(kg·BW)^-1时,对小鼠未见毒性作用;细菌回复突变试验、哺乳动物红细胞微核试验和小鼠精子畸形试验结果均为阴性,未见该样品有致突变作用;28 d经口毒性试验各项指标均未见明显毒性反应。结论 过热蒸汽灭菌松花粉的急性毒性分级属于实际无毒级,无遗传毒性,在该试验研究剂量和条件下,未见明显毒性作用,具有较高的安全性。     

Critical period and minimum single oral dose of ochratoxin A for inducing developmental toxicity in pregnant Wistar rats

Ochratoxin A (OTA), a potent in vivo teratogen, has been tested in various laboratory animal species. Present investigation was conducted to determine critical dose and critical time for the developmental toxicity of OTA in pregnant Wistar rats after single oral dose administration. OTA at different graded dose levels (2–4 mg/kg body weight) and at different gestation days (6–15), caused variable developmental defects in developing fetuses. OTA at 2.75 mg/kg body weight, dissolved in 0.1 M sodium bicarbonate (vehicle) and administered by oral intubation as a single dose on one of the gestational days 6–15, caused significant maternal toxicity in the dams and various gross, visceral and skeletal anomalies in the fetuses. The major gross malformations were external hydrocephaly, incomplete closure of skull and omphalocele. Internal hydrocephaly, microphthalmia, enlarged renal pelvis and renal hypoplasia were the main internal soft tissue anomalies. Major skeletal defects were developmental defects in skull bones, sternebrae, vertebrae and ribs. The gestational days 6 and 7 were found to be the most critical for the induction of teratogenicity in rats. Single oral dose of 2.75 mg/kg body weight OTA was found to be the minimum effective teratogenic dose in pregnant Wistar rats.     

Toxicological evaluation of Gumiganghwaltang aqueous extract in Crl:CD (SD) rats: 13 weeks oral gavage studies

Gumiganghwaltang is a traditional oriental herbal medicine that has been commonly used to treat colds and inflammatory diseases. Aqueous extract of Gumiganghwaltang (GMGHT) was administrated daily by oral gavage to male and female rats for 13 weeks. A dose of 2000 mg/kg/day was selected as a maximum, and doses of 1000 and 500 mg/kg/day were determined as medium and low doses, respectively. No treatment-related clinical signs or mortality were observed in the treatment group. We observed no clear treatment-related effects with regard to body weight, food consumption, ophthalmology, hematology, or urinalysis data. The serum biochemistry values for sodium and chloride in the treated male and female groups (1000 mg/kg/day) were lower than in those treated with the vehicle control. However, these changes lacked dose dependence, and no abnormalities were found in corresponding pathological findings. Our results indicated that the no-observed-adverse-effect-level (NOAEL) for GMGHT was determined to be a dietary dose of over 2000 mg/kg/day for both sexes under the present experimental conditions.