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  • 1.

    【2hr】Chromium Exposure and Hygienic Behaviors in Printing Workers in Southern Thailand

    包量

    机译 泰国南部印刷工人中的铬暴露和卫生行为
    摘要：Objectives. The main objective of this study was to assess the chromium exposure levels in printing workers. The study evaluated the airborne, serum, and urinary chromium levels and determines any correlation between level of chromium in specimen and airborne chromium levels. Material and Methods. A cross-sectional study was conducted with 75 exposed and 75 matched nonexposed subjects. Air breathing zone was measured by furnace atomic absorption spectrophotometer. Serum and urine samples were collected to determine chromium levels by graphite furnaces atomic absorption spectrometer chromium analyzer. Results and Discussion. The printing workers' urinary chromium levels (6.86 ± 1.93 μg/g creatinine) and serum chromium levels (1.24 ± 1.13 μg/L) were significantly higher than the control group (p < 0.001 and p < 0.001). Work position, duration of work, personal protective equipment (PPE), and personal hygiene were significantly associated with urinary chromium level and serum chromium levels (p < 0.001 and p < 0.001). This study found a correlation between airborne chromium levels and urinary chromium levels (r = 0.247, p = 0.032). A multiple regression model was constructed. Significant predictors of urinary and serum chromium levels were shown in this study. Conclusion. Improvements in working conditions, occupational health training, and PPE use are recommended to reduce chromium exposure.
  • 2.

    【2hr】Acute β-N-Methylamino-L-alanine Toxicity in a Mouse Model

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    机译 小鼠模型中的急性β-N-甲基氨基-L-丙氨酸毒性
    摘要：The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) is considered to be an “excitotoxin,” and its suggested mechanism of action is killing neurons. Long-term exposure to L-BMAA is believed to lead to neurodegenerative diseases including Parkinson's and Alzheimer's diseases and amyotrophic lateral sclerosis (Lou Gehrig's disease). Objectives of this study were to determine the presumptive median lethal dose (LD50), the Lowest-Observed-Adverse-Effect Level (LOAEL), and histopathologic lesions caused by the naturally occurring BMAA isomer, L-BMAA, in mice. Seventy NIH Swiss Outbred mice (35 male and 35 female) were used. Treatment group mice were injected intraperitoneally with 0.03, 0.3, 1, 2, and 3 mg/g body weight L-BMAA, respectively, and control mice were sham-injected. The presumptive LD50 of L-BMAA was 3 mg/g BW and the LOAEL was 2 mg/g BW. There were no histopathologic lesions in brain, liver, heart, kidney, lung, or spleen in any of the mice during the 14-day study. L-BMAA was detected in brains and livers in all of treated mice but not in control mice. Males injected with 0.03 mg/g BW, 0.3 mg/g BW, and 3.0 mg/g BW L-BMAA showed consistently higher concentrations (P < 0.01) in brain and liver samples as compared to females in those respective groups.
  • 3.

    【2hr】Neuroprotective Effects of Alpha-Mangostin on MPP+-Induced Apoptotic Cell Death in Neuroblastoma SH-SY5Y Cells

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    机译 α-Mangostin对神经母细胞瘤SH-SY5Y细胞中MPP +诱导的凋亡细胞死亡的神经保护作用。
    摘要：In vitro studies have shown that extracts from mangosteen (Garcinia mangostana Linn.) act as antioxidants and cytoprotective agents against oxidative damage. The protective effect of alpha-mangostin, the major xanthone found in the pericarp of the mangosteen, in cellular models of Parkinson's disease (PD), has not been investigated. This study aims to investigate whether alpha-mangostin could protect SH-SY5Y neuroblastoma cells from MPP+-induced apoptosis. The effects of alpha-mangostin on MPP+-induced cell death were evaluated with a cell viability assay, staining for nuclear DNA morphology, flow cytometry for apoptotic cells and reactive oxygen species (ROS) production, quantitative real-time PCR for the expression of p53, Bax, and Bcl-2, and western blot analysis for cleaved caspase-3. Concomitant treatment with alpha-mangostin attenuated the effect of MPP+ on cell viability and apoptotic cell death. Alpha-mangostin reduced ROS formation induced by MPP+. Bax/Bcl-2 expression ratio and expression of p53 were significantly lower in cells cocultured with alpha-mangostin and MPP+. The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP+ treatment alone. Our data suggest that cytoprotection of alpha-mangostin against MPP+-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation.
  • 4.

    【2hr】The Protective Effects of Nigella sativa and Its Constituents on Induced Neurotoxicity

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    机译 苜蓿及其成分对神经毒性的保护作用
    摘要：Nigella sativa (N. sativa) is an annual plant and widely used as medicinal plant throughout the world. The seeds of the plant have been used traditionally in various disorders and as a spice to ranges of Persian foods. N. sativa has therapeutic effects on tracheal responsiveness (TR) and lung inflammation on induced toxicity by Sulfur mustard. N. sativa has been widely used in treatment of various nervous system disorders such as Alzheimer disease, epilepsy, and neurotoxicity. Most of the therapeutic properties of this plant are due to the presence of some phenolic compounds especially thymoquinone (TQ), which is major bioactive component of the essential oil. The present review is an effort to provide a comprehensive study of the literature on scientific researches of pharmacological activities of the seeds of this plant on induced neurotoxicity.
  • 5.

    【2hr】Acute Methotrexate Ingestions in Adults: A Report of Serious Clinical Effects and Treatments

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    机译 成人急性甲氨蝶呤的摄入：严重的临床疗效和治疗方法的报告
    摘要：Objective. Limited reported data have reports effects after acute ingestion of methotrexate. Treatment recommendations do not differentiate between exposure routes. Our objective was to determine the frequency of significant toxicity effects and use of therapy after methotrexate ingestion in adults. Methods. We performed a retrospective study on adult cases reported to 6 poison centers over 6 years (2000–2005) which exceed 180,000 exposures/year. Variables collected included demographics, dosages ingested, coingestions, clinical effects, and therapies with outcomes. Results. Sixty-three patients examined over the 6-year period met inclusion criteria. No patient in the series received dialysis or died. The mean dose ingested for all patients was 24 mg (range 2.5–100 mg) and the mean dose for suicidal ingestions was 47.5 mg (12.5–100 mg). The most common clinical effects were abdominal pain, oral irritation, throat irritation, nausea, dizziness, and headache. Nine patients received folinic acid and 3 patients received sodium bicarbonate. No patient developed renal failure, bone marrow suppression, seizure, or coma. No patient died or received dialysis. Conclusion. In our series of patients from 6 poison centers over six years, 63 cases of acute adult methotrexate ingestions were reported. Methotrexate toxicity from ingestion in adults was uncommon and rarely toxic.
  • 6.

    【2hr】Toxicological Study of Ocimum sanctum Linn Leaves: Hematological, Biochemical, and Histopathological Studies

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    机译 乌头圣菩提叶的毒理学研究：血液学，生化和组织病理学研究
    摘要：The present study was aimed to study the acute and subacute toxicity studies with orally administered 50% ethanolic leaves extract of Ocimum sanctum Linn (OSE). In acute toxicity tests, four groups of mice (n = 6/group/sex) were orally treated with doses of 200, 600, and 2000 mg/kg, and general behavior, adverse effects, and mortality were recorded for up to 14 days. In subacute toxicity study, rats received OSE by gavage at the doses of 200, 400, and 800 mg/kg/day (n = 6/group/sex) for 28 days, and biochemical, hematological, and histopathological changes in tissues (liver, kidney, spleen, heart, and testis/ovary) were determined. OSE did not produce any hazardous symptoms or death and CNS and ANS toxicities in the acute toxicity test. Subacute treatment with OSE did not show any change in body weight, food and water consumption, and hematological and biochemical profiles. In addition, no change was observed both in macroscopic and microscopic aspects of vital organs in rats. Our result showed that Ocimum sanctum extract could be safe for human use.
  • 7.

    【2hr】Conditioned Medium Reconditions Hippocampal Neurons against Kainic Acid Induced Excitotoxicity: An In Vitro Study

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    机译 条件培养基修复海藻神经元抵抗海藻酸诱导的兴奋性毒性：一项体外研究。
    摘要：Stem cell therapy is gaining attention as a promising treatment option for neurodegenerative diseases. The functional efficacy of grafted cells is a matter of debate and the recent consensus is that the cellular and functional recoveries might be due to “by-stander” effects of grafted cells. In the present study, we investigated the neuroprotective effect of conditioned medium (CM) derived from human embryonic kidney (HEK) cells in a kainic acid (KA) induced hippocampal degeneration model system in in vitro condition. Hippocampal cell line was exposed to KA (200 µM) for 24 hrs (lesion group) whereas, in the treatment group, hippocampal cell line was exposed to KA in combination with HEK-CM (KA + HEK-CM). We observed that KA exposure to cells resulted in significant neuronal loss. Interestingly, HEK-CM cotreatment completely attenuated the excitotoxic effects of KA. In HEK-CM cotreatment group, the cell viability was ~85–95% as opposed to 47% in KA alone group. Further investigation demonstrated that treatment with HEK-CM stimulated the endogenous cell survival factors like brain derived neurotrophic factors (BDNF) and antiapoptotic factor Bcl-2, revealing the possible mechanism of neuroprotection. Our results suggest that HEK-CM protects hippocampal neurons against excitotoxicity by stimulating the host's endogenous cell survival mechanisms.
  • 8.

    【2hr】Impairment of Hepatic and Renal Functions by 2,5-Hexanedione Is Accompanied by Oxidative Stress in Rats

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    机译 2,5-己二酮对肝肾功能的损害与氧化应激相伴
    摘要：2,5-Hexanedione (2,5-HD) is the toxic metabolite of n-hexane which is widely used as solvent in numerous industries. The present study elucidated the precise mechanism of 2,5-HD in hepatorenal toxicity by determining the involvement of oxidative stress in rats. Adult male Wistar rats were exposed to 0, 0.25, 0.5, and 1% 2,5-HD in drinking water for 21 days. Exposure to 2,5-HD caused liver and kidney atrophy evidenced by significant elevation in serum aminotransferases, alkaline phosphatase, albumin, bilirubin, urea, creatinine, and electrolytes levels compared with control. The marked dose-dependent increase in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) was accompanied with significant decrease in high-density lipoprotein (HDL) levels in 2,5-HD-exposed animals when compared with the control. Administration of 2,5-HD significantly diminished glutathione (GSH) level but increased the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione-S-transferase (GST) concomitantly with marked elevation in hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels in liver and kidney of the treated groups compared with control. These findings suggest that undue exposure to 2,5-HD at environmentally relevant levels may impair liver and kidney functions through induction of oxidative stress.
  • 9.

    【2hr】Ecotoxicological and Genotoxic Evaluation of Buenos Aires City (Argentina) Hospital Wastewater

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    机译 布宜诺斯艾利斯市（阿根廷）医院废水的生态毒理学和遗传毒性评估
    摘要：Hospital wastewater (HWW) constitutes a potential risk to the ecosystems and human health due to the presence of toxic and genotoxic chemical compounds. In the present work we investigated toxicity and genotoxicity of wastewaters from the public hospital of Buenos Aires (Argentina). The effluent from the sewage treatment plant (STP) serving around 10 million inhabitants was also evaluated. The study was carried out between April and September 2012. Toxicity and genotoxicity assessment was performed using the green algae Pseudokirchneriella subcapitata and the Allium cepa test, respectively. Toxicity assay showed that 55% of the samples were toxic to the algae (%I of growth between 23.9 and 54.8). The A. cepa test showed that 40% of the samples were genotoxic. The analysis of chromosome aberrations (CA) and micronucleus (MN) showed no significant differences between days and significant differences between months. The sample from the STP was not genotoxic to A. cepa but toxic to the algae (%I = 41%), showing that sewage treatment was not totally effective. This study highlights the need for environmental control programs and the establishment of advanced and effective effluent treatment plants in the hospitals, which are merely dumping the wastewaters in the municipal sewerage system.
  • 10.

    【2hr】High Content Imaging and Analysis Enable Quantitative In Situ Assessment of CYP3A4 Using Cryopreserved Differentiated HepaRG Cells

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    机译 高含量的成像和分析能够使用冷冻保存的分化的HepaRG细胞进行CYP3A4的定量原位评估
    摘要：High-throughput imaging-based hepatotoxicity studies capable of analyzing individual cells in situ hold enormous promise for drug safety testing but are frequently limited by a lack of sufficient metabolically competent human cells. This study examined cryopreserved HepaRG cells, a human liver cell line which differentiates into both hepatocytes and biliary epithelial cells, to determine if these cells may represent a suitable metabolically competent cellular model for novel High Content Analysis (HCA) applications. Characterization studies showed that these cells retain many features characteristic of primary human hepatocytes and display significant CYP3A4 and CYP1A2 induction, unlike the HepG2 cell line commonly utilized for HCA studies. Furthermore, this study demonstrates that CYP3A4 induction can be quantified via a simple image analysis-based method, using HepaRG cells as a model system. Additionally, data demonstrate that the hepatocyte and biliary epithelial subpopulations characteristic of HepaRG cultures can be separated during analysis simply on the basis of nuclear size measurements. Proof of concept studies with fluorescent cell function reagents indicated that further multiparametric image-based assessment is achievable with HepaRG. In summary, image-based screening of metabolically competent human hepatocyte models cells such as HepaRG offers novel approaches for hepatotoxicity assessment and improved drug screening tools.
  • 11.

    【2hr】Proliferation and TH1/TH2 Cytokine Production in Human Peripheral Blood Mononuclear Cells after Treatment with Cypermethrin and Mancozeb In Vitro

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    机译 氯氰菊酯和Mancozeb体外处理后人外周血单个核细胞中增殖和TH1 / TH2细胞因子的产生
    摘要：In recent times, human cell-based assays are gaining attention in assessments of immunomodulatory effects of chemicals. In the study here, the possible effects of cypermethrin and mancozeb on lymphocyte proliferation and proinflammatory (tumor necrosis factor (TNF-) α) and immunoregulatory cytokine (interferon- (IFN-) γ, interleukins (IL) 2, 4, 6, and 10) formation in vitro were investigated. Human peripheral blood mononuclear cells (PBMC) were isolated and exposed for 6 hr to noncytotoxic doses (0.45–30 µM) of cypermethrin or mancozeb in the presence of activating rat S9 fraction. Cultures were then further incubated for 48 or 72 hr in fresh medium containing phytohemagglutinin (10 µg/mL) to assess, respectively, effects on cell proliferation (BrdU-ELISA method) and cytokine formation (flow cytometric bead immunoassays). Mancozeb induced dose-dependent increases in lymphocyte proliferation, inhibition of production of TNFα and the TH2 cytokines IL-6 and IL-10, and an increase in IFNγ (TH1 cytokine) production (at least 2-fold compared to control); mancozeb also induced inhibition of IL-4 (TH2) and stimulated IL-2 (TH1) production, albeit only in dose-related manners for each. In contrast, cypermethrin exposure did not cause significant effects on proliferation or cytokine profiles. Further studies are needed to better understand the functional significance of our in vitro findings.
  • 12.

    【2hr】Prognostic Factors in Acute Methadone Toxicity: A 5-Year Study

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    机译 美沙酮急性毒性的预后因素：5年研究
    摘要：Background. Delayed or recurrent profound respiratory depression, ventricular dysrhythmias, acute lung injury, and death are the major complications of MTD overdose. We aimed to clarify the prognostic factors in MTD toxicity. Materials and Methods. Retrospectively, medical files of all patients poisoned by MTD and older than 12 years of age who had presented to Loghman Hakim Poison Center between 2007 and 2012 were evaluated. The data was compared between survivors and nonsurvivors. Results. Twenty-eight out of 322 patients died (mortality rate = 8.7%). MTD-related death was higher in patients with acute on chronic toxicity who were on daily dose of MTD and had ingested higher doses (in comparison to those with acute toxicity due to first-time exposure; 13% versus 6%). Renal failure was the most common medical complication related to deaths due to MTD toxicity. Conclusions. Based on previous researches, the most common cause of MTD overdose-related deaths is respiratory impairment; however, in our study, acute renal failure with or without rhabdomyolysis was the main delayed cause of deaths in MTD-poisoned patients. Antidotal therapy, early recognition, and treatment of hemodynamic compromise and rhabdomyolysis can be life-saving in these patients.
  • 13.

    【2hr】Sanitary Risks Connected to the Consumption of Infusion from Senna rotundifolia L. Contaminated with Lead and Cadmium in Cotonou (Benin)

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    机译 与科托努（贝宁）的铅和镉污染的番泻叶番泻叶注射液消费有关的卫生风险
    摘要：This study carried out an assessment of sanitary risks connected to the consumption of Senna rotundifolia Linn. contaminated with lead and cadmium. This plant was collected and analyzed by atomic absorption spectrophotometry. The results revealed a contamination of plants from markets of Dantokpa, Vossa, and Godomey with heavy metals. Senna from Vossa was higher in cadmium and lead levels (Pb: 2.733 mg/kg ± 0.356 mg/kg; Cd: 0.58 mg/kg ± 0.044 mg/kg) compared to the two other places (Pb: 1.825 mg/kg ± 0.133 mg/kg, Cd: 0.062 mg/kg ± 0.015 mg/kg and Pb: 1.902 mg/kg ± 0.265 mg/kg, Cd: 0.328 mg/kg ± 0.024 mg/kg), respectively, for Dantokpa and Godomey. In terms of risk assessment through the consumption of Senna, the values recorded for lead were nine times higher with children and six times higher with adults than the daily permissive intake (Pb: 3.376 × 10−2 mg/kg/day for children and 2.105 × 10−2 mg/kg/day for adults versus 3.6 × 10−3 mg/kg/day for DPI). With respect to cadmium, there was no significant difference between the recorded values and the DPI (Cd: 1 × 14 10−3 mg/ kg/day for children and Cd: 0.71 × 10−3 mg/ kg/day for adults versus Cd: 1 × 10−3 mg/kg/day for adults). This exposure of the population to lead and cadmium through the consumption of antimalarial healing plants could pose public health problems.
  • 14.

    【2hr】Determination of Mercury Exposure among Dental Health Workers in Nakhon Si Thammarat Province, Thailand

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    机译 泰国洛坤府牙科保健工作者中汞暴露的测定
    摘要：Objectives. The main objective of this study was to assess the mercury exposure levels in dental health workers that work in dental clinics. The study evaluated the airborne and urinary mercury levels, the type of work done in the clinic, and the effect of mercury exposure on health of dental health workers. Material and Methods. A case-control study was conducted with 124 exposed and 124 matched nonexposed subjects. Personal and area samplings were conducted to quantify mercury concentrations by solid sorbent tube. Urine samples were collected to determine mercury levels by cold-vapor atomic absorption spectrometer mercury analyzer. Results and Discussion. 17.6% (n = 32/182) of the air samples were higher than the occupational exposure limit (OEL). A multiple regression model was constructed. Significant predictors of urinary mercury levels included dietary consumption (fish or seafood), duration of work (yrs), work position, personal protection equipment used (PPE), and personal hygiene behaviors. Significant correlations were observed between mercury levels in urine and mercury in storage areas (r = 0.499, P < 0.05) and between mercury levels in urine and airborne mercury in personal samplings (r = 0.878, P < 0.001). Conclusion. Improvements in working conditions, occupational health training, and PPE use are recommended to reduce mercury exposure.
  • 15.

    【2hr】Antigenotoxic Effect of Curcumin and Carvacrol against Parathion Induced DNA Damage in Cultured Human Peripheral Blood Lymphocytes and Its Relation to GSTM1 and GSTT1 Polymorphism

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    机译 姜黄素和香芹酚对硫磷对培养的人外周血淋巴细胞DNA损伤的抗毒作用及其与GSTM1和GSTT1多态性的关系
    摘要：In recent years, the use of organophosphorus pesticides has been extensively increased and these compounds signify a major class of agricultural pesticides today. We studied antigenotoxic potential of curcumin and carvacrol against the parathion induced DNA damage in cultured peripheral blood lymphocytes using sister chromatid exchanges as a biomarker of genotoxicity. Heparinised fresh blood from healthy individuals was treated with 2.5 μg/mL concentration of parathion in presence of curcumin and carvacrol in order to observe the antigenotoxic potential of both curcumin and carvacrol. Significant reduction (P < 0.05) was observed in the frequencies of SCEs in presence of 10 μg/mL and 15 μg/mL concentrations of curcumin as compared to parathion exposed sample. Similarly carvacrol had significant (P < 0.05) antigenotoxic effect at the concentrations of 2.5 μg/mL and 5.0 μg/mL against the parathion. We also studied the effect of GSTT1 and GSTM1 on genotoxicity of parathion and antigenotoxic potential of curcumin and carvacrol. We did not observe any significant effect (P > 0.05) of GSTT1 and GSTM1 polymorphism on genotoxicity of parathion and antigenotoxic potential of curcumin and carvacrol.
  • 16.

    【2hr】Anion Gap Toxicity in Alloxan Induced Type 2 Diabetic Rats Treated with Antidiabetic Noncytotoxic Bioactive Compounds of Ethanolic Extract of Moringa oleifera

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    机译 辣木乙醇提取物的抗糖尿病非细胞毒性生物活性化合物对四氧嘧啶诱导的2型糖尿病大鼠的阴离子间隙毒性
    摘要：Moringa oleifera (MO) is used for a number of therapeutic purposes. This raises the question of safety and possible toxicity. The objective of the study was to ascertain the safety and possible metabolic toxicity in comparison with metformin, a known drug associated with acidosis. Animals confirmed with diabetes were grouped into 2 groups. The control group only received oral dose of PBS while the test group was treated with ethanolic extract of MO orally twice daily for 5-6 days. Data showed that the extract significantly lowered glucose level to normal values and did not cause any significant cytotoxicity compared to the control group (P = 0.0698); there was no gain in weight between the MO treated and the control groups (P > 0.8115). However, data showed that treatment with an ethanolic extract of MO caused a decrease in bicarbonate (P < 0.0001), and more than twofold increase in anion gap (P < 0.0001); metformin treatment also decreased bicarbonate (P < 0.0001) and resulted in a threefold increase in anion gap (P < 0.0001). Conclusively, these data show that while MO appears to have antidiabetic and noncytotoxic properties, it is associated with statistically significant anion gap acidosis in alloxan induced type 2 diabetic rats.
  • 17.

    【2hr】Acute Toxicity and Determination of the Active Constituents of Aqueous Extract of Uncaria tomentosa Bark in Hyphessobrycon eques

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    机译 中华绒螯蟹马鞭毛树皮水提物的急性毒性及其有效成分的测定
    摘要：Uncaria tomentosa is a medicinal plant used in folk medicine by Amazon tribes. In this study the constituents of aqueous extract of U. tomentosa bark were quantified by chromatographic technique and its lethal concentration 50 (48 h) in Hyphessobrycon eques was determined. The chromatography showed high levels of oxindole alkaloids, quinovic acid glycosides, and low molecular weight polyphenols. The CL50 48 h was 1816 mg/L. Fish showed behavior changes at concentrations above 2000 mg/L, accompanied by a significant decrease of dissolved oxygen. At the highest concentration 100% mortality was observed attributed to oxygen reduction by the amount of oxindole alkaloids, polyphenols accumulation of the extract in the gills, and the interaction of these compounds with dopamine. In conclusion, the aqueous extract of U. tomentosa did not alter the chemical components and it was shown that U. tomentosa has low toxicity to H. eques; therefore, it can be used safely in this species.
  • 18.

    【2hr】Concentration of Cd, Pb, Hg, and Se in Different Parts of Human Breast Cancer Tissues

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    机译 人体乳腺癌组织不同部位的Cd，Pb，Hg和Se含量
    摘要：Breast cancer is the major cause of cancer morbidity and mortality between women in the world. Metals involved in environmental toxicology are closely related to tumor growth and cancer. On the other hand, some metals such as selenium have anticarcinogenic properties. The aim of this study is to determine the concentration of cadmium, lead, mercury, and selenium in separated parts of tegmen, tumor, tumor adiposity, and tegmen adiposity of 14 breast cancer tissues which have been analyzed by graphite furnace atomic absorption (AA-670) and ICP-OES (ULTIMA 2CE). Our results show that Se and Hg have maximum and minimum concentration, respectively. Statistical analysis reveals no significant differences between metal accumulations in different parts of cancer tissues (P > 0.05) and this observation might be due to the close relation of separated parts of fatty breast organ. Thus, we could conclude that a high level of these heavy metals is accumulated in Iranian cancerous breasts and their presence can be one of the reasons of cancer appearance.
  • 19.

    【2hr】Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

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    机译 西地那非可改善庆大霉素诱导的大鼠肾毒性：iNOS和eNOS的作用
    摘要：Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p.) for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production.
  • 20.

    【2hr】Xylazine as a Drug of Abuse and Its Effects on the Generation of Reactive Species and DNA Damage on Human Umbilical Vein Endothelial Cells

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    机译 赛拉嗪作为滥用药物及其对人脐静脉内皮细胞反应性物种产生和DNA损伤的影响
    摘要：Human xylazine (XYL) abuse among addicts has received great interest due to its potential toxic effects upon addicts and the need to understand the mechanism of action associated with the potential health effects. XYL is an alpha-2 agonist restricted to veterinarian applications, without human medical applications. Our previous work demonstrated that XYL and its combination with cocaine (COC) and/or 6-monoacetylmorphine (6-MAM) induce cell death through an apoptotic mechanism. The aim of this study was to determine the effect of xylazine on the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as well as DNA damage on endothelial cell. Human umbilical vein endothelial cells (HUVEC) were treated with XYL (60 μM), COC (160 μM), 6-MAM (160 μM), camptothecin (positive control, 50 μM), XYL/COC (50 μM), XYL/6-MAM (50 μM), and XYL/COC/6-MAM (40 μM) for a period of 24 hours. Generation of intracellular ROS, RNS, and DNA fragmentation were analyzed using a fluorometric assay. Results reveal that XYL and 6-MAM increase levels of ROS; no induction of RNS production was observed. The combination of these drugs shows significant increase in DNA fragmentation in G2/M phase, while XYL, COC, and 6-MAM, without combination, present higher DNA fragmentation in G0/G1 phase. These findings support that these drugs and their combination alter important biochemical events aligned with an apoptotic mechanism of action in HUVEC.
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