Browsing by Author "Archisman Mahapatra"

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An insight into the molecular mechanisms of persistent organic pollutants (POPs) mediated dysregulation of glucose and lipid homeostasis in Heteropneustes fossilis
(Academic Press Inc., 2025) Shubhendu Shekhar Ray; Archisman Mahapatra; Priya Gupta; Anjali Suman; Rahul Kumar Singh
The study emphasises how ubiquitous persistent organic pollutants (POPs) are and how terrible they are for the environment, specifically because of their tendency to build up in living things and cause a variety of health problems, including diabetes, obesity, and cardiovascular disorders. Due to POPs affinity for lipid-rich tissues, they accumulate in a variety of organs, where they cause metabolic disruption and initiate various anabolic pathways. Studies that use fish as a model organism clarify the metabolic effects of POPs, demonstrating non-adipose lipid accumulation and abnormal glucose homeostasis. Further research on molecular mechanisms shows that POPs interact with gluconeogenic enzymes, causing blood glucose levels to rise. These results are supported by histological and biochemical examinations of fish exposed to POPs, which show changes in lipid composition and cause cellular damage. Molecular docking computational studies demonstrate POPs propensity for binding to gluconeogenic enzymes, providing insight into their potential to promote hyperglycaemia. This study provides a thorough summary of POPs harmful effects on organisms, highlighting their molecular and toxicological, impacts while arguing for better knowledge of their toxicity to vertebrates’ developing embryos. © 2025 Elsevier Inc.
Click inspired novel pyrazole-triazole-persulfonimide & pyrazole-triazole-aryl derivatives; Design, synthesis, DPP-4 inhibitor with potential anti-diabetic agents
(Academic Press Inc., 2022) Manisha Nidhar; Shaziya Khanam; Priyanka Sonker; Priya Gupta; Archisman Mahapatra; Swaraj Patil; Brijesh Kumar Yadav; Rahul Kumar Singh; Ashish Kumar Tewari
This work presented the first report on designing, synthesizing of novel pyrazole-triazole-persulfonimide (7a-i) and pyrazole-triazole-aryl derivatives (8a-j) via click reaction using CuI catalyst and evaluated for their anti-diabetic activity and DPP-4 inhibitory effect. Click reactions went smoothly with CuI catalyst in the presence of tridentate chelating ligands and produced copper-free target pyrazole-triazole-persulfonimide analogues in excellent yield at RT. The designed compounds were docked against DPP-4 enzyme and showed excellent interaction with active amino acids residue. Further, all novel pyrazole-triazole-persulfonimide and pyrazole-triazole derivatives were subjected to enzyme-based in vitro DPP-4 inhibitory activity. Based on the SAR study DPP-4 inhibitory capacity compounds 7f (9.52 nM) and 8h (4.54 nM) possessed the significant inhibition of DPP-4. Finally compounds 7f and 8h were evaluated for their in vivo anti-diabetic activity using STZ induced diabetic mice model, and 8h showed a significant diabetic control effect compared to the sitagliptin drug. These studies demonstrated that the novel pyrazole-triazole-persulfonimide and pyrazole-triazole-aryl derivatives might be used as the leading compounds to develop novel DPP-4 inhibitors as potential anti-diabetic agents. © 2022 Elsevier Inc.
Elucidating the impact of persistent organic pollutants on male reproductive health and testicular structure
(Elsevier Ireland Ltd, 2025) Shubhendu Shekhar Ray; Priya Gupta; Archisman Mahapatra; Anjali Suman; Rahul Kumar Singh
Persistent organic pollutants (POPs) are environmental contaminants that pose significant health risks due to their widespread distribution. This study examines the effects of POPs on male reproductive health using realistic human exposure scenarios. Male mice exposed to 28 ng of POPs for 35 days exhibited detrimental effects on sperm motility and count, significant changes in germ cell composition, and compromised steroidogenesis. Histopathological analyses revealed testicular architecture alterations and abnormal lipid accumulation in the interstitial space, potentially hindering steroidogenesis and Leydig cell function. Western blot and immunofluorescence studies showed reduced levels of steroidogenic markers. Flow cytometry indicated a decrease in round spermatids, suggesting impaired spermatogenesis. Molecular investigations revealed reduced mRNA expression of critical steroidogenic enzymes, while increased apoptotic markers and DNA fragmentation suggested apoptosis as a mechanism. This study highlights the need for stricter regulations and improved environmental health policies to mitigate the adverse effects of POPs on male reproductive health. © 2025 Elsevier B.V.
In silico and in vivo assessment of developmental toxicity, oxidative stress response & Na+/K+-ATPase activity in zebrafish embryos exposed to cypermethrin
(Academic Press, 2023) Priya Gupta; Archisman Mahapatra; Anjali Suman; Rahul Kumar Singh
Cypermethrin (CYP), a synthetic type II pyrethroid pesticide, is extensively used to control pests in industrial, domestic, and agricultural environments. However, its indiscriminate use leads to a potential threat to aquatic organisms. Although several reports focussed on developmental toxicity effects, a concise study combining cardiotoxicity along with Na+/K+-ATPase activity and molecular docking of developmental proteins with CYP was lacking. This present study was designed to address this gap to comprehend the impact of CYP exposure (0, 25, 100 and 200 µg/L) on embryonic zebrafish. As a result, CYP delayed the hatching rate, reduced heart rate, increased mortality rate and induced numerous morphological abnormalities. Subsequently, CYP induced oxidative stress in treated zebrafish embryos with the concomitant increase in antioxidant enzymes (SOD and CAT) and malondialdehyde production. In addition, an alteration in AChE, NO content and Na+/K+-ATPase activity was observed, suggesting a disruption in cardiac development and ion regulation. Furthermore, AO staining showed notable apoptotic cells which are supported by alteration in apoptosis-related gene expressions. Moreover, to explore the putative targets of CYP, computational docking with developmental proteins (WNT3A, WNT8A, GATA-4, Nkx 2–5 and ZHE1) showed strong interactions and binding. Taken together, our findings provide a better understanding of assessing the ecotoxicological risk information and the mode of action underlying the development of teleost fishes following CYP exposure. Meanwhile, the pioneering nature of this study is to emphasize the future use of Na+/K+-ATPase activity as a potential toxicity biomarker and in silico molecular docking studies to complement developmental toxicity findings. © 2023
Lead modification via computational studies: Synthesis of pyrazole-containing β-amino carbonyls for the treatment of type 2 diabetes
(John Wiley and Sons Inc, 2023) Manisha Nidhar; Vipin Kumar; Archisman Mahapatra; Priya Gupta; Priyanka Yadav; Priyanka Sonker; Akhilesh Kumar; Shweta Mishra; Rahul Kumar Singh; Ashish Kumar Tewari
This article describes studies on the design, synthesis, and biological evaluation of pyrazole-containing β-amino carbonyl compounds (5a–5q) as DPP-4 inhibitors and anti-diabetic agents. In contrast, mannich reactions went smoothly with bismuth nitrate (Bi (NO3)3) catalyst in the presence of ethanol and produced pyrazole-containing β-amino carbonyl compounds in good yield. Molecular docking studies of designed derivatives with DPP-4 enzyme (PDB: 2OLE), compounds 5d, 5h, 5j, and 5k showed excellent interaction. 3D QSAR and pharmacophoric model studies were also carried out. ADMET parameters, pharmacokinetic properties, and in vivo toxicity studies further confirmed that all the designed compounds were found to have good bioavailability and were less toxic. Further, these compounds were evaluated as enzyme-based in vitro DPP-4 inhibitory activity, and 5d, 5h, 5i, 5j, and 5k exhibited IC50 toward DPP-4 enzyme of 10.52, 10.41, 5.55, 4.16, and 7.5 nM, respectively. The most potent compound, 5j, was further selected for in vivo anti-diabetic activity using an STZ-induced diabetic mice model, and 5j showed a significant diabetic control effect. © 2022 John Wiley & Sons Ltd.
Ligand-based designing of DPP-4 inhibitors via hybridization; synthesis, docking, and biological evaluation of pyridazine-acetohydrazides
(Institute for Ionics, 2023) Manisha Nidhar; Vipin Kumar; Archisman Mahapatra; Priya Gupta; Brijesh Kumar Yadav; Rahul Kumar Singh; Ashish Kumar Tewari
Abstract: A series of novel pyridazine-acetohydrazide hybrids were designed, synthesized, and evaluated for their in vitro and in vivo antihyperglycemic activity. In this context, pyridazine-acetohydrazides (6a–6p) were synthesized by coupling substituted aldehyde with 2-(5-cyano-6-oxo-3,4-diphenylpyridazine-1-6H-yl) acetohydrazide, which was prepared via the reaction of pyridazine ester with hydrazine hydrate. The molecular docking study was carried out to examine the binding affinities and interaction of designed compounds against the DPP-4 enzyme. Compounds 6e, 6f, 6l, and 6n exhibited interaction with active residue. In silico ADMET properties, and toxicity studies corroborated that compounds were found to have good bioavailability and less toxic. The synthesized compounds were further estimated for in vitro DPP-4 activity. Compounds 6e and 6l were found as the most effective DPP-4 inhibitor in this series with IC50 values (6.48, 8.22 nM) when compared with sitagliptin (13.02 nM). According to the toxicity assay compound, 6l showed very less toxicity at a higher concentration so further selected for the in vivo antihyperglycemic activity. Graphical abstract: [Figure not available: see fulltext.]. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
PFOS-induced dyslipidemia and impaired cholinergic neurotransmission in developing zebrafish: Insight into its mechanisms
(Elsevier Inc., 2023) Archisman Mahapatra; Priya Gupta; Anjali Suman; Shubhendu Shekhar Ray; Rahul Kumar Singh
Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that has been widely detected in the environment and is known to accumulate in organisms, including humans. The study investigated dose-dependent mortality, hatching rates, malformations, lipid accumulation, lipid metabolism alterations, and impacts on cholinergic neurotransmission. Increasing PFOS concentration led to higher mortality, hindered hatching, and caused concentration-dependent malformations, indicating severe abnormalities in developing zebrafish. The results also demonstrated that PFOS exposure led to a significant increase in total lipids, triglycerides, total cholesterol, and LDL in a concentration-dependent manner, while HDL cholesterol levels were significantly decreased. Additionally, PFOS exposure led to a significant decrease in glucose levels. The study identified TGs, TCHO, and glucose as the most sensitive biomarkers in assessing lipid metabolism alterations. The study also revealed altered expression of genes involved in lipid metabolism, including upregulation of fasn, acaca, and hmgcr and downregulation of ldlr, pparα, and abca1, as well as decreased lipoprotein lipase (LPL) and increased fatty acid synthase (FAS) activity,suggesting an impact on fatty acid synthesis, cholesterol uptake, and lipid transport. Additionally, PFOS exposure led to impaired cholinergic neurotransmission, evidenced by a concentration-dependent inhibition of acetylcholinesterase activity, altered gene expressions related to neural development and function, and reduced Na+/K+-ATPase activity. STRING network analysis highlighted two distinct gene clusters related to lipid metabolism and cholinergic neurotransmission, with potential interactions through the pparα-creb1 pathway. Overall, this study provide important insights into the potential health risks associated with PFOS exposure, including dyslipidemia, cardiovascular disease, impaired glucose metabolism, and neurotoxicity. Further research is needed to fully elucidate the underlying mechanisms and potential long-term effects of PFOS exposure. © 2023 Elsevier Inc.
Polystyrene microplastics disrupt female reproductive health and fertility via sirt1 modulation in zebrafish (Danio rerio)
(Elsevier B.V., 2023) Priya Gupta; Archisman Mahapatra; Anjali Suman; Shubhendu Shekhar Ray; Guilherme Malafaia; Rahul Kumar Singh
Microplastics (MPs) pollution poses an emerging threat to aquatic biota, which could hinder their physiological processes. Recently various evidence has demonstrated the toxic impacts of MPs on cellular and organismal levels, but still, the underlying molecular mechanism behind their toxicity remains ambiguous. The hypothalamic-pituitary-gonadal (HPG) axis regulates the synthesis and release of sex steroid hormones, and SIRT1 plays a vital role in this process. The current study aimed to elucidate the harmful effects of MPs on female reproduction via SIRT1 modulation. Healthy female zebrafish were exposed to different concentrations (50 and 500 µg/L) of polystyrene microplastics (PS-MPs). The results revealed a significant change in the gonadosomatic index (GSI) after exposure to PS-MPs. In addition, the decreased fecundity rate displayed an evident dosage effect, indicating that exposure to PS-MPs causes deleterious effects on fertilization. Furthermore, significantly enhanced levels of reactive oxygen species (ROS) and apoptotic signals through the TUNEL assay were evaluated in different treated groups. Moreover, morphological alterations in the gonads of zebrafish exposed to MPs were also observed through H&E staining. The subsequent change in plasma steroid hormone levels (E2/T ratio) showed an imbalance in hormonal homeostasis. Meanwhile, to follow PS-MPs’ effects on the HPG axis via SIRT1 modulation and gene expression related to steroidogenesis, SIRT1/p53 pathway was evaluated through qPCR. The altered transcription levels of genes indicated the plausible interference of PS-MPs on the HPG axis function. Our in-silico molecular docking study proves that PS-MPs efficiently bind and inhibit endocrine receptors and SIRT1. Thus, these findings add to our understanding of the probable molecular mechanisms of reproductive impairment caused by PS-MPs in zebrafish. © 2023 Elsevier B.V.
Polystyrene microplastics induced disturbances in neuronal arborization and dendritic spine density in mice prefrontal cortex
(Elsevier Ltd, 2024) Anjali Suman; Archisman Mahapatra; Priya Gupta; Shubhendu Shekhar Ray; Rahul Kumar Singh
An increasing use of plastics in daily life leads to the accumulation of microplastics (MPs) in the environment, posing a serious threat to the ecosystem, including humans. It has been reported that MPs cause neurotoxicity, but the deleterious effect of polystyrene (PS) MPs on neuronal cytoarchitectural morphology in the prefrontal cortex (PFC) region of mice brain remains to be established. In the present study, Swiss albino male mice were orally exposed to 0.1, 1, and 10 ppm PS-MPs for 28 days. After exposure, we found a significant accumulation of PS-MPs with a decreased number of Nissl bodies in the PFC region of the entire treated group compared to the control. Morphometric analysis in the PFC neurons using Golgi-Cox staining accompanied by Sholl analysis showed a significant reduction in basal dendritic length, dendritic intersections, nodes, and number of intersections at seventh branch order in PFC neurons of 1 ppm treated PS-MPs. In neurons of 0.1 ppm treated mice, we found only decrease in the number of intersections at the seventh branch order. While 10 ppm treated neurons decreased in basal dendritic length, dendritic intersections, followed by the number of intersections at the third and seventh branch order were observed. As well, spine density on the apical secondary branches along with mRNA level of BDNF was significantly reduced in all the PS-MPs treated PFC neurons, mainly at 1 ppm versus control. These results suggest that PS-MPs exposure affects overall basal neuronal arborization, with the highest levels at 1 and 10 ppm, followed by 0.1 ppm treated neurons, which may be related to the down-regulation of BDNF expression in PFC. © 2024 Elsevier Ltd
Polystyrene microplastics modulated bdnf expression triggering neurotoxicity via apoptotic pathway in zebrafish embryos
(Elsevier Inc., 2023) Anjali Suman; Archisman Mahapatra; Priya Gupta; Shubhendu Shekhar Ray; Rahul Kumar Singh
A ubiquitous presence of microplastics and nanoplastics created a new toxicological research area arising concept of “plastic rivers”. But, the precise molecular mechanisms by which its exposure affects developmental neurotoxicity are poorly understood. Hence, in the present investigation, healthy zebrafish embryos were exposed to different concentrations of 500 nm polystyrene microplastics (0.1 ppm, 1 ppm and 10 ppm) to assess the neurotoxicity and the underlying biomolecular mechanism. On the last day of exposure, behaviour, accumulation, embryotoxicity, acridine orange staining, antioxidant enzyme assay, acetylcholinesterase assay, nitric oxide (NO) estimation, along with neurotransmitter (serotonin, dopamine) quantification and gene expression using qRT-PCR (bdnf, p53, bcl-2, caspase-3, caspase-9) were performed. As a result, we found that zebrafish embryos ingest and bioaccumulate microplastic without causing any morphological changes and lethality. The survival and hatching rates of the embryos were also unaffected but the swimming behaviour patterns were found to be altered. Further, acridine orange staining exhibited more apoptosis in treated groups with increased p53, caspase-3, caspase-9 and decreased bcl-2 gene expression. Moreover, polystyrene microplastics exposure resulted in reduced acetylcholinesterase activity leading to elevated NO concentration along with altered serotonin and dopamine levels and subsequently leading to down-regulated bdnf gene expression and modulated downstream apoptotic signalling, confirming the neurotoxicity potential of microplastics causing neuronal dysfunction. This study also compared the binding affinities between styrene and human proteins (Bdnf, p53 and Bcl-2) using bioinformatics methods, and docking results showed negative binding energy resulting in high binding affinities of Bcl-2 then p53 and Bdnf with styrene. © 2023 Elsevier Inc.
Sorption of PFOS onto polystyrene microplastics potentiates synergistic toxic effects during zebrafish embryogenesis and neurodevelopment
(Elsevier Ltd, 2024) Priya Gupta; Archisman Mahapatra; Bharat Manna; Anjali Suman; Shubhendu Shekhar Ray; Naresh Singhal; Rahul Kumar Singh
Microplastics (MPs) have become an emerging anthropogenic pollutant, and their ability to sorb contaminants potentially enhances the threats to the ecosystem. Only a few studies are available to understand the combined effects of microplastics and other pollutants. The present study investigated the sorption of perfluorooctane sulfonic acid (PFOS) onto polystyrene microplastics (PS-MPs) at varying concentrations, using molecular dynamics simulation (MDS) to preliminarily explore the adsorption behavior. The MDS results revealed negative interaction energies between PFOS and PS-MPs, underscoring PS-MPs' role as a potential adsorbent for PFOS in an aqueous solution. Thereafter, zebrafish embryos were employed to explore the toxic effects of combined exposure to PS-MPs and PFOS. Fluorescence and Scanning Electron Microscopy (SEM) suggested PS-MP accumulation individually and in combination with PFOS on the embryonic chorion membrane. As a result, the exposed group showed increased inner pore size of the chorionic membrane and accelerated heartbeat, indicating hypoxic conditions and hindered gaseous exchange. PS-MPs aggravated the toxicity of PFOS during larval development manifested by delayed hatching rate, increased mortality, and malformation rate. Additionally, increased ROS accumulation and altered antioxidant enzymatic status were observed in all the exposed groups suggesting perturbation of the redox state. Additionally, co-exposure of zebrafish larvae to PS-MPs and PFOS resulted in an abrupt behavioral response, which decreased AChE activity and altered neurotransmitter levels. Taken together, our results emphasize that PS-MPs can act as a potential vector for PFOS, exerting synergistic toxic effects in the aquatic environment, and hence their health risks cannot be ignored. © 2024 Elsevier Ltd
Systematic Review and Meta‑analysis of Environmental Toxic Metal Contaminants and the Risk of Ischemic Stroke
(Wolters Kluwer Medknow Publications, 2022) Priya Dev; Priya Gupta; Archisman Mahapatra; Mareena Cyriac; Amit Kumar; Varun Kumar Singh; Vijaya Nath Mishra; Abhishek Pathak
Background: Stroke is the second largest cause of mortality (WHO 2014) and long‑lasting disability worldwide. Many risk factors are associated with stroke, such as age, gender, chronic illnesses, cardiovascular disease, lifestyle, and smoking. With global industrialization, the roles of environmental contaminants and their association with stroke are still unclear and have attracted much more attention. Materials and Methods: We conducted a systematic review on the environmental toxic metal contaminants and the risk of ischemic stroke. A comprehensive literature search was carried out till June 30, 2021 from databases such as PubMed, Science Direct, Embase, and Scopus. The quality of all the articles which met our inclusion criteria was assessed using Newcastle–Ottawa scaling, and four eligible studies were included for our systematic review. Results: The serum and urine cadmium concentrations were positively associated with the risk of ischemic stroke. There was an inverse association of serum and urine concentrations of mercury (Hg), serum concentration of gold and cerium with ischemic stroke, and the serum and urine concentrations of lead (Pb) had no association with ischemic stroke risk. Conclusion: The study showed strong associations between heavy metals and ischemic stroke, but more studies are required to prove the associations. © 2022 Annals of Indian Academy of Neurology.
Toxicopathological impact of sub-lethal concentrations of lead nitrate on the gill of the catfish Heteropneustes fossilis
(Elsevier GmbH, 2022) Archisman Mahapatra; Arup Mistri; Priya Gupta; Sumanta Kar; Swati Mittal; Rahul K. Singh
In recent studies, fish are heavily used as biomarkers of aquatic pollution, and heavy metals are among the main contributors to water pollution. In the present study, we investigated histopathological changes along with alterations in localization and activity of enzymes alkaline phosphatase (ALP), acid phosphatase (ACP), catalase (CAT), peroxidase (PER) and Na+/K+-ATPase in the gill tissues of Indian stinging catfish Heteropneustes fossilis exposed to two different concentrations (0.4 and 4 mg/L) of lead nitrate for 15 days. Histopathological examination of gill tissues revealed hypertrophy and swelling of epithelial cells, the fusion of epithelium of gill filaments and secondary lamellae, and alteration of secondary lamellae structure. Biochemical assays and histochemical localization show a pronounced effect on enzyme alkaline phosphatase activity and acid phosphatase in the gills of both groups of treated groups. In contrast, a significant decrease was noticed in the enzymatic response including catalase and peroxidase activity. Being a vital organ gill reflects the fish's physiological condition and the severity of the contamination in the surrounding environment. Gill is also the prime organ of osmoregulation in teleosts. Decreased activity of Na+/K+-ATPase suggests lead as a potent inhibitor of Na+/K+-ATPase that causes sodium hyperregulation. Alteration in the activity of metabolic enzymes reflects the level of tissue damage and metabolic disruption. At the same time, the increased activity of antioxidant enzymes states the condition of oxidative stress. Haematological parameters also altered with the lead nitrate exposure, reflecting metal toxicity and immune response against it. Meanwhile, this study also provides a potential use of H. fossilis as a biomarker for aquatic pollution. © 2022
Unraveling the mechanisms of perfluorooctanesulfonic acid-induced dopaminergic neurotoxicity and microglial activation in developing zebrafish
(Elsevier B.V., 2023) Archisman Mahapatra; Priya Gupta; Anjali Suman; Shubhendu Shekhar Ray; Guilherme Malafaia; Rahul Kumar Singh
Perfluorooctanesulfonic acid (PFOS) is a prevalent, persistent organic pollutant in environmental matrices, yet its precise mechanism of neurotoxicity remains unclear. This study investigated the developmental and neurobehavioral effects of PFOS exposure (0, 100, 500, and 1000 μg/L) on zebrafish. The findings indicated that PFOS exposure caused various developmental abnormalities, including increased mortality, delayed hatching, shortened body length, bent spine, and edema in the pericardial and yolk sac regions. Subsequently, larvae exhibited a significant decrease in spontaneous movement frequency, altered touch-evoked response, and locomotor behavior. In fact, aberrant cellular responses in the brain and cardiac regions were observed. Microglial activation is a critical component of the inflammatory immune responses related to neurotoxicity. Likewise, our findings indicated that PFOS-induced microglial activation might be responsible for neuronal inflammation and apoptosis. Furthermore, AChE activity and dopamine content at the neurotransmitter level were also disrupted after PFOS exposure. The gene expression of dopamine signaling pathways and neuroinflammation were also altered. Collectively, our findings highlight that PFOS exposure can induce dopaminergic neurotoxicity and neuroinflammation through microglial activation, thus ultimately affecting behavior. Taken together, this study will provide mechanistic effects underlying the pathophysiology of neurological disorders. © 2023 Elsevier B.V.