Estrogen receptor α polymorphism is associated with dementia in a Brazilian cohort.

The growth of the elderly population is a worldwide phenomenon and it is associated with chronic diseases, including dementia. In this scenario, the present study aimed to evaluate a possible association of estrogen receptor α polymorphisms with dementia in a Brazilian cohort. The subject sample was divided into two groups, control (n = 105) and case (n = 73), according to analysis of two predictive dementia tests (MMSE and CDR). The genotyping for the ERα PvuII (c.454-397T>C, rs2234693) and XbaI (c.454-351A>G, rs9340799) polymorphisms were performed by polymerase chain reaction-restriction fragment length polymorphism. The ERα PvuII pp genotype was associated with higher odds ratio for dementia (OR = 3.42, 95% CI = 1.33-8.77, p = 0.01, in a model including covariates. A linear regression model identified significant associations of the ERα PvuII genotypes (independent variable) with CDR scale (dependent variable), ß = 0.26 and p = 0.001. In conclusion, estrogen receptor α PvuII polymorphism is associated with dementia in a Brazilian cohort. This finding may be useful for the identification of a possible set of significant genetic and clinical biomarkers for better understanding pathophysiology, early diagnosis and management of dementia.

Overview of the Pathophysiological Implications of Organotins on the Endocrine System.

Organotins (OTs) are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic-pituitary axis), altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus) or peripheral (e.g., adipose tissue) mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed.

Organotin Exposure and Vertebrate Reproduction: A Review.

Organotin (OTs) compounds are organometallic compounds that are widely used in industry, such as in the manufacture of plastics, pesticides, paints, and others. OTs are released into the environment by anthropogenic actions, leading to contact with aquatic and terrestrial organisms that occur in animal feeding. Although OTs are degraded environmentally, reports have shown the effects of this contamination over the years because it can affect organisms of different trophic levels. OTs act as endocrine-disrupting chemicals (EDCs), which can lead to several abnormalities in organisms. In male animals, OTs decrease the weights of the testis and epididymis and reduce the spermatid count, among other dysfunctions. In female animals, OTs alter the weights of the ovaries and uteri and induce damage to the ovaries. In addition, OTs prevent fetal implantation and reduce mammalian pregnancy rates. OTs cross the placental barrier and accumulate in the placental and fetal tissues. Exposure to OTs in utero leads to the accumulation of lipid droplets in the Sertoli cells and gonocytes of male offspring in addition to inducing early puberty in females. In both genders, this damage is associated with the imbalance of sex hormones and the modulation of the hypothalamic-pituitary-gonadal axis. Here, we report that OTs act as reproductive disruptors in vertebrate studies; among the compounds are tetrabutyltin, tributyltin chloride, tributyltin acetate, triphenyltin chloride, triphenyltin hydroxide, dibutyltin chloride, dibutyltin dichloride, diphenyltin dichloride, monobutyltin, and azocyclotin.

The Pollutant Organotins Leads to Respiratory Disease by Inflammation: A Mini-Review.

Organotins (OTs) are organometallic pollutants. The OTs are organometallic pollutants that are used in many industrial, agricultural, and domestic products, and it works as powerful biocidal compound against large types of microorganisms such as fungi and bacteria. In addition, OTs are well known to be endocrine-disrupting chemicals, leading abnormalities an "imposex" phenomenon in the female mollusks. There are some studies showing that OTs' exposure is responsible for neural, endocrine, and reproductive dysfunctions in vitro and in vivo models. However, OTs' effects over the mammalian immune system are poorly understood, particularly in respiratory diseases. The immune system, as well as their cellular components, performs a pivotal role in the control of the several physiologic functions, and in the maintenance and recovery of homeostasis. Thus, it is becoming important to better understand the association between environmental contaminants, as OTs, and the physiological function of immune system. There are no many scientific works studying the relationship between OTs and respiratory disease, especially about immune system activation. Herein, we reported studies in animal, humans, and in vitro models. We searched studies in PUBMED, LILACS, and Scielo platforms. Studies have reported that OTs exposure was able to suppress T helper 1 (Th1) and exacerbate T helper 2 (Th2) response in the immune system. In addition, OTs' contact could elevate in the airway inflammatory response, throughout a mechanism associated with the apoptosis of T-regulatory cells and increased oxidative stress response. In addition, OTs induce macrophage recruitment to the tissue, leading to the increased necrosis, which stimulates an inflammatory cytokines secretion exacerbating the local inflammation and tissue function loss. Thus, the main intention of this mini-review is to up to date the main findings involving the inflammatory profile (especially Th1 and Th2 response) in the respiratory tract as a result of OTs' exposure.