Biological effects of vanillic acid, iso-vanillic acid, and orto-vanillic acid as environmental pollutants.

Vanillic acid (4-hydroxy-3-methoxybenzoic acid) (VA) is a natural benzoic acid derivative commonly found in herbs, rice, maize, and some fruits and vegetables. However, due to the wide use of VA in various industrial sectors, its presence in the environment might harm living organisms. This study evaluated the toxicity of VA and its isomers, iso-VA and orto-VA. Firstly, the antimicrobial effect of VA and its isomers iso-VA and orto-VA (in doses of 1000; 100, 10, 1; 0.1; 0.01 mg/L) against Escherichia coli, Sarcina spp., Enterobacter homaechei, Staphylococcus aureus and Candida albicans were identified. The toxic effect and protein degradation potential of VA and its isomers were determined using E. coli grpE:luxCDABE and lac:luxCDABE biosensor strains. However, the genotoxicity and oxidative stress generation were assessed with the E. coli recA:luxCDABE biosensor and E. coli strain. The results showed that VA, iso-VA, and orto-VA exhibited antimicrobial activity against all tested bacterial strains. However, VA's antimicrobial effect differed from iso-VA and orto-VA. Similar toxic, genotoxic, and oxidative stress-inducing effects were observed for VA and its isomers. Each compound exhibited toxicity, cellular protein degradation, and genotoxic activity against E. coli grpE:luxCDABE, E. coli lac:luxCDABE, and E. coli recA:luxCDABE strains. Analysis of reactive oxygen species (ROS) generation within E. coli cells highlighted oxidative stress as a contributing factor to the toxicity and genotoxicity of VA and its isomers. While the findings suggest potential applications of VA compounds as food preservatives, their presence in the environment raises concerns regarding the risks posed to living organisms due to their toxic and genotoxic characteristics.

Re-establishing the comprehension of phytomedicine and nanomedicine in inflammation-mediated cancer signaling.

Recent mounting evidence has revealed extensive genetic heterogeneity within tumors that drive phenotypic variation affecting key cancer pathways, making cancer treatment extremely challenging. Diverse cancer types display resistance to treatment and show patterns of relapse following therapy. Therefore, efforts are required to address tumor heterogeneity by developing a broad-spectrum therapeutic approach that combines targeted therapies. Inflammation has been progressively documented as a vital factor in tumor advancement and has consequences in epigenetic variations that support tumor instigation, encouraging all the tumorigenesis phases. Increased DNA damage, disrupted DNA repair mechanisms, cellular proliferation, apoptosis, angiogenesis, and its incursion are a few pro-cancerous outcomes of chronic inflammation. A clear understanding of the cellular and molecular signaling mechanisms of tumor-endorsing inflammation is necessary for further expansion of anti-cancer therapeutics targeting the crosstalk between tumor development and inflammatory processes. Multiple inflammatory signaling pathways, such as the NF-κB signaling pathway, JAK-STAT signaling pathway, MAPK signaling, PI3K/AKT/mTOR signaling, Wnt signaling cascade, and TGF-ß/Smad signaling, have been found to regulate inflammation, which can be modulated using various factors such as small molecule inhibitors, phytochemicals, recombinant cytokines, and nanoparticles (NPs) in conjugation to phytochemicals to treat cancer. Researchers have identified multiple targets to specifically alter inflammation in cancer therapy to restrict malignant progression and improve the efficacy of cancer therapy. siRNA-and shRNA-loaded NPs have been observed to downregulate STAT3 signaling pathways and have been employed in studies to target tumor malignancies. This review highlights the pathways involved in the interaction between tumor advancement and inflammatory progression, along with the novel approaches of nanotechnology-based drug delivery systems currently used to target inflammatory signaling pathways to combat cancer.

Recent Updates on Viral Oncogenesis: Available Preventive and Therapeutic Entities.

Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Several recent findings revealed cellular and molecular pathways that promote the development and initiation of malignancy when viruses cause an infection. Even, antiviral treatment has become an approach to eliminate the viral infections and prevent the activation of oncogenesis. Therefore, for a better understanding, the molecular pathogenesis of various oncogenic viruses like, hepatitis virus, human immunodeficiency viral (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV), could be explored, especially, to expand many potent antivirals that may escalate the apoptosis of infected malignant cells while sparing normal and healthy ones. Moreover, contemporary therapies, such as engineered antibodies antiviral agents targeting signaling pathways and cell biomarkers, could inhibit viral oncogenesis. This review elaborates the recent advancements in both natural and synthetic antivirals to control viral oncogenesis. The study also highlights the challenges and future perspectives of using antivirals in viral oncogenesis.

Chitosan Nanoparticles-Based Cancer Drug Delivery: Application and Challenges.

Chitin is the second most abundant biopolymer consisting of N-acetylglucosamine units and is primarily derived from the shells of marine crustaceans and the cell walls of organisms (such as bacteria, fungi, and algae). Being a biopolymer, its materialistic properties, such as biodegradability, and biocompatibility, make it a suitable choice for biomedical applications. Similarly, its deacetylated derivative, chitosan, exhibits similar biocompatibility and biodegradability properties, making it a suitable support material for biomedical applications. Furthermore, it has intrinsic material properties such as antioxidant, antibacterial, and antitumor. Population studies have projected nearly 12 million cancer patients across the globe, where most will be suffering from solid tumors. One of the shortcomings of potent anticancer drugs is finding a suitable cellular delivery material or system. Therefore, identifying new drug carriers to achieve effective anticancer therapy is becoming essential. This paper focuses on the strategies implemented using chitin and chitosan biopolymers in drug delivery for cancer treatment.

Specific targeting cancer cells with nanoparticles and drug delivery in cancer therapy.

Nanotechnology has been the latest approach for diagnosis and treatment for cancer, which opens up a new alternative therapeutic drug delivery option to treat disease. Nanoparticles (NPs) display a broad role in cancer diagnosis and has various advantages over the other conventional chemotherapeutic drug delivery. NPs possess more specific and efficient drug delivery to the targeted tissue, cell, or organs and minimize the risk of side effects. NPs undergo passive and active mode of drug targets to tumor area with less elimination of the drug from the system. Size and surface characteristics of nanoparticles play a crucial role in modulating nanocarrier efficiency and the biodistribution of chemo drugs in the body. Several types of nanocarriers, such as polymers, dendrimers, liposome-based, and carbon-based, are studied widely in cancer therapy. Although FDA approved very few nanotechnology drugs for cancer therapy, a large number of studies are undergoing for the development of novel nanocarriers for potent cancer therapy. In this review, we discuss the details of the nano-based therapeutics and diagnostics strategies, and the potential use of nanomedicines in cancer therapy and cancer drug delivery.

Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer.

Head and neck cancer is the sixth most common cancer across the globe. This is generally associated with tobacco and alcohol consumption. Cancer in the pharynx majorly arises through human papillomavirus (HPV) infection, thus classifying head and neck squamous cell carcinoma (HNSCC) into HPV-positive and HPV-negative HNSCCs. Aberrant, mesenchymal-epithelial transition factor (c-MET) signal transduction favors HNSCC progression by stimulating proliferation, motility, invasiveness, morphogenesis, and angiogenesis. c-MET upregulation can be found in the majority of head and neck squamous cell carcinomas. c-MET pathway acts on several downstream effectors including phospholipase C gamma (PLCγ), cellular Src kinase (c-Src), phosphotidylinsitol-3-OH kinase (PI3K), alpha serine/threonine-protein kinase (Akt), mitogen-activated protein kinase (MAPK), and wingless-related integration site (Wnt) pathways. c-MET also establishes a crosstalk pathway with epidermal growth factor receptor (EGFR) and contributes towards chemoresistance in HNSCC. In recent years, the signaling communications of c-MET/HGF in metabolic dysregulation, tumor-microenvironment and immune modulation in HNSCC have emerged. Several clinical trials have been established against c-MET/ hepatocyte growth factor (HGF) signaling network to bring up targeted and effective therapeutic strategies against HNSCC. In this review, we discuss the molecular mechanism(s) and current understanding of c-MET/HGF signaling and its effect on HNSCC.

In Silico Analysis of CatSper Family Genes and APOB Gene Regulation in Male Infertility.

Sperm concentration and sperm motility are the two major causes of male infertility. Having spermatozoa in semen without motility or flagellum tail defect is a major concern needed to be investigated. The CatSper genes are the novel family of four sperm-specific Ca2+-permeable channels which plays an important role in sperm motility, acrosome reaction, sperm, and oocyte fusion. CatSper1, CatSper2, and CatSper3 are very well-studied genes for their role in asthenozoospermia, but the association of these genes with metabolic genes is still unstudied. Another unrevealed aspect is how ROS alter the function of CatSper genes. Among the Catsper family genes, the role of CatSper4 gene must be explored more. In this study, we have used the in silico approach to find the connection between the CatSper family gene with glycolytic genes and also the involvement of CATSPER4 protein in sperm flagellum using the STRING database. Connection of CATSPER1 protein with lipid metabolic gene is also found in Reactome database, and after that gene ontology of these genes was done by using DAVID and Enrichr databases. This analysis showed a strong interaction between CATSPER1, CATSPER2, and CATSPER3 protein with glycolytic protein (i.e., GAPDHS and PGK2), and CATSPER4 protein shows strong relation in the function of sperm flagellum. We also found a novel gene, i.e., APOB contributing to sperm motility. Gene ontology showed the role of APOB and glycolytic proteins in sperm motility. Enrichr analysis showed the association of APOB and glycolytic proteins in asthenozoospermia and CATSPER4 protein with sperm flagellum. Elsevier Pathway Collection also showed proteins involved in male infertility (i.e., GAPDHS). Therefore, we report the role of the CatSper4 gene in sperm tail function and the APOB novel gene involved in sperm motility. Understanding the molecular mechanism(s) of regulations of the CatSper family gene will help us to develop new therapeutic approaches in infertile males.

Arsenic-Induced Sex Hormone Disruption: An Insight into Male Infertility.

Arsenic (As) is one of the most potent natural as well as anthropogenic metalloid toxicants that have various implications in the everyday life of humans. It is found in several chemical forms such as inorganic salt, organic salt, and arsine (gaseous form). Although it is mostly released via natural causes, there are many ways through which humans come in contact with As. Drinking water contamination by As is one of the major health concerns in various parts of the world. Arsenic exposure has the ability to induce adverse health effects including reproductive problems. Globally, around 15% of the couples are affected with infertility, of which about 20-30% are attributed to the male factor. Arsenic affects the normal development and function of sperm cells, tissue organization of the gonads, and also the sex hormone parameters. Stress induction is one of the implications of As exposure. Excessive stress leads to the release of glucocorticoids, which impact the oxidative balance in the body leading to overproduction of reactive oxygen species (ROS). This may in turn result in oxidative stress (OS) ultimately interfering with normal sperm and hormonal parameters. This study deals with As-induced OS and its association with sex hormone disruption as well as its effect on sperm and semen quality.

Bacteriospermia and Male Infertility: Role of Oxidative Stress.

Male infertility is one of the major challenging and prevalent diseases having diverse etiologies of which bacteriospermia play a significant role. It has been estimated that approximately 15% of all infertility cases are due to infections caused by uropathogens and in most of the cases bacteria are involved in infection and inflammation leading to the development of bacteriospermia. In response to bacterial load, excess infiltration of leukocytes in the urogenital tract occurs and concomitantly generates oxidative stress (OS). Bacteria may induce infertility either by directly interacting with sperm or by generating reactive oxygen species (ROS) and impair sperm parameters such as motility, volume, capacitation, hyperactivation. They may also induce apoptosis leading to sperm death. Acute bacteriospermia is related with another clinical condition called leukocytospermia and both compromise male fertility potential by OS-mediated damage to sperm leading to male infertility. However, bacteriospermia as a clinical condition as well as the mechanism of action remains poorly understood, necessitating further research in order to understand the role of individual bacterial species and their impact in male infertility.

Metabolic Dysregulation and Sperm Motility in Male Infertility.

Nowadays, about 14% of couples have difficulty in conceiving, and half of the cases are attributed to men. Asthenozoospermia or poor sperm motility is considered as the cause of infertility in males which is most common. Even though energy metabolism is considered the main reason for the etiology of asthenospermia, few attempts are made to determine the pathway of its metabolic potential. Recognition of cellular as well as molecular pathways that lead to reduced sperm motility may lead to the implementation of new therapeutic strategies to eliminate low sperm motility in people with asthenozoospermia. This review article discusses the key causes of decreased sperm motility and some of the muted genes and metabolic causes of the same.

Pathogenesis of Viral Infections and Male Reproductive Health: An Evidence-Based Study.

Viruses, being intracellular obligate parasites, can cause several congenital and sexually transmitted diseases. Depending on the site of infection, viruses can adopt various pathogenic mechanisms for their survival and to escape the host immune response. The male reproductive system is one of the attainable targets of many viruses including immunodeficiency virus (HIV), Zika virus (ZIKV), adenovirus, cytomegalovirus (CMV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and infection with such viruses may cause serious health issues. Leydig cells and seminiferous tubules are the prime sites of mammalian testis for viral infection. The azoospermic condition is a common symptom of viral infection, wherein the hypothalamic-pituitary-testicular (HPT) axis can be disrupted, leading to decreased levels of luteinizing hormone (LH). Furthermore, oxidative stress (OS) is a major contributing factor to viral infection-associated male infertility. The likelihood of direct and indirect infection, as well as sex-based variability in the vulnerability pattern to viral infections, has been observed. However, there appears to be a long-term impact of viral infection on male reproductive performance due to testicular tissue pathogenicity - a process that requires thorough investigation. The present study aimed to explore how the viruses affect the male reproductive system, including their distribution in tissues and body fluids, possible targets as well as the effects on the endocrine system. We used the major electronic databases such as MEDLINE and SCOPUS. Google Scholar was also consulted for additional literature search related to the topic. Obtained literatures were sorted based on the content. The articles that reported the pathogenesis of viruses on male reproductive health and were published in the English language were included in the present study.

Effect of Environmental Stressors, Xenobiotics, and Oxidative Stress on Male Reproductive and Sexual Health.

This article examines the environmental factor-induced oxidative stress (OS) and their effects on male reproductive and sexual health. There are several factors that induce OS, i.e. radition, metal contamination, xenobiotic compounds, and cigarette smoke and lead to cause toxicity in the cells through metabolic or bioenergetic processes. These environmental factors may produce free radicals and enhance the reactive oxygen species (ROS). Free radicals are molecules that include oxygen and disbalance the amount of electrons that can create major chemical chains in the body and cause oxidation. Oxidative damage to cells may impair male fertility and lead to abnormal embryonic development. Moreover, it does not only cause a vast number of health issues such as ageing, cancer, atherosclerosis, insulin resistance, diabetes mellitus, cardiovascular diseases, ischemia-reperfusion injury, and neurodegenerative disorders but also decreases the motility of spermatozoa while increasing sperm DNA damage, impairing sperm mitochondrial membrane lipids and protein kinases. This chapter mainly focuses on the environmental stressors with further discussion on the mechanisms causing congenital impairments due to poor sexual health and transmitting altered signal transduction pathways in male gonadal tissues.

Oxidative Stress-Induced Male Infertility: Role of Antioxidants in Cellular Defense Mechanisms.

Male infertility is linked to several environmental and mutagenic factors. Most of these factors, i.e., lifestyle, radiations, and chemical contaminations, work on the fundamental principles of physics, chemistry, and biology. Principally, it may induce oxidative stress (OS) and produce free radicals within the cells. The negative effect of OS may enhance the reactive oxygen species (ROS) levels in male reproductive organs and impair basic functions in a couple's fertility. Evidence suggests that infertile men have significantly increased ROS levels and a reduced antioxidant capacity compared with fertile men. Although, basic spermatic function and fertilizing capacity depend on a delicate balance between physiological activity of ROS and antioxidants to protect from cellular oxidative injury in sperm, that is essential to achieve pregnancy. The ideal oxidation-reduction (REDOX) equilibrium requires a maintenance of a range of ROS concentrations and modulation of antioxidants. For this reason, the chapter focuses on the effects of ROS in sperm functions and the current concepts regarding the benefits of medical management in men with diminished fertility and amelioration of the effect to improve sperm function. Also, this evidence-based study suggests an increasing rate of infertility that poses a global challenge for human health, urging the need of health care professionals to offer a correct diagnosis, comprehension of the process, and an individualized management of the patients.

Biological databases and tools for neurological disorders.

Computational approach to study of neuronal impairment is rapidly evolving, as experiments and intuition alone could not explain the complexity of brain system. The increase in an overwhelming amount of new data from both theory and computational modeling necessitate the development of databases and tools for analysis, visualization, and interpretation of neuroscience data. To ensure the sustainability of this development, consistent update and training of young professionals are imperative. For this purpose, relevant articles, chapters, and modules are essential to keep abreast of developments. Therefore, this article seeks to outline the biological databases and analytical tools along with their applications. It's envisaged that knowledge along this line would be a "training recipe" for young talents and guide for professionals and researchers in neuroscience.

Clinical Potential of Himalayan Herb Bergenia ligulata: An Evidence-Based Study.

Herbal products have been used in traditional systems of medicine and by ethnic healers for ages to treat various diseases. Currently, it is estimated that about 80% of people worldwide use herbal traditional medicines against various ailments, partly due to easy accessibility and low cost, and the lower side effects they pose. Bergenia ligulata, a herb ranging from the Himalayas to the foothills, including the north-eastern states of India, has traditionally been used as a remedy against various diseases, most prominently kidney stones. The medicinal properties of B. ligulata have been attributed to bergenin, its most potent bioactive component. Apart from bergenin, the other compounds available in B. ligulata are arbutin, gallic acid, protocatechuic acid, chlorogenic acid, syringic acid, catechin, ferulic acid, afzelechin, paashaanolactone, caryophyllene, 1,8-cineole, ß-eudesmol, stigmasterol, ß-sitosterol, parasorbic acid, 3-methyl-2-buten-1-ol, phytol, terpinen-4-ol, tannic acid, isovalaric acid, avicularin, quercetin, reynoutrin, and sitoinoside I. This review summarizes various medicinal properties of the herb, along with providing deep insight into its bioactive molecules and their potential roles in the amelioration of human ailments. Additionally, the possible mechanism(s) of action of the herb's anti-urolithiatic, antioxidative, antipyretic, anti-diabetic, anti-inflammatory and hepatoprotective properties are discussed. This comprehensive documentation will help researchers to better understand the medicinal uses of the herb. Further studies on B. ligulata can lead to the discovery of new drug(s) and therapeutics for various ailments.

Neuroprotective Potential of Limonene and Limonene Containing Natural Products.

Limonene is a monoterpene confined to the family of Rutaceae, showing several biological properties such as antioxidant, anti-inflammatory, anticancer, antinociceptive and gastroprotective characteristics. Recently, there is notable interest in investigating the pharmacological effects of limonene in various chronic diseases due to its mitigating effect on oxidative stress and inflammation and regulating apoptotic cell death. There are several available studies demonstrating the neuroprotective role of limonene in neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, epilepsy, anxiety, and stroke. The high abundance of limonene in nature, its safety profile, and various mechanisms of action make this monoterpene a favorable molecule to be developed as a nutraceutical for preventive purposes and as an alternative agent or adjuvant to modern therapeutic drugs in curbing the onset and progression of neurodegenerative diseases. This manuscript presents a comprehensive review of the available scientific literature discussing the pharmacological activities of limonene or plant products containing limonene which attribute to the protective and therapeutic ability in neurodegenerative disorders. This review has been compiled based on the existing published articles confined to limonene or limonene-containing natural products investigated for their neurotherapeutic or neuroprotective potential. All the articles available in English or the abstract in English were extracted from different databases that offer an access to diverse journals. These databases are PubMed, Scopus, Google Scholar, and Science Direct. Collectively, this review emphasizes the neuroprotective potential of limonene against neurodegenerative and other neuroinflammatory diseases. The available data are indicative of the nutritional use of products containing limonene and the pharmacological actions and mechanisms of limonene and may direct future preclinical and clinical studies for the development of limonene as an alternative or complementary phytomedicine. The pharmacophore can also provide a blueprint for further drug discovery using numerous drug discovery tools.

Radiations and male fertility.

During recent years, an increasing percentage of male infertility has to be attributed to an array of environmental, health and lifestyle factors. Male infertility is likely to be affected by the intense exposure to heat and extreme exposure to pesticides, radiations, radioactivity and other hazardous substances. We are surrounded by several types of ionizing and non-ionizing radiations and both have recognized causative effects on spermatogenesis. Since it is impossible to cover all types of radiation sources and their biological effects under a single title, this review is focusing on radiation deriving from cell phones, laptops, Wi-Fi and microwave ovens, as these are the most common sources of non-ionizing radiations, which may contribute to the cause of infertility by exploring the effect of exposure to radiofrequency radiations on the male fertility pattern. From currently available studies it is clear that radiofrequency electromagnetic fields (RF-EMF) have deleterious effects on sperm parameters (like sperm count, morphology, motility), affects the role of kinases in cellular metabolism and the endocrine system, and produces genotoxicity, genomic instability and oxidative stress. This is followed with protective measures for these radiations and future recommendations. The study concludes that the RF-EMF may induce oxidative stress with an increased level of reactive oxygen species, which may lead to infertility. This has been concluded based on available evidences from in vitro and in vivo studies suggesting that RF-EMF exposure negatively affects sperm quality.

Ten gigahertz microwave radiation impairs spatial memory, enzymes activity, and histopathology of developing mice brain.

For decades, there has been an increasing concern about the potential hazards of non-ionizing electromagnetic fields that are present in the environment and alarming as a major pollutant or electro-pollutant for health risk and neuronal diseases. Therefore, the objective of the present study was to explore the effects of 10 GHz microwave radiation on developing mice brain. Two weeks old mice were selected and divided into two groups (i) sham-exposed and (ii) microwave-exposed groups. Animals were exposed for 2 h/day for 15 consecutive days. After the completion of exposure, within an hour, half of the animals were autopsied immediately and others were allowed to attain 6 weeks of age for the follow-up study. Thereafter results were recorded in terms of various biochemical, behavioral, and histopathological parameters. Body weight result showed significant changes immediately after treatment, whereas non-significant changes were observed in mice attaining 6 weeks of age. Several other endpoints like brain weight, lipid peroxidation, glutathione, protein, catalase, and superoxide dismutase were also found significantly (p < 0.05) altered in mice whole brain. These significant differences were found immediately after exposure and also in follow-up on attaining 6 weeks of age in microwave exposure group. Moreover, statistically significant (p < 0.001) effect was investigated in spatial memory of the animals, in learning to locate the position of platform in Morris water maze test. Although in probe trial test, sham-exposed animals spent more time in searching for platform into the target quadrant than in opposite or other quadrants. Significant alteration in histopathological parameters (qualitative and quantitative) was also observed in CA1 region of the hippocampus, cerebral cortex, and ansiform lobule of cerebellum. Results from the present study concludes that the brain of 2 weeks aged mice was very sensitive to microwave exposure as observed immediately after exposure and during follow-up study at 6 weeks of age.

Microwave radiation (2.45 GHz)-induced oxidative stress: Whole-body exposure effect on histopathology of Wistar rats.

Man-made microwave and radiofrequency (RF) radiation technologies have been steadily increasing with the growing demand of electronic appliances such as microwave oven and cell phones. These appliances affect biological systems by increasing free radicals, thus leading to oxidative damage. The aim of this study was to explore the effect of 2.45 GHz microwave radiation on histology and the level of lipid peroxide (LPO) in Wistar rats. Sixty-day-old male Wistar rats with 180 ± 10 g body weight were used for this study. Animals were divided into two groups: sham exposed (control) and microwave exposed. These animals were exposed for 2 h a day for 35 d to 2.45 GHz microwave radiation (power density, 0.2 mW/cm2). The whole-body specific absorption rate (SAR) was estimated to be 0.14 W/kg. After completion of the exposure period, rats were sacrificed, and brain, liver, kidney, testis and spleen were stored/preserved for determination of LPO and histological parameters. Significantly high level of LPO was observed in the liver (p < 0.001), brain (p < 0.004) and spleen (p < 0.006) in samples from rats exposed to microwave radiation. Also histological changes were observed in the brain, liver, testis, kidney and spleen after whole-body microwave exposure, compared to the control group. Based on the results obtained in this study, we conclude that exposure to microwave radiation 2 h a day for 35 d can potentially cause histopathology and oxidative changes in Wistar rats. These results indicate possible implications of such exposure on human health.

Titanium dioxide nanoparticles provide protection against polycyclic aromatic hydrocarbon BaP and chrysene-induced perturbation of DNA repair machinery: A computational biology approach.

We examined the interaction of polycyclic hydrocarbons (PAHs) like benzo-α-pyrene (BaP), chrysene, and their metabolites 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene,9,10-oxide (BPDE) and chrysene 1,2-diol-3,4-epoxide-2 (CDE), with the enzymes involved in DNA repair. We investigated interaction of 120 enzymes with PAHs and screened out 40 probable targets among DNA repair enzymes, on the basis of higher binding energy than positive control. Out of which, 20 enzymes lose their function in the presence of BaP, chrysene, and their metabolites, which may fetter DNA repair pathways resulting in damage accumulation and finally leading to cancer formation. We propose the use of nanoparticles as a guardian against the PAH's induced toxicity. PAHs enter the cell via aryl hydrocarbon receptor (AHR). TiO2 NP showed a much higher docking score with AHR (12,074) as compared with BaP and chrysene with AHR (4,600 and 4,186, respectively), indicating a preferential binding of TiO2 NP with the AHR. Further, docking of BaP and chrysene with the TiO2 NP bound AHR complex revealed their strong adsorption on TiO2 NP itself, and not on their original binding site (at AHR). TiO2 NPs thereby prevent the entry of PAHs into the cell via AHR and hence protect cells against the deleterious effects induced by PAHs.