Adv. Pharmacol. [JOURNAL]
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200 papers
Interactions between opioids and stimulants: Behavioral pharmacology of abuse-related effects.
Maguire DR, Minervini V
Adv Pharmacol · 2022 · PMID 35341563 · Publisher ↗
Opioid abuse continues to be a significant public health challenge, with rates of opioid-related overdose deaths increasing continuously over the last two decades. There also has been a sharp increase in overdose deaths...
Opioid abuse continues to be a significant public health challenge, with rates of opioid-related overdose deaths increasing continuously over the last two decades. There also has been a sharp increase in overdose deaths involving stimulant drugs, primarily cocaine and methamphetamine. Recent estimates indicate a high prevalence of co-use of opioids and stimulants, which is a particularly complex problem. Behavioral pharmacology research over the last few decades has characterized interactions between opioids and stimulants as well as evaluated potential treatments. This chapter describes interactions between opioids and stimulants, with a focus on pre-clinical studies of abuse-related behavioral effects using self-administration, reinstatement, drug discrimination, place conditioning, and intracranial self-stimulation paradigms in laboratory animals. In general, the literature provides substantial evidence of mutual enhancement between opioids and stimulants for abuse-related effects, although such results are not ubiquitous. Enhanced abuse-related effects could manifest in many ways including engaging in drug seeking and taking behaviors with greater persistence, effort, and motivation and/or increased likelihood of relapse. Moreover, studies on opioid/stimulant combinations set the stage for evaluating potential treatments for polysubstance use. Behavioral pharmacology research has proven invaluable for elucidating these relationships using rigorous experimental designs and quantitative analyses of pharmacological and behavioral data.
Endocrine disrupting chemicals: Understanding what matters.
Vandenberg LN, Turgeon JL
Adv Pharmacol · 2021 · PMID 34452698 · Publisher ↗
Abstract loading — click title to view on PubMed.
Epigenetics, estrogenic endocrine-disrupting chemicals (EDCs), and the brain.
Streifer M, Gore AC
Adv Pharmacol · 2021 · PMID 34452697 · Publisher ↗
Endocrine-disrupting chemicals (EDCs) are a major public health concern, yet there are gaps in knowledge about the mechanisms for their effects. The brain is incredibly sensitive to small changes in the hormonal environm...
Endocrine-disrupting chemicals (EDCs) are a major public health concern, yet there are gaps in knowledge about the mechanisms for their effects. The brain is incredibly sensitive to small changes in the hormonal environment during early development, with natural sex differences in gonadal hormones shaping the organization of sex-specific neural circuits early in life. EDC exposure during these periods can lead to lifelong impacts on neurobiological health outcomes. Recently, epigenetic mechanisms have been proposed as a potential molecular mechanism for effects of endogenous hormones on the organization of developing brain circuits, leading to speculation that these mechanisms may underlie the long-term impacts of EDC exposure. Of these mechanisms, DNA methylation, associated with gene suppression, and histone marks, associated with gene suppression or activation, will be discussed. We review the evidence for hormones and their role in brain sexual differentiation; underlying epigenetic mechanisms; and how two classes of estrogenic EDCs, BPA and PCBs, may interfere with these processes to change brain structure and function.
EDCs and male urogenital cancers.
Bornman MS, Aneck-Hahn NH
Adv Pharmacol · 2021 · PMID 34452696 · Publisher ↗
Male sex determination and sexual differentiation occur between 6-12 weeks of gestation. During the "male programming window" the fetal testes start to produce testosterone that initiates the development of the male repr...
Male sex determination and sexual differentiation occur between 6-12 weeks of gestation. During the "male programming window" the fetal testes start to produce testosterone that initiates the development of the male reproductive tract. Exposure to endocrine disrupting chemicals (EDCs) able to mimic or disrupt steroid hormone actions may disrupt testicular development and adversely impact reproductive health at birth, during puberty and adulthood. The testicular dysgenesis syndrome (TDS) occurs as a result inhibition of androgen action on fetal development preceding Sertoli and Leydig cell dysfunction and may result from direct or epigenetic effects. Hypospadias, cryptorchidism and poor semen quality are elements of TDS, which may be considered a risk factor for testicular germ cell cancer (TGCC). Exposure to estrogen or estrogenic EDCs results in developmental estrogenization/estrogen imprinting in the rodent for prostate cancer (PCa). This can disrupt prostate histology by disorganization of the epithelium, prostatic intraepithelial neoplasia (PIN) lesions, in particular high-grade PIN (HGPIN) lesions which are precursors of prostatic adenocarcinoma. These defects persist throughout the lifespan of the animal and later in life estrogen exposure predispose development of cancer. Exposure of pregnant dams to vinclozolin, a competitive anti-androgen, and results in prominent, focal regions of inflammation in all exposed animals. The inflammation closely resembles human nonbacterial prostatitis that occurs in young men and evidence indicates that inflammation plays a central role in the development of PCa. In conclusion, in utero exposure to endocrine disrupters may predispose to the development of TDS, testicular cancer (TCa) and PCa and are illustrations of Developmental Origins of Health and Disease (DOHaD).
Endocrine disrupting chemicals and breast cancer cells.
Darbre PD
Adv Pharmacol · 2021 · PMID 34452695 · Publisher ↗
Many hundreds of endocrine disrupting chemicals (EDCs) have been measured as entering human breast tissue from a range of environmental sources, and this review focuses on discussion of mechanisms by which such EDCs may...
Many hundreds of endocrine disrupting chemicals (EDCs) have been measured as entering human breast tissue from a range of environmental sources, and this review focuses on discussion of mechanisms by which such EDCs may be contributing to the globally rising incidence of breast cancer. Many of the distinguishing features of breast cancer may be accounted for by EDC exposure, including, but not limited to, the fact that many EDCs possess estrogenic activity and exposure to estrogen is a main risk factor for breast cancer. Studies of the actions of EDCs in human breast cancer cells are aided by use of the conceptual framework of the hallmarks of cancer, and, acting by a variety of genomic and nongenomic mechanisms, EDCs have now been shown to enable all the hallmarks of cancer to develop in human breast cancer cells. Many studies report that hallmarks can develop at concentrations which are within the range of those measured in human breast tissues, especially when added as mixtures. The varied levels of different EDCs measured in individual breast tissue samples together with the overlapping and complementary mechanisms of action of the EDCs imply that thematic mechanisms will be driven inevitably by different chemical mixtures. Despite the complexity, EDCs do need to now be acknowledged as a risk factor for breast cancer in order for preventative strategies to include reduction in EDC exposure.
The new kids on the block: Emerging obesogens.
Chamorro-Garcia R, Veiga-Lopez A
Adv Pharmacol · 2021 · PMID 34452694 · Full text
The current obesity epidemic is calling for action in the determination of contributing factors. Although social and life-style factors have been traditionally associated with metabolic disruption, a subset of endocrine-...
The current obesity epidemic is calling for action in the determination of contributing factors. Although social and life-style factors have been traditionally associated with metabolic disruption, a subset of endocrine-disrupting chemicals (EDCs), called obesogens are garnering increasing attention for their ability to promote adipose tissue differentiation and accumulation. For some chemicals, such as tributyltin, there is conclusive evidence regarding their ability to promote adipogenesis and their mechanism of action. In recent years, the list of chemicals that exert obesogenic potential is increasing. In this chapter, we review current knowledge of the most recent developments in the field of emerging obesogens with a specific focus on food additives, surfactants, and sunscreens, for which the mechanism of action remains unclear. We also review new evidence relative to the obesogenic potential of environmentally relevant chemical mixtures and point to potential therapeutic approaches to minimize the detrimental effects of obesogens. We conclude by discussing the available tools to investigate new obesogenic chemicals, strategies to maximize reproducibility in adipogenic studies, and future directions that will help propel the field forward.
Inappropriately sweet: Environmental endocrine-disrupting chemicals and the diabetes pandemic.
Schulz MC, Sargis RM
Adv Pharmacol · 2021 · PMID 34452693 · Full text
Afflicting hundreds of millions of individuals globally, diabetes mellitus is a chronic disorder of energy metabolism characterized by hyperglycemia and other metabolic derangements that result in significant individual...
Afflicting hundreds of millions of individuals globally, diabetes mellitus is a chronic disorder of energy metabolism characterized by hyperglycemia and other metabolic derangements that result in significant individual morbidity and mortality as well as substantial healthcare costs. Importantly, the impact of diabetes in the United States is not uniform across the population; rather, communities of color and those with low income are disproportionately affected. While excessive caloric intake, physical inactivity, and genetic susceptibility are undoubted contributors to diabetes risk, these factors alone fail to fully explain the rapid global rise in diabetes rates. Recently, environmental contaminants acting as endocrine-disrupting chemicals (EDCs) have been implicated in the pathogenesis of diabetes. Indeed, burgeoning data from cell-based, animal, population, and even clinical studies now indicate that a variety of structurally distinct EDCs of both natural and synthetic origin have the capacity to alter insulin secretion and action as well as global glucose homeostasis. This chapter reviews the evidence linking EDCs to diabetes risk across this spectrum of evidence. It is hoped that improving our understanding of the environmental drivers of diabetes development will illuminate novel individual-level and policy interventions to mitigate the impact of this devastating condition on vulnerable communities and the population at large.
Endocrine disrupting chemicals and thyroid hormone action.
Zoeller RT
Adv Pharmacol · 2021 · PMID 34452692 · Publisher ↗
Thyroid hormones (predominantly thyroxine, T4, and triiodothyronine, T3) are essential for normal development and for adult physiology. There are several challenges, however, that make identifying chemicals that produce...
Thyroid hormones (predominantly thyroxine, T4, and triiodothyronine, T3) are essential for normal development and for adult physiology. There are several challenges, however, that make identifying chemicals that produce adverse effects by interfering with the thyroid system difficult. First, individual variability in serum concentrations of thyroid hormones represent only about 10% of the population reference range that is considered to be "normal." This means that populations studies evaluating the relationship between chemical exposure and serum thyroid hormones must be large enough to overcome this internal variance. In addition, we know that there are chemicals that do not produce changes in thyroid hormone levels, but nevertheless impact thyroid signaling in target tissues. A good example is that of polychlorinated biphenyls (PCBs). PCB exposure during development are clearly associated with cognitive deficits in humans. But PCB exposure isn't uniformly associated with a reduction in serum thyroid hormone in human populations despite mechanistic studies showing that PCBs reduce serum T4 in animals. In contrast, perchlorate is a chemical that inhibits iodide uptake, thereby reducing thyroid hormone synthesis and serum hormone levels. Human studies have been variable in identifying a relationship between thyroid hormone and perchlorate exposure, but studies also show that dietary iodine, cigarette smoking and other factors can modify this relationship. The conclusion is that identifying chemicals that interfere with thyroid hormone could depend on in vitro analysis of chemicals that interact with different proteins important for thyroid hormone to function properly.
Toxicity testing and endocrine disrupting chemicals.
Vandenberg LN
Adv Pharmacol · 2021 · PMID 34452691 · Publisher ↗
Regulatory agencies around the world depend on standardized testing approaches to evaluate environmental chemicals for endocrine disrupting properties. The US Environmental Protection Agency (EPA) has developed a two-tie...
Regulatory agencies around the world depend on standardized testing approaches to evaluate environmental chemicals for endocrine disrupting properties. The US Environmental Protection Agency (EPA) has developed a two-tiered testing approach within its Endocrine Disruptor Screening Program (EDSP). The eleven Tier 1 and three Tier 2 EDSP assays can be used to identify chemicals that act as agonists or antagonists of estrogen receptor, androgen receptor, or thyroid hormone receptor, or chemicals that interfere with steroidogenesis. Additional assays have been developed in the context of Tox21, and others have been validated by the OECD. In spite of the availability of validated toxicity tests, problems have been identified with the approaches and methods used to identify endocrine disrupting chemicals (EDCs). This chapter will provide an overview of several of these issues including: (1) The way an EDC is defined by an agency impacts whether a specific test can be used to determine if a chemical is an EDC. This is especially important when considering which assays examine outcomes that are considered "adverse effects." (2) Some assumptions about the validated studies used to identify EDCs may not be true (e.g., their reproducibility has been questioned). (3) Many of the validated assays are less sensitive than other methods that have not yet been validated. Ultimately, these and other problems contribute to the current landscape, where testing approaches have failed to protect the public from known EDCs. The chapter concludes with a review of approaches that have been taken to improve current guideline studies.
Endocrine disrupting chemicals (EDCs) and placental function: Impact on fetal brain development.
Marinello WP, Patisaul HB
Adv Pharmacol · 2021 · PMID 34452690 · Publisher ↗
Pregnancy is a critical time of vulnerability for the development of the fetal brain. Exposure to environmental pollutants at any point in pregnancy can negatively impact many aspects of fetal development, especially the...
Pregnancy is a critical time of vulnerability for the development of the fetal brain. Exposure to environmental pollutants at any point in pregnancy can negatively impact many aspects of fetal development, especially the organization and differentiation of the brain. The placenta performs a variety of functions that can help protect the fetus and sustain brain development. However, disruption of any of these functions can have negative impacts on both the pregnancy outcome and fetal neurodevelopment. This review presents current understanding of how environmental exposures, specifically to endocrine disrupting chemicals (EDCs), interfere with placental function and, in turn, neurodevelopment. Some of the key differences in placental development between animal models are presented, as well as how placental functions such as serving as a xenobiotic barrier and exchange organ, immune interface, regulator of growth and fetal oxygenation, and a neuroendocrine organ, could be vulnerable to environmental exposure. This review illustrates the importance of the placenta as a modulator of fetal brain development and suggests critical unexplored areas and possible vulnerabilities to environmental exposure.
Impact of gestational exposure to endocrine disrupting chemicals on pregnancy and birth outcomes.
Padmanabhan V, Moeller J, Puttabyatappa M
Adv Pharmacol · 2021 · PMID 34452689 · Publisher ↗
With the advent of industrialization, humans are exposed to a wide range of environmental chemicals, many with endocrine disrupting potential. As successful maintenance of pregnancy and fetal development are under tight...
With the advent of industrialization, humans are exposed to a wide range of environmental chemicals, many with endocrine disrupting potential. As successful maintenance of pregnancy and fetal development are under tight hormonal control, the gestational exposure to environmental endocrine disrupting chemicals (EDC) have the potential to adversely affect the maternal milieu and support to the fetus, fetal developmental trajectory and birth outcomes. This chapter summarizes the impact of exposure to EDCs both individually and as mixtures during pregnancy, the immediate and long-term consequences of such exposures on the mother and fetus, the direct and indirect mechanisms through which they elicit their effects, factors that modify their action, and the research directions to focus future investigations.
Endocrine disrupting chemicals and the mammary gland.
Vandenberg LN
Adv Pharmacol · 2021 · PMID 34452688 · Publisher ↗
Development of the mammary gland requires coordination of hormone signaling pathways including those mediated by estrogen, progesterone, androgen and prolactin receptors. These hormones play important roles at several di...
Development of the mammary gland requires coordination of hormone signaling pathways including those mediated by estrogen, progesterone, androgen and prolactin receptors. These hormones play important roles at several distinct stages of life including embryonic/fetal development, puberty, pregnancy, lactation, and old age. This also makes the gland sensitive to perturbations from environmental agents including endocrine disrupting chemicals (EDCs). Although there is evidence from human populations of associations between EDCs and disruptions to breast development and lactation, these studies are often complicated by the timing of exposure assessments and the latency to develop breast diseases (e.g., years to decades). Rodents have been instrumental in providing insights-not only to the basic biology and endocrinology of the mammary gland, but to the effects of EDCs on this tissue at different stages of development. Studies, mostly but not exclusively, of estrogenic EDCs have shown that the mammary gland is a sensitive tissue, that exposures during perinatal development can produce abnormal mammary structures (e.g., alveolar buds, typically seen in pregnant females) in adulthood; that exposures during pregnancy can alter milk production; and that EDC exposures can enhance the response of the mammary tissue to hormones and chemical carcinogens. Other studies of persistent organic pollutants have shown that EDC exposures during critical windows of development can delay development of the gland, with lifelong consequences for the individual. Collectively, this work continues to support the conclusion that EDCs can harm the mammary gland, with effects that depend on the period of exposure and the period of evaluation.
Endocrine disrupting chemicals (EDCs) and sex steroid receptors.
Hall JM, Korach KS
Adv Pharmacol · 2021 · PMID 34452687 · Publisher ↗
Sex-steroid receptors (SSRs) are essential mediators of estrogen, progestin, and androgen signaling that are critical in vast aspects of human development and multi-organ homeostasis. Dysregulation of SSR function has be...
Sex-steroid receptors (SSRs) are essential mediators of estrogen, progestin, and androgen signaling that are critical in vast aspects of human development and multi-organ homeostasis. Dysregulation of SSR function has been implicated in numerous pathologies including cancers, obesity, Type II diabetes mellitus, neuroendocrine disorders, cardiovascular disease, hyperlipidemia, male and female infertility, and other reproductive disorders. Endocrine disrupting chemicals (EDCs) modulate SSR function in a wide variety of cell and tissues. There exists strong experimental, clinical, and epidemiological evidence that engagement of EDCs with SSRs may disrupt endogenous hormone signaling leading to physiological abnormalities that may manifest in disease. In this chapter, we discuss the molecular mechanisms by which EDCs interact with estrogen, progestin, and androgen receptors and alter SSR functions in target cells. In addition, the pathological consequences of disruption of SSR action in reproductive and other organs by EDCs is described with an emphasis on underlying mechanisms of receptors dysfunction.
Endocrine disrupting chemicals and reproductive disorders in women, men, and animal models.
Laws MJ, Neff AM, Brehm E … +2 more , Warner GR, Flaws JA
Adv Pharmacol · 2021 · PMID 34452686 · Full text
This chapter covers the known effects of endocrine disrupting chemicals (EDCs) on reproductive disorders. The EDCs represented are highly studied, including plasticizers (bisphenols and phthalates), chemicals in personal...
This chapter covers the known effects of endocrine disrupting chemicals (EDCs) on reproductive disorders. The EDCs represented are highly studied, including plasticizers (bisphenols and phthalates), chemicals in personal care products (parabens), persistent environmental contaminants (polychlorinated biphenyls), and chemicals in pesticides or herbicides. Both female and male reproductive disorders are reviewed in the chapter. Female disorders include infertility/subfertility, irregular reproductive cycles, early menopause, premature ovarian insufficiency, polycystic ovarian syndrome, endometriosis, and uterine fibroids. Male disorders include infertility/subfertility, cryptorchidism, and hypospadias. Findings from both human and animal studies are represented.
Endocrine disrupting chemicals (EDCs) and the neuroendocrine system: Beyond estrogen, androgen, and thyroid.
Patisaul HB
Adv Pharmacol · 2021 · PMID 34452685 · Publisher ↗
Hundreds of anthropogenic chemicals occupy our bodies, a situation that threatens the health of present and future generations. This chapter focuses on endocrine disrupting compounds (EDCs), both naturally occurring and...
Hundreds of anthropogenic chemicals occupy our bodies, a situation that threatens the health of present and future generations. This chapter focuses on endocrine disrupting compounds (EDCs), both naturally occurring and man-made, that affect the neuroendocrine system to adversely impact health, with an emphasis on reproductive and metabolic pathways. The neuroendocrine system is highly sexually dimorphic and essential for maintaining homeostasis and appropriately responding to the environment. Comprising both neural and endocrine components, the neuroendocrine system is hormone sensitive throughout life and touches every organ system in the body. The integrative nature of the neuroendocrine system means that EDCs can have multi-system effects. Additionally, because gonadal hormones are essential for the sex-specific organization of numerous neuroendocrine pathways, endocrine disruption of this programming can lead to permanent deficits. Included in this review is a brief history of the neuroendocrine disruption field and a thorough discussion of the most common and less well understood neuroendocrine disruption modes of action. Also provided are extensive examples of how EDCs are likely contributing to neuroendocrine disorders such as obesity, and evidence that they have the potential for multi-generational effects.
Endocrine disruptor global policy.
Kassotis CD, Trasande L
Adv Pharmacol · 2021 · PMID 34452684 · Publisher ↗
Over the past several decades, scientific consensus has grown around the concept and evidence for human health impacts from exposure to endocrine disrupting chemicals (EDCs). A series of publications have now demonstrate...
Over the past several decades, scientific consensus has grown around the concept and evidence for human health impacts from exposure to endocrine disrupting chemicals (EDCs). A series of publications have now demonstrated considerable economic costs of EDC exposure-induced adverse health outcomes. This research has suggested economic burdens in the hundreds of billions, even considering only a small subset of EDCs and health. As of yet, regulatory efforts and policies to protect and decrease human exposure to most EDCs have been insufficient and have not kept pace with the science. Given the overwhelming scientific evidence, referenced throughout this collection, as well as the economic costs of inaction, described here, regulations are clearly needed. The EU and some other countries have taken promising steps towards protective regulation of EDCs, though the response of the US and many other countries has been limited or altogether lacking. Regulatory bodies that have and continue to apply risk-based approaches to regulating EDCs have also failed to consider the complete economic impacts of EDC-related health impacts. In this chapter, we will discuss broad strategies taken to regulate EDCs, examine the approaches currently taken to regulate EDCs in a global context (discussing the strengths and weaknesses of these regulations), discuss the economic costs of EDC exposures (detailing where consideration of health and economic costs could improve regulations), and discuss next steps and novel approaches to adapting existing regulatory frameworks to this class of chemicals.
Preface.
Copple BL, Rockwell CE
Adv Pharmacol · 2021 · PMID 34099114 · Publisher ↗
Abstract loading — click title to view on PubMed.
The role of Nrf2 in autoimmunity and infectious disease: Therapeutic possibilities.
Freeborn RA, Rockwell CE
Adv Pharmacol · 2021 · PMID 34099113 · Publisher ↗
Nrf2 is a cytoprotective transcription factor which is involved in ameliorating oxidative stress and toxic insults. Recently, an immunomodulatory role for Nrf2 has gained appreciation as it has been shown to protect cell...
Nrf2 is a cytoprotective transcription factor which is involved in ameliorating oxidative stress and toxic insults. Recently, an immunomodulatory role for Nrf2 has gained appreciation as it has been shown to protect cells and hosts alike in a variety of immune and inflammatory disorders. However, Nrf2 utilizes numerous distinct pathways to elicit its immunomodulatory effects. In this review, we summarize the literature discussing the roles of Nrf2 in autoimmunity and infectious diseases with a goal of understanding the potential to therapeutically target Nrf2.
Nanomaterials to target immunity.
Manchanda R, Fernandez-Fernandez A, Paluri SLA … +1 more , Smith BR
Adv Pharmacol · 2021 · PMID 34099112 · Publisher ↗
Critical advances have recently been made in the field of immunotherapy, contributing to an improved understanding of how to harness and balance the power of immune responses in the treatment of diseases such as cancer,...
Critical advances have recently been made in the field of immunotherapy, contributing to an improved understanding of how to harness and balance the power of immune responses in the treatment of diseases such as cancer, cardiovascular disease, infectious diseases, and autoimmune diseases. Combining nanomedicine with immunotherapy provides the opportunity for customization, rational design, and targeting to minimize side effects and maximize efficacy. This review highlights current developments in the design and utilization of nano-based immunotherapy systems, including how rationally-designed nanosystems can target and modify immune cells to modulate immune responses in a therapeutic manner. We discuss the following topics: targeted immuno-engineered nanoformulations, commercial formulations, clinical applicability, challenges associated with current approaches, and future directions.
Neuroimmunology of depression.
Sarno E, Moeser AJ, Robison AJ
Adv Pharmacol · 2021 · PMID 34099111 · Full text
Depression is one of the leading causes of disability worldwide and a major contributor to the global burden of disease, yet the cellular and molecular etiology of depression remain largely unknown. Major Depressive Diso...
Depression is one of the leading causes of disability worldwide and a major contributor to the global burden of disease, yet the cellular and molecular etiology of depression remain largely unknown. Major Depressive Disorder (MDD) is associated with a variety of chronic physical inflammatory and autoimmune disorders, and mood disorders may act synergistically with other medical disorders to worsen patient outcomes. Here, we outline the neuroimmune complement, explore the evidence for altered immune system function in MDD, and present some of the potential mechanisms by which immune cells and molecules may drive the onset and course of MDD. These include pro-inflammatory signaling, alterations in the hypothalamic-pituitary-adrenal axis, dysregulation of the serotonergic and noradrenergic neurotransmitter systems, neuroinflammation, and meningeal immune dysfunction. Finally, we discuss the interactions between current antidepressants and the immune system and propose the possibility of immunomodulatory drugs as potential novel antidepressant treatments.
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