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p53-dependent apoptosis contributes to di-(2-ethylhexyl) phthalate-induced hepatotoxicity
2016
Ha, Mei | Wei, Li | Guan, Xie | Li, Lianbing | Liu, Changjiang
Di-(2-ethylhexyl) phthalate (DEHP) is used extensively in many personal care and consumer products, resulting in widespread non-occupational human exposure through multiple routes and media. DEHP has various deleterious effects including hepatotoxicity. p53 protein is a central sensor in cell apoptosis. In order to clarify the roles of p53 in DEHP-induced hepatotoxicity, Sprague–Dawley (SD) rats were dosed daily with DEHP by gavage for 30 days; BRL cells (rat liver cell line) were treated with DEHP for 24 h after pretreatment with NAC or small interfering RNA (siRNA). Results indicated that after exposure to DEHP, hepatic histological changes such as hepatocyte edema, vacuolation and hepatic sinusoidal dilation, and increased apoptosis index were observed. In the liver, DEHP induced oxidative stress and DNA damage, which activated p53 in vivo and in vitro. Pretreatment with NAC significantly reduced ROS level and p53 expression in BRL cells. The suppressed Mdm2 also contributed to p53 accumulation. Activated p53 mediated hepatocyte apoptosis via the intrinsic mitochondrial pathway, inhibiting anti-apoptotic Bcl-2 and Bcl-xL and inducing pro-apoptotic Bax, cytochrome c and caspases. In p53-silenced BRL cells, hepatocyte apoptosis mediated by p53 was attenuated. PCNA protein level was upregulated after p53 gene silencing. However, the Fas/FasL apoptotic pathway did not exhibit activated signs in DEHP-caused hepatotoxicity. Taken together, DEHP-caused oxidative stress and Mdm2 downregulation contribute to p53 activation. The p53-dependent apoptotic pathway plays critical and indispensable roles in DEHP-induced hepatotoxicity, while the Fas/FasL pathway does not involve in this molecular event.
显示更多 [+] 显示较少 [-]Genotoxic and Histopathological Effects of Olive-Mill Wastewater on Lepomis gibbosus
2016
Koca, Serdar | Koca, Yucel Basimoglu
In this study, the genotoxic and histopathological effects of olive-mill wastewater (OMW) on the tissue cells of Lepomis gibbosus were investigated. The fish were caught from Topçam dam lake (Çine/Aydın) and were exposed to the wastewater in 50-L aquariums which contained 0.5 % OMW for 3–5 and 7 days. In genotoxic investigations, a statistically significant increase was observed in the frequency of micronuclei in the L. gibbosus in experimental groups. As a result of the exposure to OMW, histopathological findings which showed a parallel increase with the amount of exposure in the gill, liver and muscle tissues were determined. In the gills, disruption of lamellae shape, shortening and breakage of primary and secondary lamellae, fusion and branching, separation in the secondary lamellae epithelium, ballooning dilation, hyperplasia in support cells and increase in mucus cells were observed. In the parenchyma of the liver, a difference in local staining, focal necrosis, haemorrhaging in necrotic areas, oedema of blood vessels, expansion in sinusoids, congestion and dilation in portal veins, deterioration of vessel walls, cytoplasmic vacuolization in hepatocytes, pyknotic nuclei, decrease in glycogen storage in hepatocytes near the central vein and aggregates of melanomacrophages were also observed. The necrosis in muscle bundles, widespread oedema between myofibrils, degeneration and separation in some muscle groups, decrease in glycogen content, intramuscular oedema and atrophy in the myofibers were determined in the experimental groups.
显示更多 [+] 显示较少 [-]Toxicity of 3,5,6-trichloro-2-pyridinol tested at multiple stages of zebrafish (Danio rerio) development
2016
Suvarchala, Gonuguntla | Philip, Gundala Harold
Organophosphate compounds (OP) are widely used throughout the world for pest control. 3,5,6-Trichloro-2-pyridinol (TCP) is a primary metabolite of two OP compounds namely CP and triclopyr. This study is carried out to know whether a metabolite of parent compound is doing well or harm to biota. The potential effect of TCP was evaluated on development as destabilization of any events transpiring during embryogenesis could be deleterious. To determine this, 4-hpf zebrafish embryos were exposed to five concentrations of TCP (200, 400, 600, 800, 1000 μg/L) or 99.5 % acetone (solvent control). Different early life-stage parameters were observed at four different developmental stages, 24, 48, 72 and 96 hpf. TCP-treated embryo/larvae showed increased mortality, delay in hatching time and decrease in percentage of hatched embryos. Reduction in heartbeat rate, blood flow and body and eye pigmentation was noticed in a dose-dependent manner. Pericardial and yolk sac edema were most severe malformations caused by TCP. Along with this crooked spine/notochord, tail deformation was noticed in hatched and unhatched embryos. The malformations observed provide a good starting point for examination of the molecular mechanisms that are affected during development by TCP. Results gain significance as TCP, which is a breakdown product, appears to be more toxic during development compared to parent compound, CP (our earlier publication).
显示更多 [+] 显示较少 [-]Acute and short-term developmental toxicity of cyhalofop-butyl to zebrafish (Danio rerio)
2016
Cao, Fangjie | Liu, Xiaoshan | Wang, Chengju | Zheng, Mingqi | Li, Xuefeng | Qiu, Lihong
Cyhalofop-butyl is an aryloxyphenoxypropionate post-emergence herbicide widely used around the world in agriculture. The acute toxicity of cyhalofop-butyl to embryos, larvae (12 and 72 h post-hatching), and adult zebrafish, as well as the short-term developmental toxicity of cyhalofop-butyl to embryo and sac-fry stages, was tested. The results showed that the 96-h LC₅₀ values of cyhalofop-butyl to embryos, 12 h post-hatching larvae, 72 h post-hatching larvae, and adult fish were 2.03, 0.58, 1.42, and 3.49 mg/L, respectively, suggesting zebrafish early life stages were more sensitive to cyhalofop-butyl than adult stage. Cyhalofop-butyl would inhibit the spontaneous movement, heartbeat, hatching rate of embryos, and the body length of surviving larvae of zebrafish at 1.00 mg/L or higher concentrations. Morphological abnormalities, including pericardial edema, yolk sac edema, deformation of tail, and deformation of spine, were induced by cyhalofop-butyl. The results indicated that cyhalofop-butyl had significant negative impacts on zebrafish at different life stages, and spontaneous movement and hatching rate were sensitive endpoints for assessing short-term developmental toxicity of cyhalofop-butyl.
显示更多 [+] 显示较少 [-]Comparative sensitivity among early life stages of the South American toad to cypermethrin-based pesticide
2016
Svartz, Gabriela | Aronzon, Carolina | Pérez Coll, Cristina
Cypermethrin is one of the most widely used pesticides due to its low mammalian and bird toxicity, but it is extremely toxic to aquatic organisms. The aim of the present study was to evaluate the toxicity of a commercial formulation of cypermethrin on the embryo–larval development of Rhinella arenarum. An ecological risk assessment based on the hazard quotient (HQ) approach was performed. The results showed that cypermethrin toxicity was stage-dependent and dramatically increased during the larval period. Thus, larvae were more sensitive than embryos, obtaining at the end of the experiment a 336-h median lethal concentration (LC50) of 0.65 μg cypermethrin/L. Cypermethrin exposure caused morphological abnormalities such as general underdevelopment, edema, gill malformations, and behavioral alterations as hyperkinesia and spasmodic contractions. The 168-h teratogenic index was 5, implying a high risk for embryos to be malformed in the absence of significant embryonic lethality. Based on the results of the toxicity effects and the ecological risk assessed (HQ for chronic exposure > level of concern), this pesticide should be considered as a direct (effects on survival) or indirect (severe sublethal effects) risk for conservation purposes of this amphibian in agroecosystems.
显示更多 [+] 显示较少 [-]Histopathological study of toxic effects of carbaryl on digestive tract of Bufotes variabilis (Anura: Bufonidae)
2016
Çakıcı, Özlem
Due to the negative effects of pesticide usage in environment, i.e., decline in amphibian populations, this study was designed to examine histopathologic changes following carbaryl exposure for 96 h in the digestive tract of variable toad, Bufotes variabilis. After exposure to single doses of carbaryl (low dose 50 μg/g, medium dose 100 μg/g, and high dose: 200 μg/g), the toads were euthanized and dissected and digestive tract samples were quickly removed. Histopathology revealed esophageal vacuolization and necrosis in esophageal cells. Hemorrhage was also observed in the esophagus. In the stomach, necrosis in the glandular epithelium, congested blood vessels, edema among gastric glands, dilated tips of the mucosal epithelial layer, gastric glandular atrophy, and hemorrhage were found. In the intestine, edema within villi, hemorrhage, inflammation, vacuolization, and necrosis in epithelial cells of villi were detected. This study clearly showed that carbaryl caused adverse effects on the digestive tract of B. variabilis in all dose groups.
显示更多 [+] 显示较少 [-]The cardioprotective effects of L-carnitine on rat cardiac injury, apoptosis, and oxidative stress caused by amethopterin
2016
Tousson, Ehab | Hafez, Ezar | Zaki, Somia | Gad, Amani
Amethopterin is used as a chemotherapeutic agent, and its antioxidant activity is used to treat many cancer types. This study aimed to study the ameliorating effect of L-carnitine against amethopterin-induced cardiac injury and oxidative stress in male rats. Sixty male albino rats were equally divided into six groups; the first and second groups were the control and L-carnitine groups, respectively, while the third group was treated with amethopterin rat group; the fourth and fifth groups were co-treated and post-treated with amethopterin rat with L-carnitine, respectively, and the sixth group was self-treated with amethopterin rat group. Cholesterol, triglycerides, low-density lipoprotein (LDL), glutathione, and total protein levels in amethopterin group showed a significant decrease when compared with control group, while high-density lipoprotein (HDL), glutamic oxaloacetic transaminase (GOT), malondialdehyde (MDA), catalase, and nitric oxide (NO) levels in amethopterin group showed a significant increase when compared with control group. Cholesterol, triglycerides, LDL, GOT, MDA, and catalase levels in the self-treated group showed a significant increase when compared with amethopterin group, while glutathione, total protein, and NO levels in the self-treated group showed significant decrease when compared with amethopterin group. Many of abnormalities as moderate hydrophobic changes of myofibrillar structure with striations, myocardial atrophy, cytoplasmic vacuoles, edema, and leukocyte infiltration were detected in cardiac tissues in amethopterin rat group. A significant increase of the apoptotic protein p53 and CD68 immunoreactivity, despite a significant decrease in the antiapoptotic Bcl–2 proteins after amethopterin injection when compared with control group, was observed. Treatment (co and post) with L-carnitine improved the biochemical, histopathological, and immunohistochemical alterations in the heart treated with amethopterin.
显示更多 [+] 显示较少 [-]Toxicopathic changes and genotoxic effects in liver of rat following exposure to diazinon
2016
Ezzi, Lobna | Haouas, Zohra | Salah, Imen Belhadj | Sakly, Amina | Grissa, Intissar | Chakroun, Sana | Kerkeni, Emna | Hassine, Mohsen | Mehdi, Meriem | Cheikh, Hassen Ben
In general, people may come in contact with mixtures of insecticides through domestic use, consumption of contaminated food or drinks, and/or living close to treated areas. We analyzed the toxic effects of diazinon on histological structure of liver and hematological parameters in male rats. DNA-damaging potential of diazinon was also investigated using the comet assay in blood cells and the micronucleus test in bone marrow. Two groups of six male rats orally received different amounts of diazinon: 1/50 and 1/25 LD ₅₀ for 4 weeks (5 day/week). The present study showed that diazinon caused hypertrophy of sinusoids, central vein, and portal triad, in addition to the formation of oedema, vacuoles, hemorrhage, necrosis, and lymphoid infiltration in rats’ liver. A significant decrease in red blood cells, hemoglobin, hematocrite levels, and platelet counts was observed in the treated groups. However, the white blood cell count increased. Micronucleus test results revealed aneugenic effects of diazinon. Furthermore, we noticed an increase in comet tail length in treated groups. So, the comet assay confirmed the genotoxic potential of diazinon in vivo. On the assumption that all alterations observed in rats could be observed in human, it is necessary to raise the awareness about the health risk posed by this insecticide.
显示更多 [+] 显示较少 [-]Homogeneous static magnetic field of different orientation induces biological changes in subacutely exposed mice
2016
Milovanovich, Ivan D. | Ćirković, Saša | De Luka, Silvio R. | Djordjevich, Drago M. | Ilić, Andjelija Ž | Popović, Tamara | Arsić, Aleksandra | Obradović, Danilo D. | Oprić, Dejan | Ristić-Djurović, Jasna L. | Trbović, Aleksa M.
It has been shown that static magnetic field (SMF) of moderate intensity produces considerable impact on biological systems. SMF can be homogeneous or inhomogeneous. In many studies, inhomogeneous SMF was employed. Aware that inhomogeneous SMF could result in experimental variability, we investigated the influence of a vertical homogeneous SMF of different orientation. Male Swiss-Webster 9- to 10-week-old mice were subacutely exposed to upward- and downward-oriented SMF of 128 mT generated by a cyclotron for 1 h/day during a 5-day period. We found that SMF affected various organs and that these effects were, to some degree, dependent on SMF orientation. Both upward- and downward-oriented SMF caused a reduction in the amount of total white blood cells (WBC) and lymphocytes in serum, a decrease of granulocytes in the spleen, kidney inflammation, and an increase in the amount of high-density lipoprotein (HDL). In addition, upward-oriented SMF caused brain edema and increased spleen cellularity. In contrast, downward-oriented SMF induced liver inflammation and a decrease in the amount of serum granulocytes. These effects might represent a specific redistribution of pro-inflammatory cells in blood and among various organs. It appears that homogeneous SMF of 128 mT affected specific organs in the body, rather than simultaneously and equally influencing the entire body system.
显示更多 [+] 显示较少 [-]Acute toxicity and histopathological effects of naproxen in zebrafish (Danio rerio) early life stages
2016
Li, Qian | Wang, Peipei | Chen, Ling | Gao, Hongwen | Wu, Lingling
Zebrafish (Danio rerio) embryos and larvae were selected to investigate the potential risk and aquatic toxicity of a widely used pharmaceutical, naproxen. The acute toxicity of naproxen to embryos and larvae was measured, respectively. The histopathology was investigated in the liver of zebrafish larvae after 8-day embryo-larvae exposure to naproxen. The values of 96-h LC₅₀ were 115.2 mg/L for embryos and 147.6 mg/L for larvae, indicating that zebrafish embryos were more sensitive than larvae to naproxen exposure. Large suites of symptoms were induced in zebrafish (D. rerio) early life stages by different dosages of naproxen, including hatching inhibition, lower heart rate, and morphological abnormalities. The most sensitive sub-lethal effect caused by naproxen was pericardial edema, the 72-h EC₅₀ values of which for embryos and larvae were 98.3 and 149.0 mg/L, respectively. In addition, naproxen-treated zebrafish larvae exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. The results indicated that naproxen is a potential threat to aquatic organisms.
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