Pyrethroids and reproductive function: some endocrine disrupting perspectives from molecular simulations.

Pyrethroids are widely used insecticides with huge applications for household as well as agricultural purposes and contribute to improved product quality and higher yields. In recent decades, the demand for pyrethroids has increased significantly due to advantages such as broad-spectrum efficacy, high insecticidal potential, and lower pest resistance. However, several studies have suggested that human exposure to pyrethroids leads to reproductive problems.

Androgen receptor signaling and pyrethroids: Potential male infertility consequences.

Infertility is a global health concern inflicting a considerable burden on the global economy and a severe socio-psychological impact. Approximately 15% of couples suffer from infertility globally, with a male factor contribution of approximately 50%. However, male infertility remains largely unexplored, as the burden of infertility is mostly assigned to female people.

An Analysis of the Structural Relationship between Thyroid Hormone-Signaling Disruption and Polybrominated Diphenyl Ethers: Potential Implications for Male Infertility.

Polybrominated diphenyl ethers (PBDEs) are a common class of anthropogenic organobromine chemicals with fire-retardant properties and are extensively used in consumer products, such as electrical and electronic equipment, furniture, textiles, and foams. Due to their extensive use, PBDEs have wide eco-chemical dissemination and tend to bioaccumulate in wildlife and humans with many potential adverse health effects in humans, such as neurodevelopmental deficits, cancer, thyroid hormone disruption, dysfunction of reproductive system, and infertility. Many PBDEs have been listed as chemicals of international concern under the Stockholm Convention on Persistent Organic Pollutants.

Organotin Antifouling Compounds and Sex-Steroid Nuclear Receptor Perturbation: Some Structural Insights.

Organotin compounds (OTCs) are a commercially important group of organometallic compounds of tin used globally as polyvinyl chloride stabilizers and marine antifouling biocides. Worldwide use of OTCs has resulted in their ubiquitous presence in ecosystems across all the continents. OTCs have metabolic and endocrine disrupting effects in marine and terrestrial organisms.

Potential Disruption of Systemic Hormone Transport by Tobacco Alkaloids Using Computational Approaches.

Tobacco/nicotine is one of the most toxic and addictive substances and continues to pose a significant threat to global public health. The harmful effects of smoking/nicotine affect every system in the human body. Nicotine has been associated with effects on endocrine homeostasis in humans such as the imbalance of gonadal steroid hormones, adrenal corticosteroid hormones, and thyroid hormones.

Insights into the Endocrine Disrupting Activity of Emerging Non-Phthalate Alternate Plasticizers against Thyroid Hormone Receptor: A Structural Perspective.

Many endocrine-disrupting chemicals (EDCs) have a ubiquitous presence in our environment due to anthropogenic activity. These EDCs can disrupt hormone signaling in the human and animal body systems including the very important hypothalamic-pituitary-thyroid (HPT) axis causing adverse health effects. Thyroxine (T4) and triiodothyronine (T3) are hormones of the HPT axis which are essential for regulation of metabolism, heart rate, body temperature, growth, development, etc.

Hemodynamic, endocrine, and gene expression mechanisms regulating equine ovarian follicular and cellular development.

Ovulatory follicle development and associated oocyte maturation involve complex coordinated molecular and cellular mechanisms not yet fully understood. This study addresses the relationships among follicle diameter, follicle wall blood flow, follicular-fluid factors, and gene expression for follicle growth, steroidogenesis, angiogenesis, and apoptosis in granulosa/cumulus cells and oocytes during different stages from the beginning of largest/ovulatory follicle to impending ovulation in mares. The most remarkable findings were (i) a positive association between follicle development, follicle blood flow, intrafollicular follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and messenger RNA (mRNA) expression for FSHR and LHCGR in granulosa cells of the largest/ovulatory follicle; (ii) a plateau or decrease in follicle diameter and blood flow and granulosa cell mRNA for FSHR, LHCGR, IGF1R, VEGFR2, CYP19A1, and CASP3 at the preovulatory stage; (iii) higher StAR and BCL2 and lower CASP3 mRNA in granulosa cells at the time of impending ovulation; (iv) greater IGF1R mRNA for granulosa cells at the predeviation stage; and (v) lower FSHR, LHCGR, IGF1R, and VEGFR2 mRNA in cumulus cells and greater LHCGR and IGF1R mRNA in oocytes at the ovulatory stage.

Structural binding perspectives of common plasticizers and a flame retardant, BDE-153, against thyroxine-binding globulin: potential for endocrine disruption.

The human exposure to diverse endocrine-disrupting chemicals (EDCs) has increased dramatically over several decades with very adverse health effects. Plasticizers and flame retardants constitute important classes of EDCs interfering in endocrine physiology including the thyroid function. Thyroxine (T4) is an important hormone regulating metabolism and playing key roles in developmental processes.

Structural Aspects of Potential Endocrine-Disrupting Activity of Stereoisomers for a Common Pesticide Permethrin against Androgen Receptor.

Endocrine-disrupting chemicals (EDCs) are a serious global public health and environmental concern. Pyrethroids are insecticide chemicals that are extensively used for crop protection and household purposes but have been identified as EDCs. On account of their ubiquitous environmental presence, human exposure occurs via food, dermal, or inhalation routes and is associated with health problems, including reproductive dysfunction.

Endocrine Disruption: Structural Interactions of Androgen Receptor against Di(2-ethylhexyl) Phthalate and Its Metabolites.

Diethylhexyl phthalate (DEHP) is a commonly used plasticizer in the manufacture of polyvinyl chloride plastics for household and commercial use. DEHP is a ubiquitous ecocontaminant and causes developmental and reproductive problems in children and adults. After exposure, DEHP is metabolized by endogenous hydrolysis and oxidation into the primary metabolite, mono-(2-ethylhexyl) phthalate (MEHP), and the secondary metabolites, mono-(2-ethyl-5-hydroxhexyl)phthalate (5-OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5-oxo-MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (5-cx-MEPP), and mono-[(2-carboxymethyl)hexyl] phthalate (2-cx-MMHP).

Structural studies on the endocrine-disrupting role of polybrominated diphenyl ethers (PBDEs) in thyroid diseases.

Polybrominated diphenyl ethers (PBDEs) are synthetic brominated flame retardants with extensive applications in daily-life consumer products. However, PBDEs have become ubiquitous environmental contaminants due to their leach-out capability. The hazardous human health effects and endocrine-disrupting activity of PBDEs have led many governmental organizations to impose ban on their manufacture, causing their gradual phase out from commercial products.

Endocrine disruption: Molecular interactions of environmental bisphenol contaminants with thyroid hormone receptor and thyroxine-binding globulin.

Many bisphenol A (BPA) analogs have been commercially used recently, such as 2,2-bis(4-hydroxyphenyl)butane (BPB), 4,4'-ethylidenebisphenol, 4,4'-methylenediphenol (BPF), 4,4'-(1,4-phenylenediisopropylidene)bisphenol (BPP), 4,4'-dihydroxydiphenyl sulfone (BPS), 4,4'-cyclohexylidenebisphenol (BPZ), 4,4'-(hexafluoroisopropylidene)diphenol (BPAF), 4,4'-(1-phenylethylidene)bisphenol (BPAP), and 2,2-bis(4-hydroxy-3,5-dimethylphenyl)propane (TMBPA), to circumvent adverse effects of BPA. However, their increasing use is also contaminating the environment, which is a potential cause of concern for human health. Thyroid hormone transport and signaling are potential targets for endocrine-disrupting activity of BPA analogs.

Structural binding perspectives of a major tobacco alkaloid, nicotine, and its metabolite cotinine with sex-steroid nuclear receptors.

Globally, more than a billion people smoke tobacco making it one of the biggest public health problems and a leading risk factor for global deaths. Nicotine, the main alkaloid in tobacco, has been shown to be associated with fertility problems in men and women. The adverse effects of tobacco/nicotine on reproduction have been attributed to deleterious effects on gametes, steroidogenic imbalance, and competitive inhibition of steroid receptors.

Structural binding interactions of tetrabromobisphenol A with sex steroid nuclear receptors and sex hormone-binding globulin.

Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant owing to its efficient fire-breaking property. However, leaching of TBBPA into the environment has been a global health concern due to the endocrine-disrupting activity (EDA) associated with TBBPA exposure. Limited studies are available on the hazardous effects of TBBPA on reproductive function.

Genetic investigations on causes of male infertility in Western Saudi Arabia.

In recent years, genetic studies have yielded great progress in elucidating causes of male infertility. This investigation aims to identify frequent genetic abnormalities, that is, sex chromosome aneuploidies and Y-chromosome microdeletions among infertile men in Western Saudi Arabia. From a population of infertile patients, 88 male patients with either azoospermia or severe oligozoospermia (sperm concentration <5 million/ml) were selected.

Structural characterization of potential endocrine disrupting activity of alternate plasticizers di-(2-ethylhexyl) adipate (DEHA), acetyl tributyl citrate (ATBC) and 2,2,4-trimethyl 1,3-pentanediol diisobutyrate (TPIB) with human sex hormone-binding globulin.

Plasticizers are chemical compounds used to increase the softness and fluidity of polymer materials. Phthalate compounds constitute the most common class of compounds used as plasticizers. However, phthalate plasticizers, especially the predominant di(2-ethylhexyl)phthalate, have been shown to have adverse effects on environment and human health.

Lactoperoxidase immobilization on silver nanoparticles enhances its antimicrobial activity.

Lactoperoxidase (LPO) is an antimicrobial protein present in milk that plays an important role in natural defence mechanisms during neonatal and adult life. The antimicrobial activity of LPO has been commercially adapted for increasing the shelf life of dairy products. Immobilization of LPO on silver nanoparticles (AgNPs) is a promising way to enhance the antimicrobial activity of LPO.

Structural studies on inhibitory mechanisms of antibiotic, corticosteroid and catecholamine molecules on lactoperoxidase.

Aim: Lactoperoxidase (LPO) is an essential protein with broad spectrum antimicrobial activity present in mammalian milk. It imparts immunity to infants against wide range of pathogenic infections. Several in vitro studies have shown inhibition of LPO activity by pharmaceutical compounds including commonly used antibiotics such as ampicillin and gentamicin, and molecules like prednisolone, norepinephrine, etc.

In silico identification of genes involved in chronic metabolic acidosis.

Aims: Chronic metabolic acidosis (CMA) refers to increased plasma acidity due to disturbed acid-base equilibrium in human body. CMA leads to many dysfunctions including disorders of intestinal metabolism and barrier functions. The human body responds to these intestinal dysfunctions by creating a compensatory mechanism at genomic level in intestinal epithelial cells.

Lactoperoxidase, an Antimicrobial Milk Protein, as a Potential Activator of Carcinogenic Heterocyclic Amines in Breast Cancer.

Background: Lactoperoxidase (LPO) is an antimicrobial protein secreted from mammary, salivary and other mucosal glands. It is an important member of heme peroxidase enzymes and the primary peroxidase enzyme present in breast tissues. In addition to the antimicrobial properties, LPO has been shown to be associated with breast cancer etiology.

Molecular Interactions of Carcinogenic Aromatic Amines, 4-Aminobiphenyl and 4,4'-Diaminobiphenyl, with Lactoperoxidase - Insight to Breast Cancer.

Background/aim: Lactoperoxidase (LPO) is an antimicrobial protein present in milk, saliva, gastric secretions, tears and upper respiratory tract secretions. LPO constitutes an important enzyme of the human immune defense system. However, LPO has also been suggested to be involved in breast cancer etiology through production of reactive free radicals and activation of carcinogenic aromatic compounds.

Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin.

Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties.

Comparative study of fatty-acid composition of table eggs from the Jeddah food market and effect of value addition in omega-3 bio-fortified eggs.

Health consciousness has increased the desire of people around the world to consume functional foods. Omega-3 essential fatty acids are one among these beneficial and important health supplements without which a general predisposition to degenerative and stress related disorders can occur. Saudi Arabia has shown an alarming increase in obesity (Al-Nozha et al.

Possible Molecular Interactions of Bexarotene - A Retinoid Drug and Alzheimer's Aβ Peptide: A Docking Study.

Background: Alzheimer's disease (AD) pathogenesis is primarily hallmarked by the production and accumulation of amyloid beta (Aβ) peptide. Along with the understanding of the neurodegenerative disease progression and its pathophysiological mechanisms, development of anti-Aβ targeted effective therapeutics is essential for AD management. Numerous therapeutic approaches targeting the production, toxicity and removal of Aβ are being attempted worldwide.

Peroxisome Proliferator-activated Receptors as Potential Targets for Carcinogenic Activity of Polychlorinated Biphenyls: A Computational Perspective.

Background: Polychlorinated biphenyls (PCBs) are ubiquitous environment-contaminating synthetic chemicals that have been associated with increased risk of hepatic cancer, melanoma, non-Hodgkin lymphoma and cancer of many other body organs. Structural binding analyses of PCB 77 and PCB 118 with peroxisome proliferator-activated receptors (PPARα, PPARβ/δ and PPARγ) was performed to predict the association of PCBs with potential disruption of PPAR signaling pathways.

Materials And Methods: The crystal structures of human PPARα, PPARβ/δ and PPARγ were obtained from the Protein Data Bank.