Photocatalytic mechanisms of indoleamine destruction by the quinalphos metabolite 2-hydroxyquinoxaline: a study on melatonin and its precursors serotonin and N-acetylserotonin

The redox-active quinalphos main metabolite, 2-hydroxyquinoxaline, is particularly effective under excitation by light. We have studied the photocatalytic destruction of melatonin and its precursors, because the cytoprotective indoleamine has been detected in high quantities in mammalian skin. In photooxidation reactions, in which melatonin, N-acetylserotonin and serotonin are destroyed by 2-hydroxyquinoxaline, the photocatalyst is virtually not consumed. Rates of melatonin and serotonin destruction are not changed by the singlet oxygen quencher 1,4-diazabicyclo-(2,2,2)-octane, indicating that this oxygen species is not involved in the primary reactions, so that the persistence of 2-hydroxyquinoxaline has to be explained by redox cycling. This should imply formation of an organic radical, presumably the quinoxaline-2-oxyl radical, from which 2-hydroxyquinoxaline is regenerated by electron abstraction from indolic radical scavengers. Electron donation by 2-hydroxyquinoxaline is demonstrated by reduction of the 2,2′-azino-bis-(3-ethylbenzthiazolinyl-6-sulfonic acid) cation radical under ultrasound excitation. The compound 2-hydroxyquinoxaline interacts with the specific superoxide anion scavenger Tiron. Formation of oligomeric products from melatonin and serotonin is strongly inhibited by sodium dithionite. Products from photocatalytic indolamine conversion are predominantly dimers and oligomers. No kynuramines were detected in the case of serotonin oxidation, and melatonin's otherwise prevailing oxidation product N ¹-acetyl-N ²-formyl-5-methoxykynuramine, another cytoprotective metabolite, is only formed in relatively small quantities. The proportion between products from melatonin is changed by 1,4-diazabicyclo-(2,2,2)-octane: singlet oxygen, also formed under the influence of excited 2-hydroxyquinoxaline, only affects secondary reactions.     

Biochemical alterations in rat brain following aluminum exposure: Protection with centrophenoxine

Aluminum (Al) is a neurotoxicant potentially affecting ionic, cholinergic, and dopaminergic neurotransmission in the central nervous system. These alterations are known to be associated with learning ability, adaptive responses, and other aspects of behavior. The present experiment was designed to study the neurotoxic consequences of Al exposure on neurotransmitters like dopamine (DA), serotonin (5-HT), norepinephrine (NE) along with the activity of acetylcholinesterase (AChE). Furthermore, Centrophenoxine (CpH) was administered as a post treatment to evaluate its potential in Al-induced neurotoxicity. The cognitive functions and memory loss were also studied after both Al and CpH administration. Al was administered orally at a dose of 40?mg?kg^?1?day^?1 for a period of 8 weeks, whereas CpH was administered intraperitoneally at a dose of 100^?1?mg?kg^?1?day^?1 for a period of 6 weeks. The study was carried out in four regions of the brain, namely cerebrum, cerebellum, medulla oblongata, and hypothalamus. A significant reduction in AChE activity and different neurotransmitters was observed after Al exposure in the regions. CpH as a post treatment proved beneficial in restoring these alterations. Al exposure also affected the cognitive functions and short-term memory, which were significantly improved following CpH post treatment.     

2,4-二叔丁基苯酚对斑马鱼早期发育阶段的神经毒性

2,4-二叔丁基苯酚（2,4-di-tert-butylphenol,2,4-DTBP）作为一种合成酚类抗氧化剂（Synthetic Phenolic Antioxidants,SPAs）被广泛应用于塑料、橡胶、食品等工业产品中,近年来在水体、空气、生物体中被不同程度检出.然而目前有关2,4-DTBP的毒理学研究十分有限,尤其是对鱼类早期发育阶段的神经毒性效应尚未可知.因此,本文以斑马鱼为研究对象,在涵盖环境相关浓度水平上（0.01、0.1和1 μmol·L^-1,即2.06、20.6和206 μg·L^-1）,从运动活性、焦虑行为及多巴胺和5-羟色胺神经信号通路的基因转录水平探讨2,4-DTBP对斑马鱼早期发育阶段的神经毒性效应及其作用机制.结果发现,0.01和0.1 μmol·L^-1 2,4-DTBP暴露引起仔鱼在暗周期过度活跃,1 μmol·L^-1 2,4-DTBP暴露引起仔鱼在光周期异常平静及焦虑行为,斑马鱼的行为异常可能与5ht1ab 和drd1的过度表达有关.研究表明,2,4-DTBP可能对斑马鱼早期发育阶段具有神经毒性,且不同剂量下的作用机制不同.     

Effect of the appetite stimulant cyproheptadine on deoxynivalenol ‐ induced reductions in feed consumption and weight gain in the mouse 1

Abstract

Deoxynivalenol (DON, vomitoxin), a Fusarium mycotoxin, is suspected of inducing its anorectic/feed refusal activity through a serotoninergic (5HT) mechanism, possible via 5HT₂‐receptors. In this study the efficiency of cyproheptadine (CYP), a serotonin antagonist and known appetite stimulant, to attenuate the adverse effect of DON was investigated in mice. CYP was administered in the feed for two days before animals began receiving the DON, which was also added to the feed. Both agents were administered concurrently thereafter for a 12‐day period. Dosing levels included various combinations of the two compounds, ranging from 0–16 ppm DON and 0–20 ppm CYP.

Results showed that CYP could effectively offset the reduction in feed intake caused by dietary DON, but only when dose levels were optimized (CYP appeared to have a narrow effective dose range, which was also dependent on the DON concentration). In fact, optimum CYP doses were able to enhance feed intake in DON‐fed mice above control levels, indicating that more than just a direct block of the toxin's effect was occurring. Conversely though, the effect of CYP on weight gain (WG) was ambiguous. At the lower CYP doses (≤ 5 ppm), alone or in combination with the lowest DON level tested (4 ppm), a modest positive effect was noted, but at the higher DON concentrations (≥ 8 ppm) the overall WG generally remained depressed, and tended to be reduced further by increasing doses of CYP.

These results provide additional support that serotoninergic mechanisms probably play a role in mediating DON‐induced reduction in feed intake. Where and how DON actually initiates its anorectic effect, however, has not been resolved.     

抗抑郁药物舍曲林和氟西汀在实验室构建的三层水生食物链中的生物积累和营养动力学研究

目前关于药物在水生生物中富集的报道越来越多,但人们对它们在水生食物网中的营养转移却知之甚少。选择了2种在水环境中经常被监测到的选择性5-羟色胺再摄取抑制剂(SSRIs),本文在实验室可控条件下,通过构建水生链的SSRIs暴露试验,研究了舍曲林和氟西汀的生物积累和营养动力学。在2个3层食物链中(Acer platanoides,是 Asellus aquaticus的食物,而相应地 Asellus aquaticus是Notonecta glauca 或 Pungitius pungitius的食物),随着营养级的递增,这2种可离子化的、弱碱药物均显示出较低的生物积累因子(BAFs)(这表明没有生物放大)。A. platanoides、A. aquaticus、N. glauca和P. pungitius体内的舍曲林的平均BAFs分别为2200 L/kg、360 L/kg、26 L/kg和49 L/kg,氟西汀的平均BAFs分别为1300 L/kg、110 L/kg、11 L/kg和41 L/kg。生物积累因子(BAFs)的测量值等于或低于生物富集因子(BCFs)的测量值,这进一步证明了饮食的微弱影响。生物脂含量与BAFs没有正相关性,这表明其他的过程在驱动SSRI生物累积的种间差异。这里将经验参数值带入一个生物累积模型中计算,发现模拟与经验BAFs(预测r²=-0.63)之间相关性较差。综上所述,这些可离子化的药物明显缺乏生物放大作用,环境问题不应只关注较高的营养水平,而应关注在任何营养水平上有高BCFs的物种。
精选自Bostr?m, M. L., Ugge, G., J?nsson, J. ?. and Berglund, O. (2017), Bioaccumulation and trophodynamics of the antidepressants sertraline and fluoxetine in laboratory-constructed, 3-level aquatic food chains. Environmental Toxicology and Chemistry, 36: 1029–1037. doi: 10.1002/etc.3637
详情请见http://onlinelibrary.wiley.com/doi/10.1002/etc.3637/full
     

Epidemiology of centipede exposures reported to Texas poison control centers, 1998–2004

Centipedes are found globally, including the southern United States. Although centipede bites may cause pain, the bite is generally not considered life threatening. The present retrospective investigation studied the epidemiology of centipede exposures reported to Texas poison control centers. Cases were all human exposures reported during 1998–2004 that involved centipedes. There were totally 851 cases. Among the cases with a known patient age, 16% were less than 6 years of age, 19% were 6–19, and 65% were greater than 19 years. Females accounted for 55% of the patients with known gender. The reported centipede exposures were managed on site (outside of a health care facility) in 93% of the cases. Of the 305 cases with a known clinical outcome, 82% had minor effects. Cases exhibited a seasonal trend, with most of the reports occurring during July–September. There was no clear geographic pattern to the reported centipede exposures, although the highest rate occurred in West Texas. Dermal irritation or pain was reported in 73% of cases and the treatment by decontamination via irrigation was reported for 76% of the cases during 2000–2004.