Toxicological studies of zinc oxide nanomaterials in rats

In this study, we have evaluated the ability of zinc oxide (ZnO) nanoparticles to induce pulmonary and extrapulmonary toxicities was examined in rats following intratracheal (IT) instillation. Lungs of rats were instilled IT with either phosphate-buffered saline (PBS)?+?1% Tween 80, ZnO nanoparticles, carbonyl iron or quartz particles at a dose of 1 or 5?mg?kg^?1 body weight. Following exposure, bronchoalveolar lavage (BAL) fluid, blood samples and organs including lung, liver, kidneys, heart, pancreas, and brain were collected at 24?h, 1 week, or 1 month of post instillation of nanoparticles and different parameters estimated to assess toxicity. BAL fluid was analyzed for lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) to assess pulmonary toxicity. Exposures to ZnO or quartz particles produced transient dose-dependant increase in BAL fluid LDH and ALP activities at all post exposure periods. Blood samples were analyzed for the tissue damage biomarkers to assess extrapulmonary toxicity. Histopathological examination of lung, liver and kidneys revealed dose-dependent degeneration and necrosis which worsened at 1 week post-instillation periods but recovered at 1 month post instillation. Histopathological examination of rat pancreas, heart, and brain exposed to quartz or ZnO particles showed no marked changes. Data suggest the instillation of ZnO nanoparticles produced a greater pulmonary toxicity in rats comparable with quartz; and extrapulmonary toxicities of these ZnO nanoparticles might be due to translocation into liver and kidney.     

The role of thymoquinone as antioxidant protection on oxidative stress induced by imidacloprid in male and female Swiss albino mice

The aim of the present study was to evaluate the possible protective effects of thymoquinone (TQ), an antioxidant agent, against imidacloprid (IMI)-induced oxidative stress in male and female mice. In total, 48 Swiss Albino male and female mice were fed a standard rodent diet and divided into 3 equal groups: the animals in the control group (vehicle treated) were given corn oil, the second group were orally administered 15 mg/kg/day IMI alone, and the third group were orally administered 15 mg/kg/day IMI and with TQ at 10 mg/kg/day for 21 days. During the experimental period, there were no significant changes between initial body weights and final body weights of IMI treated male and female mice. IMI produced significant increase in blood, liver, kidney, and heart malondialdehyde (MDA) levels and decrease in blood and liver glutathione (GSH) levels. In addition, IMI treatment decreased erythrocyte, liver, and kidney superoxide dismutase (SOD) activity in male mice and decreased erythrocyte and liver SOD activity in female mice. Erythrocyte catalase (CAT) activities were found to be low in male and female mice. However, treatment with TQ reversed IMI-induced oxidative stress, lipid peroxidation, and activities of antioxidant enzymes. Moreover, TQ exhibited protective action against the IMI-induced histopathological changes in tissues of male and female mice. In conclusion, TQ was found to be effective in protecting mice against IMI-induced oxidative stress by enhancing antioxidant defense mechanisms.     

Biochemical changes during larval development of the xanthid crab Rhithropanopeus harrisii. I. Protein,total lipid,alkaline phosphatase,and glutamic oxaloacetic transaminase

Protein, total lipid, and the activities of the enzymes alkaline phosphatase (AP) and glutamic oxaloacetic transaminase (GOT) were measured daily during larval development of the xanthid crab Rhithropanopeus harrisii (Gould). Percent increase in fresh weight was greatest on the first day after each molt. Protein and total lipid per larva increased during the second, third, and fourth zoeal stages, with the most marked increase during the third. When calculated as percent fresh weight, marked accumulation of both protein and total lipid occurred during the third zoeal stage. GOT activity remained stable during the third zoeal stage, but increased significantly during the fourth zoeal stage. AP showed a 4-day cycle of activity apparently related to the molt cycle. It is suggested that increased protein and total lipid content during the third zoeal stage indicate nutritional requirements prior to metamorphosis. Biochemical change may be a more relevant indicator of growth during larval development than either size increase or molt frequency when assessing the value of various diets in the culture of crabs.     

Hepatotoxic and haematological effects of Nigerian Bonny light crude oil in male albino rats

The effect of Bonny light crude oil was assessed in adult albino rats. The rats were administered with 200, 400, and 800?mg/kg of the crude oil orally for 7 days. Fluid intake was measured daily, and the initial and final animal body weight recorded. Oral crude oil at these doses produced no effect on feed and fluid intake between the test groups and the control group. There was a significant decrease in body weight compared to the control group after 7 days of treatment with the different doses of crude oil.

The toxic effects of the liver and hematological effects were assessed. The packed cell volume (PCV) and total white blood cell (WBC) of the 200?mg/kg group were significantly decreased compared to the respective control values. Administration of 200, 400, and 800 mg/kg of Bonny light crude oil, caused a significant dose-dependent increase in glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels, but a significant decrease in the alkaline phosphatase (AP) level compared to the control. Histological examination indicates that crude oil induced severe pathologic changes in the forms of necrosis and oedema.     

Protective effects of curcumin on antioxidant status,body weight gain,and reproductive parameters in male rats exposed to subchronic 2,3,7,8-tetrachlorodibenzo-p-dioxin

The aim of this study was to investigate the effects of curcumin (CUR) on antioxidant status, body weight (BW) gains, and some reproductive parameters in male rats exposed to subchronic doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Thirty-two rats were divided into four groups. The first group was kept as control. The second group (TCDD group) was given TCDD at a dose of 50 ng·kg^?1 BW per day; the third group (CUR group) was treated with CUR at a dose of 80 mg·kg^?1 BW per day. The fourth group (TCDD + CUR group) was given TCDD and CUR at the same doses simultaneously. Malondialdehyde (MDA) levels were significantly increased in the TCDD group. In addition, TCDD exposure decreased liver superoxide dismutase (SOD) activity, catalase (CAT) activities of kidney and brain, glutathione peroxidase (GSH-Px) activities of liver, kidney, and brain, and glutathione levels of liver, kidney, and heart. However, CUR treatment with TCDD exposure decreased MDA levels in all tissues and increased SOD activities of liver, kidney, and brain, CAT activity of heart, and GSH-Px activities of heart and brain. TCDD caused a decrease in BW gain, and CUR partially eliminated this effect of TCDD. In addition, while reproductive organ weights, sperm concentration, and sperm motility tended to decrease with TCDD exposure, these effects tended to be close to normal levels by CUR treatment. In conclusion, CUR was seen to be effective in the treatment and prevention of toxicity induced by subchronic TCDD exposure.     

氯氰菊酯胁迫下鲫鱼肾脏LDH同工酶和血清GOT、SOD活性的变化

为探讨氯氰菊酯对鱼类代谢关键酶活性的影响,以鲫鱼(Carassius auratus)为受试材料,采用室内人工水族箱培养方法进行毒性实验.在急性毒性实验基础上,设置了2、5、10μg·L-13个浓度组和1个对照组进行染毒,分别测定鲫鱼肾脏乳酸脱氢酶同工酶(LDH)、血清谷草转氨酶(GOT)和超氧化物歧化酶(SOD)的活性.结果表明,氯氰菊酯对鲫鱼的96h LC50为20.74μg·L-1.经不同浓度组染毒处理4d后,随着氯氰菊酯浓度的升高,鲫鱼血清GOT活性显著升高(p<0.05);SOD活性则表现为先升高后降低(p<0.05);肾脏LDH同工酶酶谱带型也发生了明显的变化,表现为LDH2、LDH3、LDH4的酶谱带染色浓、谱带较宽.以上结果表明氯氰菊酯对鲫鱼代谢关键酶的活性有一定影响,对鲫鱼的肾脏有一定损伤作用.     

偏钒酸铵对小鼠血清和肝脏转氨酶活力的影响

为了考察偏钒酸铵对小鼠血清和肝脏转氨酶活力的影响,50只小鼠随机分为5组,对照组饮用三重蒸馏水,4个暴露组分别饮用剂量为5、10、15和20 mg·kg-1·d-1的偏钒酸铵,15 d后取血和肝脏样品,测定血清和肝脏中谷丙转氨酶(alanine transaminase,ALT)和谷草转氨酶(aspartate ami...     

三丁基锡和菲对鳗鲡的毒性效应（Toxic Effects of Tributyltin and Phenanthrene on Eels）

采用腹腔注射方式(每周1次,共5次)将生活于淡水或海水中的日本鳗鲡(Anguilla japonica)暴露于三丁基锡氯化物(TBTCl)和菲(Phe),以研究这两种污染物对鳗鲡的毒性效应以及该效应与鱼体所处环境盐度的关系.鳗鲡暴露于TBTCl或Phe1w后,其肝脏和脾脏的组织结构就已发生明显病变,且病变程度随着暴露时间的延长而加剧,其中海水鳗鲡比淡水鳗鲡表现更为严重;但肝体指数(HSI)和性腺组织结构均无明显变化.暴露于TBTCl4～5w后,海水鳗鲡肝脏的谷胱甘肽-S-转移酶(GST)活性比对照组显著升高,而淡水鳗鲡组无明显变化;暴露于TBTCl或Phe3w后,淡水鳗鲡的血浆皮质醇水平显著升高,但海水鳗鲡组无明显变化.TBTCl和Phe对淡水或海水鳗鲡的血浆雌二醇(E2)水平均无明显影响.以上结果表明:有机锡和菲对鳗鲡的肝脏、脾脏有毒性作用,对皮质醇分泌具有内分泌干扰作用,且该效应与暴露时间和鱼体所处环境盐度有关.     

围生期双酚A暴露对子代大鼠脾脏免疫功能的影响

为了研究围生期双酚A(BPA)暴露对子代脾脏免疫功能的影响,选择F344大鼠,按体重随机分为对照、低、中、高4个剂量组(BPA暴露剂量分别为0、4、40、400mg·kg-1·d-1),从雌鼠妊娠第0天开始至子鼠出生后30天,每天灌胃染毒1次,观察子鼠脾脏组织形态学的变化,并采用实时定量PCR检测IL-2、IL-12、IFN-γ、TNF-α4种细胞因子mRNA表达的改变.结果表明,1)与对照组相比,低剂量组子鼠脾重、脾脏指数均显著增加(p<0.05),体重无显著变化(p>0.05);中剂量组子鼠脾脏指数显著增加(p<0.05),体重和脾重无显著变化(p>0.05);高剂量组子鼠体重、脾重均显著降低(p<0.05),脾脏指数无显著变化(p>0.05).2)与对照组相比,各暴露组子鼠脾脏IL-2、IL-12、IFN-γ、TNF-α4种细胞因子mRNA表达均显著降低(p<0.01).以上结果提示,BPA可能能够透过胎盘屏障并通过乳汁传递给子代,降低子代的机体免疫功能.     

Phytochemical screening and toxicological profile of methanolic extract of Picralima nitida fruit-rind (Apocynaceae)

The methanol (M) extract of the fruit-rinds of Picralima nitida (PN) was analyzed phytochemically and evaluated for its toxicity effect in Wistar rats. The rats were administered graded doses (0.75, 1.5, 3, and 6 g kg^?1 p.o) of the extract daily for 6 weeks and the toxicological effect of these varying levels of extract were examined on the serum, hepatic, and renal concentration of biochemical parameters as well as the histopathology of tissue section of these liver, kidney, and lungs. Clinical signs and hematology were also evaluated. Phytochemical analysis revealed that alkaloids and polyphenols were major compounds. Both biochemical and histopathological data presented demonstrate dose-dependent signs of toxicity. Our results show a significant elevation in serum concentration of aspartate amino-transferase, alanine amino-transferase, glucose, creatinine, total cholesterol, and protein with high-dose of PN treatment tested. PN also caused a significant reduction in hepatic malondialdehyde and a slight increase in glutathione concentration at the lowest dose tested. Renal urea level was reduced significantly in test groups. A significant change was observed in the relative weights of the spleen, heart, and kidneys. The total white blood cell count was reduced, whereas the hematocrit level was increased remarkably in animals that received high doses of the extract. The acute toxicity LD₅₀ was estimated at 14.5 and 12.5 g kg^?1 body weight for male and female, respectively. These results show that prolonged usage of this extract at 1.5–6 g kg^?1 dose could cause liver, kidney, and lung injury, while the effect was mild at small dose levels (0.75 g kg^?1). Thus, the extract should be taken with caution bearing in mind that higher doses could affect the liver, kidneys, and lungs.     

Nitrogen and sulphur mustard induced histopathological observations in mouse visceral organs

Nitrogen mustards (HN) and sulphur mustard (SM) are potent alkylating blister inducing chemical warfare agents. Single 1.0 LD50 dose produced a progressive fall in body weight from second day onwards in all groups of mustard agents exposed animals. Histological examination of spleen, liver skin and kidney revealed significant histopathological lesions in nitrogen mustards and sulphur mustard. These lesions include granulovascular degeneration with perinuclear clumping of the cytoplasm of hepatocytes and renal parenchymal cells. Renal lesions were characterized by congestion and hemorrhage. The maximum toxic manifestation were noted in spleen and skin of HN-3 exposed mice while sulphur mustard reported maximum toxicity in liver and kidneys. The study suggests both nitrogen mustards and sulphur mustard to be extremely toxic by percutaneous route based on histopathological observation and can contributed to earlier reported free radical generation by these toxicants.     

饲料中铜暴露对吉富罗非鱼幼鱼血红细胞微核和组织中铜蓄积的影响

为了研究饲料中铜暴露对吉富罗非鱼幼鱼的毒性作用,将1 080条罗非鱼幼鱼暴露于6个浓度梯度的高铜日粮中,通过60 d的暴露试验,测定罗非鱼血红细胞微核变化和组织中铜的蓄积.结果表明,铜在各组织中积累量的顺序依次为:肝脏＞脾脏＞肠道＞鳃＞肌肉,与对照组相比,其中肝脏、脾脏、肠道中铜的含量随着时间和日粮中铜浓度的升高而逐渐升高,而鳃和肌肉中铜含量无显著差异;罗非鱼幼鱼血红细胞微核率、核异常率、总核异常率与日粮中铜的浓度存在一定的剂量—效应关系,并且核异常率高于微核率.     

非暴露式气管滴注3种典型纳米材料对大鼠肝、肾的毒性效应

为探讨纳米二氧化硅(Nano-SiO2)、纳米四氧化三铁(Nano-Fe3O4)和单壁碳纳米管(SWCNTs)对大鼠肝、肾的毒性效应,将49只雄性Wistar大鼠随机分为7组,包括生理盐水对照组,以及3种纳米材料的低剂量组(2mg·mL-1)和高剂量组(10mg·mL-1),采用非暴露式气管滴注法染毒,每2d染毒1次,每次每只0.2mL,共染毒5周,眼眶取血后处死大鼠,称肝、肾重量计算脏器系数,测定大鼠血清中反映肝、肾功能的生化指标,并对肝、肾进行病理学观察.结果表明,1)3种纳米材料均可导致大鼠体重明显降低,但对肝、肾脏器系数无明显影响;2)病理学观察发现,3种纳米材料均可导致大鼠肝细胞轻度脂肪变性,肾脏则无明显改变;3)3种纳米材料均可导致大鼠肝功能异常,部分肝功能指标如谷草转氨酶(AST)、碱性磷酸酶(ALP)、谷丙转氨酶(ALT)等出现显著降低;4)3种纳米材料均可导致大鼠肾功能异常,部分肾功能指标如尿酸(UA)、肌酐(CREA)、尿素氮(BUN)等出现显著升高或降低.以上结果提示,经呼吸道染毒的Nano-SiO2、Nano-Fe3O4和SWCNTs均可对大鼠肝、肾产生一定的毒性效应.     

Fluoride in drinking water exacerbates glomerulonephritis and induces liver damage in ICR-derived glomerulonephritis mice

To evaluate the effects of fluoride on the kidney and the liver of ICR-derived glomerulonephritis (ICGN) mice by using laboratory tests and pathological examinations, fluoride was administered to the ICGN mice at 0, 25, 50, 100, and 150?ppm in drinking water for 4 weeks and to the ICR mice, which have normal kidney function at 0 and 150?ppm. The BUN, creatinine, GOT, and GPT in the serum of each mouse were determined. When a mouse died, the sample from the day closest to the death was assigned for the mean. Pathological changes in the kidney were examined after PAS (periodic acid-Schiff) staining. All of the ICGN mice in the 150?ppm group and one of seven in the 100?ppm group died before the end of week 4, but no ICR mice died. For ICGN mice, the mean value of body weight in the 150?ppm group was significantly lower than those in 0?ppm group and other fluoride-administered groups. The mean values of relative liver and kidney weights in the 100 and 150?ppm groups were significantly lower than those in the control. The mean values of BUN, creatinine, and GPT in the 150?ppm group were significantly higher than those in the control. The thickness of the glomerular capillary wall and the increased mesangial matrix in the kidney were prominent in the fluoride-administered ICGN mice. These results suggested that fluoride severely exacerbated glomerulonephritis and tublar-intestitial changes in ICGN mice.     

Effects of dietary copper exposure on accumulation,growth, and hematological parameters in Cyprinus carpio

The influence of dietary copper (Cu) exposure on accumulation, growth, and hematological parameters was investigated in Cyprinus carpio after sub-chronic ingestion of 0, 250, 500, 750 or 1000?mg?kg^?1 for 60 days. The profile of Cu accumulation among tissues in C. carpio was dependent on the exposure period and Cu concentration. Liver of C. carpio was the predominant storage tissue and the order of Cu accumulation in tissues was liver?>?intestine?> gill?>?kidney?>?muscle. Cu concentration at >125?mg?kg^?1 reduced growth rate, and was inversely related to growth. The RNA?:?DNA ratios were not affected by exposure and there was no correlation between growth rate and RNA?:?DNA ratio in liver and muscle. There were no significant effects of exposure on blood parameters except for magnesium. Cu exposure time and dose increased the serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) activity levels.     

Sub-chronic oral toxicity of acetamiprid in Wistar rats

Acetamiprid is a neoncotinoid insecticide that acts as an agonist to the nicotinic acetylcholine receptor used as insecticide in crops and to control fleas on dogs and cats. The objectives of this study are (1) to evaluate the sub-chronic toxicity of orally administered acetamiprid, (2) to estimate the tissue residue levels and (3) to assess the reactive oxygen species induction in Wistar rats. Clinical signs of toxicity and changes in the haematological parameters were not observed in the acetamiprid-treated groups. Biochemically, increases in the levels of alanine aminotransferase, aspartate aminotransferase, cholesterol and decreases in body weight, feed consumption, reduced glutathione, catalase, superoxide dismutase, glutathione peroxidase, and AchE were observed. Lipid peroxidation was increased in liver and kidney. Acetamiprid residues persisted in liver, kidney, spleen, muscles, brain, fat and histopathology revealed lesions in the liver. The no observable adverse effect level of acetamiprid was found to be ≤55 mg/kg body weight.     

Protective effect of Tamarindus indica fruit pulp extract on collagen content and oxidative stress induced by sodium fluoride in the liver and kidney of rats

Fluorosis is a serious public health problem in many parts of the world. The generation of reactive oxygen species and lipid peroxidation has been considered to play an important role in the pathogenesis of chronic fluoride toxicity. The present study was undertaken to evaluate the protective effect of Tamarindus indica fruit pulp extract on the collagen content and oxidative stress in liver and kidney of fluoride-exposed rats. The first group served as control. The second group received 200 mg L^?1 of sodium fluoride through drinking water. The third and fourth groups received T. indica fruit pulp extract (200 mg kg^?1 body weight) alone and along with fluorinated drinking water respectively, daily by gavage for a period of 90 days. At the end of the experiment, blood samples were collected from all groups, and liver and kidney samples were taken concurrently. Levels of malondialdehyde and glutathione and the activities of superoxide dismutase and catalase were evaluated in the liver and kidney of experimental rats. Furthermore, level of hydroxyproline and histological examination of liver and kidney along with serum biochemical parameters were evaluated. In conclusion, fluoride was determined to cause adverse effects in rats, and the supplementation of tamarind to these animals alleviated the adverse effects of fluoride.     

纳米二氧化钛对小鼠肝、肾细胞DNA的损伤

为探讨纳米TiO2对肝、肾细胞DNA的损伤效应,实验制备了锐钛矿型纳米TiO2颗粒(20～100nm),并采用不同浓度的纳米TiO(20、0.1、0.2、0.4、0.8mg·mL-1)对25只昆明雄性小鼠进行染毒,5d后用单细胞凝胶电泳技术检测小鼠肝、肾细胞DNA的损伤程度.结果表明,随着纳米TiO2染毒浓度的升高,小鼠肝、肾细胞尾部DNA百分率(Tail DNA%)和尾矩(Tail Moment)均呈逐渐升高趋势;对于肝细胞,0.1mg·mL-1组Tail DNA%及Tail Moment与对照组无显著差异(p>0.05),≥0.2mg·mL-1组则显著升高(p<0.05或p<0.01);与肝细胞相比,肾细胞Tai lDNA%及Tail Moment变化更为显著,0.1mg·mL-1组即与对照组存在极显著差异(p<0.01).以上结果表明,纳米TiO2染毒可导致小鼠肝、肾细胞DNA损伤,且随染毒浓度的增加,损伤逐渐加重,呈一定的剂量-效应关系;与肝细胞相比,肾细胞对纳米TiO2更为敏感,较低浓度染毒即可造成DNA损伤.     

Chronic study of arsenic trioxide-induced hepatotoxicity in relation to arsenic liver accumulation in rats

This study measured activities of serum enzymes alkaline phosphatase, acid phosphatase, glutamic oxaloacetic transaminase (SGOT), and glutamic pyruvic transaminase (SGPT), markers of liver function in albino rats after continuous ingestion of arsenic trioxide (As₂0₃). For the study, treated animals were given AS₂O₃ (0.2 mg/100 g/day) orally for 180 days. After the completion of treatment, the blood was collected for the estimation of serum biochemical markers. The results obtained were compared with control group. Data showed a significant increase in SGOT and SGPT activity after 60 days of As₂0₃ administration. The level of alkaline phosphatase and acid phosphatase increased significantly after 90 and 120 days, respectively. Since the elevation of these serum enzymes is an indicator of hepatic damage, data indicate that As₂O₃ produces hepatotoxicity. When taken continuously, arsenic was also deposited in liver and blood and affected the enzymatic pathways. Total accumulated arsenic was determined by HG-AAS at 193.7 nm.     

Effects of aerobic exercise on histopathology and toxicology of ZnO and nano ZnO in male rats

The effects of four weeks of aerobic exercise on histopathological and toxicological effects induced by nano ZnO and ZnO powders in male rats were evaluated. Tissue sections of liver and kidneys of ZnO and nano ZnO rats showed some histopathological changes, which were partly reverted by exercise. ZnO and nano ZnO treatments caused an increase in the level of tumor necrosis factor-α, while the mean of Interleukin 10 was declined. Exercise training enhanced the mean value of and declined mean level of in rats treated with ZnO and nano ZnO. The ZnO and ZnO groups demonstrated the highest means of insulin resistance, low density lipoprotein, cholesterol, triglyceride levels and lower mean value of compared to the other groups, while exercise resulted in improvement in mean of these factors.