Радионуклиды и меченые соединения для биологии и медицины

There is growing concern regarding the health and safety issues of endocrine-disrupting chemicals (EDCs). Long-term exposure to EDCs has alarming adverse health effects through both hormone-direct and hormone-indirect pathways. Non-chemical agents, including physical agents such as artificial light, radiation, temperature, and stress exposure, are currently poorly investigated, even though they can seriously affect the endocrine system, by modulation of hormonal action. Several mechanisms have been suggested to explain the interference of EDCs with hormonal activity. However, difficulty in quantifying the exposure, low standardization of studies, and the presence of confounding factors do not allow the establishment of a causal relationship between endocrine disorders and exposure to specific toxic agents. In this review, we focus on recent findings on the effects of EDCs and hormone system modulators on the endocrine system, including the thyroid, parathyroid glands, adrenal steroidogenesis, beta-cell function, and male and female reproductive function.

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Impact of Chemical Endocrine Disruptors and Hormone Modulators on the Endocrine System

In recent years, the worldwide prevalence of overweight and obesity among adults and children has dramatically increased. The conventional model regarding the onset of obesity is based on an imbalance between energy intake and expenditure. However, other possible environmental factors involved, such as the exposure to chemicals like pesticides, cannot be discarded. These compounds could act as endocrine-disrupting chemicals (EDC) that may interfere with hormone activity related to several mechanisms involved in body weight control. The main objective of this study was to systematically review the data provided in the scientific literature for a possible association between prenatal and postnatal exposure to pesticides and obesity in offspring. A total of 25 human and 9 animal studies were analyzed. The prenatal, perinatal, and postnatal exposure to organophosphate, organochlorine, pyrethroid, neonicotinoid, and carbamate, as well as a combined pesticide exposure was reviewed. This systematic review reveals that the effects of pesticide exposure on body weight are mostly inconclusive, finding conflicting results in both humans and experimental animals. The outcomes reviewed are dependent on many factors, including dosage and route of administration, species, sex, and treatment duration. More research is needed to effectively evaluate the impact of the combined effects of different pesticides on human health.

Relationship between Prenatal or Postnatal Exposure to Pesticides and Obesity: A Systematic Review

Article history: Received May 04, 2020 Accepted June 07, 2020 Available online June 23, 2021 This study aimed to know the comparative histological structure and histochemistry of the Ileum in two birds that are the Turkey (Meleagris gallopavo) and the Cockatiel (Nymphicus hollandicus) using histological stains and histochemical techniques. The results showed that the Ileum wall in the two birds is composed of the histological layers that make up the rest of the gut wall, with many differences between them. The villi appeared in Turkey in various shapes, longer and more numerous than in the Cockatiel. The villi lined with a simple epithelial tissue in the two birds, containing the goblet cells. Lieberkuhkn's crypts under the villi appeared in the two birds and had spherical secretory, and some secretory units contained the enteroendocrine cells. The Muscularis Externa appeared distinctively in Turkey than in the Cockatiel, and it was of three sublayers while in the Cockatiel from two sublayers. Histochemical results showed medium to a strong positive response to the epithelial tissue to AB pH 1, AB pH 2.5, PAS techniques while a weak positive in the intestinal glands to these techniques, with varying degrees between the two birds. While the response was positive for BP technique in the epithelial tissue and negative in the glands, as well as the same response appeared for the SB technique. The current study concluded that the Ileum structure in the two birds is identical with histological and histochemical differences that are appropriate to the nature of each bird's food.

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Comparative histological and histochemical study of the ileum in two different birds

Key characteristics (KCs), properties of agents or exposures that confer potential hazard, have been developed for carcinogens and other toxicant classes. KCs have been used in the systematic assessment of hazards and to identify assay and data gaps that limit screening and risk assessment. Many of the mechanisms through which pharmaceuticals and occupational or environmental agents modulate immune function are well recognized. Thus KCs could be identified for immunoactive substances and applied to improve hazard assessment of immunodulatory agents.The goal was to generate a consensus-based synthesis of scientific evidence describing the KCs of agents known to cause immunotoxicity and potential applications, such as assays to measure the KCs.A committee of 18 experts with diverse specialties identified 10 KCs of immunotoxic agents, namely, 1) covalently binds to proteins to form novel antigens, 2) affects antigen processing and presentation, 3) alters immune cell signaling, 4) alters immune cell proliferation, 5) modifies cellular differentiation, 6) alters immune cell-cell communication, 7) alters effector function of specific cell types, 8) alters immune cell trafficking, 9) alters cell death processes, and 10) breaks down immune tolerance. The group considered how these KCs could influence immune processes and contribute to hypersensitivity, inappropriate enhancement, immunosuppression, or autoimmunity.KCs can be used to improve efforts to identify agents that cause immunotoxicity via one or more mechanisms, to develop better testing and biomarker approaches to evaluate immunotoxicity, and to enable a more comprehensive and mechanistic understanding of adverse effects of exposures on the immune system. https://doi.org/10.1289/EHP10800. 

Consensus on the Key Characteristics of Immunotoxic Agents as a Basis for Hazard Identification

Objective ― impact of different time regimens of deuterium depletion on progression of syngeneic grafted tumor in mice was investigated. Material and Methods ― Experiment was performed on 64 C57Bl/6 mice divided into two groups with substitution of regular water for deuterium depleted water: 30 days prior to tumor cell inoculation and sinse the 1st day of inoculation. Mice taking destilled mineralized water were considered as a control group. Half of the mice were injected melanoma B16 cells subcutaneously for assessment of survival rate and tumor growth inhibition index. The other mice were intravenously injected melanoma cells for estimation of lung hematogenous metastasis. Results ― Deuterium depletion began at the day of tumor inoculation did not change the parameters of survival rate (38.83±7.69 days vs. 41.33±6.22days in the control). Tumor growth inhibition was found only at initial stage of tumor progression. Number of melanoma lung metastasis did not differ from the control values (32.30±6.12 and 28.33±5.38. consequently). The group of mice with preliminary consumption of deuterium depleted water demonstrated significantly higher survival rate (70.10±16.20 days), tumor inhibition index, and attenuation of lung metastasis (6.0±1.20). Conclusion ― Our findings demonstrate that deuterium depletion exerts antitumor effect by both inhibition of tumor growth and metastasis, but development of the effect is time-dependent.

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Time-dependent effect of deuterium depletion on tumor growth and metastasis

Dichlorodiphenyltrichloroethane (DDT) is a persistent organic pollutant and one of the most widespread endocrine disrupting chemicals. The impact of low-dose exposure to DDT on the morphogenesis of the adrenal gland is still poorly understood. The development and function of zona glomerulosa in rats has been found to be associated with changes in the expression of the transcription factor Oct4 (Octamer 4), which is the most important player in cell pluripotency. The aim of the study was to investigate the morphogenesis and function of rat adrenal zona glomerulosa in rats exposed to low doses of DDT during prenatal and postnatal development and to determine the possible role of Oct4 in DDT-mediated structural and functional changes. The DDT-exposed rats demonstrated slower development and lower functional activity of the zona glomerulosa during the pubertal period associated with higher expression of Oct4. Further, accelerated growth and restoration of hormone production was associated with, firstly, a decrease in Oct4 expressing cells and secondly, the loss of the inverse relationship between basal aldosterone levels and the number of Oct4 expressing cells. Thus, the transcriptional factor Oct4 exhibited an altered pattern of expression in the DDT-exposed rats during postnatal development. The results of the study uncover a novel putative mechanism by which low doses of DDT disrupt the development of adrenal zona glomerulosa.

Impaired Morphogenesis and Function of Rat Adrenal Zona Glomerulosa by Developmental Low-Dose Exposure to DDT Is Associated with Altered Oct4 Expression.

Endocrine disruptors are exogenous compounds that pollute the environment and have effects similar to hormones when inside the body. One of the most widespread endocrine disruptors in the wild is the pesticide dichlorodiphenyltrichloroethane (DDT). Toxic doses of DDT are known to cause cell atrophy and degeneration in the adrenal zona fasciculata and zona reticularis. Daily exposure in a developing organism to supposedly non-toxic doses of DDT have been found to impair the morphogenesis of both the cortex and the medulla of the adrenal glands, as well as disturbing the secretion of hormones in cortical and chromaffin cells. Comparison of high and very low levels of DDT exposure revealed drastic differences in the morphological and functional changes in the adrenal cortex. Moreover, the three adrenocortical zones have different levels of sensitivity to the disruptive actions of DDT. The zona glomerulosa and zona reticularis demonstrate sensitivity to both high and very low levels of DDT in prenatal and postnatal periods. In contrast, the zona fasciculata is less damaged by low (supposedly non-toxic) exposure to DDT and its metabolites but is affected by toxic levels of exposure; thus, DDT exerts both toxic and disruptive effects on the adrenal glands, and sensitivity to these two types of action varies in adrenocortical zones. Disruptive low-dose exposure leads to more severe affection of the adrenal function.

Dichlorodiphenyltrichloroethane and the Adrenal Gland: From Toxicity to Endocrine Disruption

Objective ― The study is focused on the secretion of adrenal zona glomerulosa cells in rats exposed to low doses of dichlorodiphenyltrichloroethane (DDT) during prenatal and postnatal development. Material and Methods ― Experiment was carried out on male Wistar rats exposed to low dose of DDT during prenatal and postnatal development. Aldosterone serum levels, zona glomerulosa histology and fine structure of glomerulosa cells were examined in pubertal and adult rats. Results ― Rats exposed to low doses of DDT during prenatal and postnatal development showed lower aldosterone serum levels in puberty and restoration of aldosterone secretion after puberty. Histological examination revealed retardation of zona glomerulosa development and circulatory disorders in pubertal rats. Electron microscopy revealed typical signs of decreased steroidogenic activity of glomerulosa cells. After puberty DDT-exposed rats exhibited hyperplasia of zona glomerulosa and less pronounced changes in number and structure of mitochondria. Conclusion ― Developmental exposure to low doses of DDT resulted in dysmorphogenesis of zona glomerulosa and, therefore, in impaired aldosterone secretion in puberty. Restoration of normal secretion of aldosterone after puberty was achieved by hyperplasia of zona glomerulosa.

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Valentin V. Yaglov

Papers

Time-dependent effect of deuterium depletion on tumor growth and metastasis

Impaired Morphogenesis and Function of Rat Adrenal Zona Glomerulosa by Developmental Low-Dose Exposure to DDT Is Associated with Altered Oct4 Expression.

Dichlorodiphenyltrichloroethane and the Adrenal Gland: From Toxicity to Endocrine Disruption

Secretion of adrenal zona glomerulosa cells in rats exposed to low doses of dichlorodiphenyltrichloroethane during prenatal and postnatal development

Developmental exposure to low doses of dichlorodiphenyltrichloroethane impairs proliferative response of thymic lymphocytes to Concanavalin A in rats