韩国野山参对大鼠的亚慢性毒性试验

目的通过90 d喂养试验观察韩国野山参提取物对大鼠的亚慢性毒性,为进一步开发野山参的药用及食用价值提供依据。方法 SD大鼠80只,体重60~90 g,随机分为对照组和野山参提取物低、中、高剂量组(2.66 g/kg·BW、5.33g/kg·BW和8.00 g/kg·BW),拌饲给予,每组20只,雌雄各半,连续90 d。每周观察大鼠的体重和进食量,实验中期测定血常规,实验结束时测定血常规和血生化、解剖脏器并计算脏器系数和进行病理学检查。结果结果提示韩国野山参提取物对大鼠体重、进食量、食物利用率、病理组织学指标均未产生明显影响,试验结束时,中剂量组雄鼠嗜酸性细胞百分比高于对照组,雌雄大鼠的总蛋白及白蛋白水平高于对照组,其余血液学指标均无显著变化。结论韩国野山参提取物未见明显的亚慢性毒性损害。     

茶皂素对大鼠亚慢性毒性作用的研究

目的研究茶皂素对大鼠的亚慢性毒性作用。方法选88只SPF级Wistar大鼠随机分为茶皂素高(500 mg/(kg·bw))、中(100 mg/(kg·bw))、低(20 mg/(kg·bw))剂量组和对照组(无菌蒸馏水),每组22只,雌雄各半。每天经口灌胃染毒1次,连续90 d。实验期间,及时记录大鼠一般状况、动物体重及食物消耗量,实验末期进行血常规、血生化和尿液指标检查,解剖动物进行病理观察,计算脏器系数。结果实验期间,各组动物均无死亡情况。低剂量组动物,未见明显异常情况。雄鼠中剂量组的肺脏器系数明显增高(P<0.05),雄鼠高剂量组的体重与对照组相比明显降低(P<0.05),而血常规(白细胞)、脏器系数(脑、脾、肺)与对照组相比明显增高(P<0.05);雌鼠高剂量组的生化指标(谷丙转氨酶、碱性磷酸酶、血清胆碱酯酶)与对照组相比明显增高(P<0.05),而白蛋白与对照组相比降低(P<0.05)。结论本实验显示茶皂素(30%原药)对动物体重有一定影响,Wistar大鼠亚慢性经口毒性实验的最大无作用剂量为20 mg/(kg·bw),观察到有害作用的最小剂量为100 mg/(kg·bw)。     

三七的经口急性毒性及亚慢性毒性研究

目的观察三七的经口急性毒性及亚慢性毒性作用。方法 SD大鼠20只,雌雄各半,采用最大耐受剂量法检测三七的急性毒性作用。80只SD大鼠随机分为阴性对照组、低、中、高剂量组,每组20只,雌雄各半,经口染毒剂量分别为0.000、0.750、2.372、7.500 g/(kg·BW),连续染毒90 d,定期观察一般健康状况,记录体重和摄食量并计算食物利用率,终期检测血液学和血液化学指标,并进行大体解剖,称取重要脏器重量并计算脏/体比值,对高剂量组和阴性对照组大鼠的主要脏器进行组织病理学检查,检查大鼠亚慢性经口毒性作用。结果在14 d观察期内,未出现受试物引起的中毒和死亡情况。雌雄大鼠均外观正常,四肢活动正常。剖检未出现肉眼可见病变。获得三七SD大鼠的经口最大耐受剂量20.25 g/(kg·BW)。大鼠亚慢性经口毒性试验各剂量组动物一般生理体征、行为、外观、皮毛和大小便等均无异常,体重、食物利用率、血液学指标、血液化学指标、脏器重量、脏/体比值、组织病理学检查结果均无与受试物相关的异常。结论在本实验条件下,三七属无毒级物质,大鼠亚慢性经口毒性试验最大未观察到有害作用的剂量(NOAEL)7.500 g/(kg·BW)。     

水飞蓟胶囊的亚慢性毒性研究

目的研究水飞蓟胶囊的亚慢性毒性。方法将80只断乳SD大鼠随机分为3个实验组和1个空白对照组,每组20只,雌雄各半,剂量分别为8.00 g/(kg·bw)、4.00 g/(kg·bw)和2.00 g/(kg·bw),连续喂养91 d。试验期间每周称一次体重,计算食物利用率;试验中期和末期检查大鼠血常规、生化指标;试验结束时处死动物,称量重要脏器重量,计算脏器指数,并对主要脏器进行病理组织学观察。结果试验期间,各组大鼠均未见明显中毒体征,也未见死亡。各实验组大鼠的体重和食物利用率与对照组比较差异无统计学意义。各实验组动物的脏器系数与对照组比较差异均无统计学意义,试验中期、末期血生化和血常规指标与对照组比较差异均无统计学意义。组织病理学未见明显异常。结论在本试验条件下,水飞蓟胶囊无明显亚慢性毒性。     

异丙隆原药慢性毒性研究

目的 为了解异丙隆原药的慢性毒性,提出其慢性最小有害作用剂量(LOAEL)和无害作用剂量(NOAEL).方法 480只SD种雄性和雌性大鼠(体重110～140 g)分为4组,3个染毒组分别喂饲染毒异丙隆原药50.0 mg/(kg·d)(高剂量组)、5.0 mg/(kg·d)(中剂量组)和0.5 mg/(kg·d)(低剂量组),对照组喂饲正常饲料,历时2 a;观察大鼠日常表现、检测体重和饲料消耗量;检查了解解剖、病理、血液学、血液生化和尿液等指标的改变.结果 高剂量组雌性和雄性大鼠的体重增长分别从试验第6周和第11个月开始减慢(P<0.01);高、中两剂量组雄性大鼠肝脏肿大,肝细胞水肿样变性和脂肪变性.结论 异丙隆原药对雌性和雄性大鼠慢性毒性的LOAEL分别为50.0 mg/(kg·d)和5.0 mg/(kg·d),而NAOEL为0.5 mg/(kg·d).     

城市回用水灌溉蔬菜对大鼠的亚慢性毒性研究

目的 研究城市回用水灌溉蔬菜的亚慢性毒性.方法 依据国家标准中食品安全性毒理学评价程序和方法的要求,采用SPF级Wistar大鼠90 d喂养试验对城市回用水灌溉黄瓜和圆白菜的亚慢性毒性进行检测.结果 喂饲期间各组大鼠生长良好,各剂量组大鼠的总增重、总进食量和总食物利用率未见异常改变.实验末期各项血液学指标、血生化指标、尿液指标均在本实验室正常值范围内.各剂量组各种脏器的重量及其脏/体比值与空白、自身井水对照组比较,差异均无统计学意义(P＞0.05).未见有意义的病理改变.结论 城市回用水灌溉黄瓜与圆白菜均未见具有亚慢性毒性.     

锁阳水提物大鼠亚慢性毒性试验研究

目的研究锁阳水提物对大鼠的亚慢性毒性作用。方法按《食品安全性毒理学评价程序和方法》(GB 15193.13—2015)大鼠亚慢性经口毒性试验方法。选取SPF级Wistar大鼠80只,雌雄各半,按体重随机分为对照组及锁阳水提物低、中、高剂量组(2.83、5.66、8.49 g/kg)。大鼠经口灌胃给药,每日一次,连续90 d,灌胃容量13 mL/kg,阴性对照组给予等容量蒸馏水。检测指标包括大鼠的一般临床症状、体重、进食量及食物利用率,血液学及血液生化学检查,组织病理学检查。结果试验期间动物未见明显的中毒症状和死亡。与阴性对照组比较,锁阳水提物各剂量组大鼠体重、进食量、食物利用率差异均无统计学意义(P>0.05);个别剂量组动物血液学及血液生化学检查指标与阴性对照组相比,虽然差异有统计学意义(P<0.05),但值均在实验室正常范围内且无剂量-反应关系,无毒理学意义;雄鼠中、高剂量组血浆凝血酶原时间(prothrombin time,PT)偏高,差异均有统计学意义(P<0.05);雄鼠中剂量组睾丸脏器系数,高剂量组脾脏器系数、睾丸脏器系数、附睾脏器系数偏高,差异均有统计学意义(P<0.05)。组织病理学检查未发现明显异常变化。结论本次试验条件下,锁阳水提物使雄鼠中、高剂量组血浆PT明显增高,使雄鼠中、高剂量组睾丸脏器系数以及高剂量组附睾脏器系数明显增加,大鼠亚慢性经口毒性最大未观察到有害作用剂量(no observed adverse effect level,NOAEL)为2.83 g/kg,最小观察到的有害作用剂量(lowest observed adverse effect level,LOAEL)为5.66 g/kg。     

罗汉松实急性毒性和亚慢性毒性实验研究

目的研究罗汉松实(花托)的急性毒性和亚慢性毒性,并对其安全性进行评价。方法急性毒性试验采用最大给药量法,以160.0 g/(kg·d)的剂量分2次小鼠灌胃200%罗汉松花托汁,观察14 d内的毒性反应。亚慢性毒性试验分3组,实验组分别以20 g/kg和10 g/kg的剂量,SD大鼠灌胃200%罗汉松花托汁,对照组给予蒸馏水,连续灌胃90 d。实验结束时采血测血液学和血生化指标并进行组织病理学检查,计算脏器系数。结果各组动物未见明显毒性反应,也未见死亡。实验组脏器系数、血液学和血生化指标与对照组相比,差异均无统计学意义(P0.05)。组织病理学检查也未见与受试物相关的病理学改变。结论在本实验条件下,未见罗汉松花托汁对实验动物有明显的毒性反应,罗汉松花托安全性较高,可作为食品原料开发利用。     

红参毒理学安全性研究

目的:对红参的食用安全性进行毒理学评价。方法:采用大鼠急性经口毒性试验、遗传毒性试验(Ames试验、小鼠骨髓细胞微核试验、小鼠精子畸形试验)、大鼠30 d喂养试验。结果:雌、雄大鼠经口最大耐受剂量(MTD)均大于19.2 g/kg·bw。3项遗传毒性试验结果均为阴性,表明该受试物无致突变作用。在大鼠30 d喂养试验中,8.0 g/kg.bw,4.0 g/kg·bw及2.0 g/kg·bw 3个剂量组的实验动物均生长发育良好,体重、摄食量、饮水量、血液学、血液生化学、脏器系数及病理组织学相关指标均未见异常变化。结论:红参属于实际无毒物,未见遗传毒性,长期服用是安全的。     

桂花阿胶固体饮料基于动物毒理实验的安全性评价

目的评价桂花阿胶固体饮料的安全性。方法急性经口毒性试验,采用限量法,将大鼠禁食(不禁水)16 h后,经口灌胃给予受试物,剂量为20.0 g/kg·BW,给药后观察14 d;细菌回复突变试验,设5个剂量组,及空白、溶剂、阳性对照组,采用平板参入法,对组氨酸缺陷型4株鼠伤寒沙门氏菌突变型菌株TA97a、TA98、TA100和TA102进行回变菌落计数;哺乳动物红细胞微核试验,设三个剂量组,及环磷酰胺组、阴性对照组,试验采用30 h灌胃法,两次灌胃间隔24 h进行试验,计数骨髓嗜多染红细胞在总红细胞的比例及微核嗜多染红细胞的比率;28 d经口毒性试验,设三个剂量组及一个空白对照组,经口灌胃28 d,观察体质量、食物利用率、血液学指标、血液生化指标及病理检测。结果该样品急性经口毒性试验结果为无毒性,细菌回复突变试验、哺乳动物红细胞微核试验结果均为阴性,28 d经口毒性试验各项指标与空白对照组比较差异无显著性。结论各项试验表明桂花阿胶固体饮料在一定剂量范围内通过系统的体内和体外试验证明其具有食用安全性。     

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。     

牛黄酸对应激大鼠心功能异常变化及心肌损伤的保护作用

以异丙肾上腺素（Ｉｓｏ）诱导的大鼠应激为模型，无创性地研究牛磺酸（Ｔａｕ）对心功能异常变化及心肌损伤的保护作用。与试验前比较，试验后Ｉｓｏ组ＨＲ、ＨＩ、ＣＯ、Ｃ波显著降低，ＲＲ、ＱＳ２、ＰＥＰ、ＺＯ、ＦＴ均显著升高，Ｔａｕ＋Ｉｓｏ组及对照组心功能参数未见显著变化，且Ｉｓｏ组试验后心肌组织有明显损伤，主要表现为肌纤维肿胀、断裂及竹节状病变，而牛磺酸组及对照组试验后心肌组织无显著变化。结果提示，牛磺酸可显著拮抗大鼠的应激性心律失常及心肌收缩、舒张功能的降低，保护心肌组织免受应激损伤     

The Use of Natural Fiber-Rich Food Product Is Safe and Reduces Aberrant Crypt Foci in a Pre-Clinical Model

Background: Colorectal cancer is a highly prevalent disease, requiring effective strategies for prevention and treatment. The present research aimed to formulate a natural fiber-rich food product (NFRFP) and to evaluate its safety, toxicogenetics, and effects on aberrant crypt foci induced by 1,2-dimethyl-hydrazine in a preclinical model. Methods: A total of 78 male Wistar rats were distributed in six experimental groups: negative control, positive control (1,2-Dimethylhydrazine—40 mg/Kg), and four groups fed with 10% NFRFP: NFRFP, pre-treatment protocol, simultaneous treatment, and post-treatment protocol. Results: The NFRFP was shown to be a good source of fibers and did not change biometric, biochemical, hematological, and inflammatory parameters, and did not induce signs of toxicity and genotoxicity/carcinogenicity. NFRFP exhibited a chemopreventive effect, in all protocols, with damage reduction (% DR) of 75% in the comet test. NFRFP reduced the incidence of aberrant crypt outbreaks by 49.36% in the post-treatment protocol. Conclusions: The results suggest the applicability of NFRFP in the human diet due to potential production at an industrial scale and easy technological application in different products, since it could be incorporated in food without altering or causing small changes in final product sensory characteristics.     

低龄大鼠NaF与血清生化和元素含量慢性剂量效应研究

断乳２ 周雄性 Ｗｉｓｔａｒ大鼠５４ 只,饲氟浓度３２、８２、２３２、１５３、４０３ ｍ ｇ／ｋｇ。实验３ 个月。氟引起了体重、血液学、骨骼元素、肝铝、骨铝、血清钙等诸方面的剂量－ 效应的反应。约在８～２３ ｍ ｇ／ｋｇ 饲氟浓度范围内出现许多检测指标的“翻板”现象,呈现与正常对照为基准的相反的含量变化的显著差异。饲氟＞ ２３２ ｍ ｇ／ｋｇ ４ 个组的肝铝成倍增高。肝铝和骨铝与骨氟显著正相关。肝铝与血液学,血清钙,骨钙、铁、磷明显相关,此与铝中毒和铝氟病病人及其鸡模型的研究结果相吻合。认为＞ ２３ ｍ ｇ／ｋｇ 浓度的高氟促进了铝的吸收和蓄积,并主要由铝引起相关的生物效应。     

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.     

Oxidative damage in erythrocytes of adult rats and their suckling pups exposed to gibberellic acid

Gibberellic acid (GA(3)) is a plant growth regulator used in agriculture worldwide. The present study investigated the propensity of GA(3) to induce hematological disorders. Pregnant Wistar rats were randomly divided into two groups: group I served as controls; group II received orally GA(3) (200 ppm) from the 14th day of pregnancy until day 14 after delivery. GA(3) reduced the number of red blood cells, hemoglobin concentration, and hematocrit in suckling rats, while these parameters remained unchanged in their mothers. White blood cells increased in mothers and were unchanged in their pups. Several studies have associated these hematological disorders with oxidative stress. In fact, GA(3) treatment revealed in erythrocytes a significant increase in malondialdehyde levels and a decrease in antioxidant enzyme activities such as superoxide dismutase, catalase, and glutathione peroxidase. Moreover, a significant decline was observed in acetylcholinesterase activity, glutathione, nonprotein thiols, and vitamin C levels.     

Iron-rich drinking water and ascorbic acid supplementation improved hemolytic anemia in experimental Wistar rats

Anemia is a frequent problem in both the primary and secondary health care programs. In contrast, most areas of northeast India are vulnerable to iron toxicity. In the present study, we documented the effect of administration of iron rich water on hemolytic anemia in a Wistar rats’ animal model. Hemolytic anemia was induced by phenyl hydrazine through intraperitoneal route and diagnosed by the lowering of blood hemoglobin. After inducing the hemolytic anemia, 24 Wistar rats (n?=?6 in four groups) were randomly assigned to 1?mg/l, 5?mg/l, and 10?mg/l ferric oxide iron along with 1?mg/ml ascorbic acid administered through drinking water; a control group was treated with iron-free water. The hematological and biochemical parameters, iron levels in liver, spleen, and kidney were estimated after 30?d of treatment. In the group treated with 5?mg/l iron and ascorbic acid, a significant increase of serum iron and ferritin, and a decrease of TIBC (total iron binding capacity) were observed without changes in other biochemical parameters and histopathological findings. However, in the group treated with 10?mg/l iron and ascorbic acid, hematological changes with significantly higher values for white blood cell count, serum glutamic phospho transaminase, serum glutamic oxaloacetic transaminase, alkaline phosphatase, glucose, splenic, and liver iron content, indicate potential toxicity at this supplementation level. Data suggest that the optimum concentration of iron (5?mg/l) and ascorbic acid solution may improve anemic conditions and may be therapeutically beneficial in the treatment of iron deficiency anemia without any negative impact, while 10?mg/l in drinking water seems to be the threshold for the initiation of toxicity.     

Anti-Inflammatory and Antioxidant Effects of Carvacrol on N-Methyl-N′-Nitro-N-Nitrosoguanidine (MNNG) Induced Gastric Carcinogenesis in Wistar Rats

Carvacrol is a dietary polyphenol from Lamiaceae plants that has been shown to possess a wide range of biological activities including antioxidant and antitumor effects. This study aimed to investigate its anti-inflammatory and antioxidant effects on N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) induced gastric carcinogenesis in Wistar rats. Forty-nine rats were randomly assigned to four treatment and three control groups. Over 60 days, MNNG (200 mg/kg BW) was orally applied to animals of groups 1–5 while the rats in groups 2–5 also received different doses of carvacrol (10, 25, 50, and 100 mg/kg BW, respectively) until the end of the experiment. Group 6 rats were treated with 100 mg/kg BW carvacrol and no MNNG whereas group 7 was the control group without any treatment. After the euthanasia of all rats, the inflammatory cytokines and oxidative stress parameters were assessed in the blood and tissues. The expression of caspase 9, Bax, and Bcl-2 proteins in the stomach tissues were investigated through histopathological examinations. Statistically significant differences were observed in the body weight, oxidative stress, and inflammation parameters of groups 1 to 6 compared to group 7 (p ≤ 0.001). Animals in MNNG groups 2 and 3 treated with the low dose carvacrol (10 and 25 mg/kg BW) showed significantly reduced oxidative stress, inflammation, and apoptotic effect compared to animals of the MNNG groups receiving increased doses of carvacrol (50 and 100 mg/kg BW) or no carvacrol. Rats exposed to MNNG exhibited gastric cancer cells in several areas. In the MNNG group receiving 100 mg/kg BW carvacrol, the inflammatory cell infiltration was observed in gastric mucosal and submucosal areas whereas MNNG rats supplemented with 10 and 25 mg/kg BW carvacrol showed no pathological alterations of the gastric cells. The results of this study indicate that significant antioxidant and anti-inflammatory effects induced by carvacrol at doses of 10 and 25 mg/kg BW interfered with gastric carcinogenesis induced by MNNG in Wistar rats as well as provide hepatoprotection. However, high doses of carvacrol (50 and 100 mg/kg BW) increased oxidative stress, inflammation, and apoptosis.     

Effects of gossypol acetate on pituitary-adrenal axis in male albino rats.

Histopathological effects of gossypol acetate (GA) on pituitary-adrenal axis in male Wistar rats were investigated. Sexually mature rats of proven fertility were administered orally with 10 and 25 mg/kg for 4 and 5 weeks, respectively. In both experimental groups, corticotrophs (ACTH cells) of anterior pituitary showed progressive regression. At the 10 mg low-dose treatment for 4 weeks, no significant changes were observed in all the zones of the adrenal gland, while at the same dose for 5 weeks of treatment, cells of zona glomerulosa showed hypertrophy and degranulation as compared to that of control. Cells of zona fasciculata and reticularis showed no significant changes. In the medulla, the thickly granulated cells were degranulated and reduced in number. At the 25 mg treatment, the cells of the zona fasciculata showed hypertrophy and degranulation. The possible mechanism of action of GA is discussed.     

染铅大鼠骨髓NOs和NO的变化

目的 探讨染铅对大鼠骨髓一氧化氮合酶（NOS）活力、一氧化氮（NO）含量的影响及其与血铅相互关系。方法 Wistar大鼠经饮水（加0，18．4，184．0mg/L醋酸铅，分别供对照组、低剂量组、高剂量组自由饮用）染毒，测定骨髓NOS活力、NO含量。结果 NOS活力高剂量染铅组在7d、14d时均较对照组和低剂量组高（P＜0．05），其余时点各组间差异无显著性（P＞0．05），NO含量染铅高剂量组在7d、14d时均较对照组和低剂量组高（P＜0．05），60d各剂量组间差异无显著性（P＞0．05），90d高剂量组显著低于对照组（P＜0．05）。结论 染铅导致大鼠骨髓毒性，引起骨髓NOS活力、NO含量改变，表现为染铅早期骨髓NOS活力、NO含量升高，晚期骨髓NOS活力、NO含量降低；但慢性染铅对骨髓NOS活力、NO含量影响的生理机制有待进一步研究。