Biology subjects

Marigoudar, S. R.

Publications and source records attributed to Marigoudar, S. R..

4 recordsLinked to original sources

bioRxiv2024

Network toxicology focused investigation on the impacts of inorganic arsenic and cadmium on human and ecosystem health

Heavy metals like arsenic and cadmium are persistent environmental pollutants that pose serious health risks to humans and ecosystems due to their toxicity, bioaccumulation potential, and frequent presence in consumer products. Network toxicology offers a holistic in silico framework to elucidate the complex biological mechanisms of toxicity, thereby supporting New Approach Methodologies (NAMs) for toxicity assessment. In this study, network toxicological tools were utilized to investigate arsenic- and cadmium-induced toxicities. Toxicity endpoints associated with inorganic arsenic and cadmium compounds were curated from six exposome-relevant databases and mapped to key events (KEs) across adverse outcome pathways (AOPs) cataloged in AOP-Wiki. This led to construction of stressor-AOP networks, revealing 51 AOPs associated with arsenic and 78 with cadmium, and facilitated mechanistic case studies of pathways relevant to human and ecological health. Toxicity concentrations and bioconcentration factors from the ECOTOX database were then used to construct stressor-species networks, that helped identify species that are vulnerable and potentially bioaccumalate these chemicals. Further, the construction of species sensitivity distributions (SSDs) and toxicity-normalized SSDs (SSDn), provided a comparative framework for prioritizing these compounds in risk assessments. Further, integrating SSD data with stressor-species networks identified species groups particularly sensitive to arsenic and cadmium exposure, enhancing these networks utility for ecological risk assessment. The networks and related data generated in this study are freely available for further research at https://cb.imsc.res.in/heavymetaltox/. Overall, this study offers a comprehensive perspective on the toxicological impact of inorganic arsenic and cadmium compounds, supporting a One Health approach to their regulatory and mitigation strategies.

pharmacology and toxicology↗

bioRxiv2024

Network-based investigation of petroleum hydrocarbons-induced ecotoxicological effects and their risk assessment

Petroleum hydrocarbons (PHs) are compounds composed mostly of carbon and hydrogen, originating from crude oil and its derivatives. PHs are primarily released into the environment through the diffusion of oils, resulting from anthropogenic activities like transportation and offshore drilling, and accidental incidents such as oil spills. Once released, these PHs can persist in different ecosystems and cause long-term detrimental ecological impacts. While the hazards associated with such PH contaminations are often assessed by the concentrations of total petroleum hydrocarbons in the environment, studies focusing on the risks associated with individual PHs are limited. Here, we leveraged different network-based frameworks to explore and understand the adverse ecological effects associated with PH exposure. First, we systematically curated a list of 320 PHs from published reports. Next, we integrated biological endpoint data from toxicological databases, and constructed a stressor-centric adverse outcome pathway (AOP) network linking 75 PHs with 177 ecotoxicologically-relevant high confidence AOPs within AOP-Wiki. Further, we relied on stressor-species network constructions, based on reported toxicity concentrations and bioconcentration factors data for 80 PHs and 28 PHs, respectively, and found that crustaceans are documented to be affected by many of these PHs. Finally, we utilized the aquatic toxicity data within ECOTOX to construct species sensitivity distributions for polycyclic aromatic hydrocarbons (PAHs) prioritized by the US EPA, and derived their corresponding hazard concentrations (HC05) that protect 95% of species in the aquatic ecosystem. Overall, this study highlights the importance of using network-based approaches and risk assessment methods to understand the PH-induced toxicities effectively.

pharmacology and toxicology↗

bioRxiv2024

Leveraging integrative toxicogenomic approach towards development of stressor-centric adverse outcome pathway networks for plastic additives

Plastics are widespread pollutants found in atmospheric, terrestrial and aquatic ecosystems due to their extensive usage and environmental persistence. Plastic additives, that are utilized to achieve specific functionality in plastics, leach into the environment upon plastic degradation and pose considerable risk to ecological and human health. Limited knowledge concerning the presence of plastic additives throughout the plastic life cycle has hindered their effective regulation, thereby posing risks to product safety. In this study, we leveraged the adverse outcome pathway (AOP) framework to understand the mechanisms underlying plastic additives-induced toxicities. We first identified an exhaustive list of 6470 plastic additives from chemicals documented to be found in plastics. Next, we leveraged heterogenous toxicogenomics and biological endpoints data from five exposome-relevant resources, and identified associations between 1287 plastic additives and 322 complete and high quality AOPs within AOP-Wiki. Based on these plastic additive-AOP associations, we constructed a stressor-centric AOP network, wherein the stressors are categorized into 10 priority use sectors and AOPs are linked to 27 disease categories. We visualized the plastic additives-AOP network for each of the 1287 plastic additives and made them available in a dedicated website: https://cb.imsc.res.in/saopadditives/. Finally, we showed the utility of the constructed plastic additives-AOP network by identifying 28 highly relevant AOPs associated with benzo[a]pyrene, and thereafter, explored the associated toxicity pathways leading to respiratory and gastrointestinal system diseases in humans and developmental disorders in aquatic species. Overall, the constructed plastic additives-AOP network will enable regulatory risk assessment of plastic additives, thereby contributing towards a toxic-free circular economy for plastics.

pharmacology and toxicology↗

bioRxiv2023

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity

Cadmium is a prominent toxic heavy metal that contaminates both terrestrial and aquatic environments. Owing to its high biological half-life and low excretion rates, cadmium causes a variety of adverse biological outcomes. Adverse outcome pathway (AOP) networks were envisioned to systematically capture toxicological information to enable risk assessment and chemical regulation. Here, we leveraged AOP-Wiki and integrated heterogeneous data from four other exposome-relevant resources to build the first AOP network relevant for inorganic cadmium-induced toxicity. From AOP-Wiki, we filtered 309 high confidence AOPs, identified 312 key events (KEs) associated with inorganic cadmium, and thereafter, curated 30 cadmium relevant AOPs (cadmium-AOPs), using a data-centric approach. By constructing the undirected AOP network, we identified a large connected component of 18 cadmium-AOPs. Further, we analyzed the directed network of 59 KEs and 82 key event relationships (KERs) in the largest component using graph-theoretic approaches. Subsequently, we mined published literature using artificial intelligence-based tools to provide auxiliary evidence of cadmium association for all KEs in the largest component. Finally, we performed case studies to verify the rationality of cadmium-induced toxicity in humans and aquatic species. Overall, cadmium-AOP network constructed in this study will aid ongoing research in systems toxicology and chemical exposome.

pharmacology and toxicology↗