Thallium sulphate (TLM) is a highly hazardous metal known to induce severe renal damage. Syringetin (SGN) is a naturally derived polyphenolic compound that demonstrates excellent medicinal properties. This research trial was conducted to determine the nephroprotective ability of SGN to inhibit TLM induced renal toxicity in rats by assessing different parameters including oxidative stress, apoptotic and inflammatory markers as well as histomorphological parameters. Thirty-two Sprague Dawley rats were apportioned into the control, TLM (6.4 mgkg- 1), TLM (6.4 mgkg- 1) + SGN (10 mgkg- 1) and SGN (10 mgkg- 1) alone administered group. Our findings revealed that TLM exposure promoted renal inflammation which was evident by increased mRNA expression of myeloid differentiation primary response 88 (MYD88), toll-like receptor 4 (TLR4), interleukin-1 beta (IL-1 beta), high mobility group box1 (HMGB1), tumor necrosis factor- alpha (TNF-alpha), receptor for advanced glycation end products (RAGE), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and nuclear factor- kappa B (NF-kappa B). The concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA) were exacerbated while the enzymatic action of heme oxygenase-1 (HO-1), superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT), & tissue contents of glutathione (GSH) were reduced after TLM intoxication. Serum concentrations of N-Acetylglucosamine (NAG), blood urea nitrogen (BUN), Kidney Injury Molecule-1 (KIM-1), Neutrophil Gelatinase-Associated Lipocalin (NGAL), creatinine, uric acid were observed elevated while a notable reduction was noted in the concentration of creatinine clearance following the dose administration of TLM. The levels of Bcl-2-associated X protein (Bax), cysteine-aspartic acid protease-3 (Caspase-3) & cysteine-aspartic acid protease-9 (Caspase-9) were exacerbated while the concentration of B-cell lymphoma-2 (Bcl-2) was notably suppressed following regimen of TLM. Renal tissues were distorted after TLM administration. In contrast, SGN supplementation notably restored oxidative profile, reduced pro-inflammatory and apoptotic markers as well as improved renal histology.

Micro- and nanoplastics (MNPs), pervasive environmental pollutants, contaminate water, soil, air, and the food chain and ultimately accumulate in living organisms. Macrophages are the main immune cells that gather around MNPs and engulf them through the process of phagocytosis. This internalization triggers M1 polarization and the secretion of inflammatory cytokines, including IL-1, IL-18, IL-12, TNF-alpha, and IFN-gamma. Furthermore, MNPs damage mitochondria and lysosomes, causing overactivation of iNOS and excessive production of ROS. This results in cellular stress and induce apoptosis, necroptosis, and, in some cases, metosis in macrophages. The internalization of MNPs also increases the expression of receptors, involving CD36, SR-A, LOX-1, and the macrophage receptor with a collagenous structure (MARCO) while decreasing ABCA-1 and ABCG-1. MNPs in adipose tissue macrophages trigger proinflammatory cytokine secretion, causing adipogenesis, lipid accumulation, insulin resistance, and the secretion of inflammatory cytokines in adipocytes. Various factors influence the rate of MNP internalization by macrophages, including size, charge, and concentration, which affect internalization through passive diffusion. Receptor-mediated phagocytosis of MNPs occurs directly via receptors like T-cell immunoglobulin and mucin domain containing 4 (TIM-4) and MARCO. The attachment of biomolecules, including proteins, antibodies, opsonins, or microbes to MNPs (forming corona structures) promotes indirect receptor-mediated endocytosis, as macrophages possess receptors like TLRs and Fc gamma RIII. MNPs also cause gut dysbiosis, a risk factor for proinflammatory microenvironment and M1 polarization. Here, we review the mechanisms and consequences of MNP macrophage exposure, which is linked to autoimmunity, inflammation, and cardiometabolic syndrome manifestations, including atherosclerosis and obesity, highlighting the immunotoxicity of MNPs.

Cadmium (Cd) is a highly toxic heavy metal contaminant found in soil and water due to human activities such as mining and industrial discharge. Cd can accumulate in the body, leading to various health risks such as organ injuries, osteoporosis, renal dysfunction, Type 2 diabetes (T2DM), reproductive diseases, hypertension, cardiovascular diseases, and cancers. The gut is particularly sensitive to Cd toxicity as it acts as the primary barrier against orally ingested Cd. Even at low concentrations, Cd can cause oxidative stress, inflammation, and intestinal bleeding. Cd also disrupts the gut microbiota, affecting its structure, taxonomic composition, and metabolic functions. Cd exposure alters the structure of the gut microbial community, reducing diversity and upregulating certain phyla and genera. This disturbance can lead to physiological and metabolic imbalances, including disruptions in energy homeostasis, amino acid, lipid, nucleotide, and short-chain fatty acid (SCFAs) metabolism. The effects of Cd on the gut microbiota depend on the duration of exposure, the dose of Cd, and can vary based on sex and age. Cd-induced gut dysbiosis has been linked to various diseases, including diabetes, adiposity, atherosclerosis, liver damage, infections, cancer, and neurodegenerative diseases. Interventions targeting the gut microbiota, such as probiotics, specific diets, melatonin, selenium, vitamin D3, and certain compounds, have shown potential in reducing the health risks associated with Cd exposure. However, combined exposure to Cd and other toxicants, such as microplastics (MPs), heavy metals, and antibiotics, can amplify the toxicity and dysbiosis in the gut microbiota.

Currently, there is a growing concern for human health with the rise of environmental pollution. Water contamination and health problems had been understood. Sanitation-related health issues have been overcome in the greater part of the world. Progressive industrialization has caused a number of new pollutants in water and in the atmosphere. It is a growing concern for the human health, especially upon the reproductive health. Current researchers provide a strong association between the rising concentrations of ambient pollutants and the adverse health impact. Furthermore, the pollutants have the adverse effects upon reproductive health as well. Major concern is for the health of a pregnant woman and her baby. Maternal-fetal inflammatory response due to the pollutants affects the pregnancy outcome adversely. Preterm labor, fetal growth restriction, intrauterine fetal death, and stillbirths have been observed. Varieties of pathological processes including inflammation, endocrine dysfunction, epigenetic changes, oxidative and nitrosative stress, and placental dysfunction have been explained as the biological plausibility. Prospective studies (systematic review and meta-analysis) have established that exposure to particulate matters (PM) and the nanoparticles (NP) leads to excessive oxidative changes to cause DNA mutations, lipid peroxidation and protein oxidation. Progressive industrialization and emergence of heavy metals, micro- (MP) and nanoparticles (NP) in the atmosphere and in water are the cause for concern. However, most of the information is based on studies from industrialized countries. India needs its own country-based study to have the exact idea and to develop the mechanistic pathways for the control.

Soil and water pollution represent significant threats to global health, ecosystems, and biodiversity. Healthy soils underpin terrestrial ecosystems, supporting food production, biodiversity, water retention, and carbon sequestration. However, soil degradation jeopardizes the health of 3.2 billion people, while over 2 billion live in waterstressed regions. Pollution of soil, air, and water is a leading environmental cause of disease, contributing to over 9 million premature deaths annually. Soil contamination stems from heavy metals, synthetic chemicals, pesticides, and plastics, driven by industrial activity, agriculture, and waste mismanagement. These pollutants induce oxidative stress, inflammation, and hormonal disruption, significantly increasing risks for non-communicable diseases (NCDs) such as cardiovascular disease (CVD). Emerging contaminants like micro- and nanoplastics amplify health risks through cellular damage, oxidative stress, and cardiovascular dysfunction. Urbanization and climate change exacerbate soil degradation through deforestation, overfertilization, and pollution, further threatening ecosystem sustainability and human health. Mitigation efforts, such as reducing chemical exposure, adopting sustainable land-use practices, and advancing urban planning, have shown promise in lowering pollution-related health impacts. Public health initiatives, stricter pollution controls, and lifestyle interventions, including antioxidant-rich diets, can also mitigate risks. Pollution remains preventable, as demonstrated by high-income nations implementing cost-effective solutions. Policies like the European Commission's Zero-Pollution Vision aim to reduce pollution to safe levels by 2050, promoting sustainable ecosystems and public health. Addressing soil pollution is critical to combating the global burden of NCDs, particularly CVDs, and fostering a healthier environment for future generations.

Mercury is a significant environmental pollutant and public health threat, primarily recognized for its neurotoxic effects. Increasing evidence also highlights its harmful impact on the cardiovascular system, particularly in adults. Exposure to mercury through contaminated soil, air, or water initiates a cascade of pathological events that lead to organ damage, including platelet activation, oxidative stress, enhanced inflammation, and direct injury to critical cells such as cardiomyocytes and endothelial cells. Endothelial activation triggers the upregulation of adhesion molecules, promoting the recruitment of leukocytes and platelets to vascular sites. These interactions activate both platelets and immune cells, creating a pro-inflammatory, prothrombotic environment. A key outcome is the formation of platelet-leukocyte aggregates (PLAs), which exacerbate thromboinflammation and endothelial dysfunction. These processes significantly elevate cardiovascular risks, including thrombosis and vascular inflammation. This study offers a comprehensive analysis of the mechanisms underlying mercury-induced cardiotoxicity, focusing on oxidative stress, inflammation, and cellular dysfunction. [GRAPHICS] .

Volcanoes, during their explosive and post-explosive phases, as well as through continuous degassing processes, release a range of pollutants hazardous to human health, including toxic gases, fine particulate matter, and heavy metals. These emissions impact over 14% of the global population living in proximity to volcanoes, with effects that can persist for days, decades, or even centuries. Living conditions in these regions often involve chronic exposure to contaminants in the air, water, and soil, significantly increasing the risk of developing neurological disorders. Prolonged exposure to elements such as lead (Pb), mercury (Hg), and cadmium (Cd), among others, results in the accumulation of metals in the brain, which increases oxidative stress and causes neuronal damage and severe neurotoxicity in animals. An examination of metal accumulation in brain cells, particularly astroglia, provides valuable insights into the developmental neurotoxicity of these metals. Moreover, microglia may activate itself to protect from cytotoxicity. In this review, we consider the implications of living near an active volcano for neurotoxicity and the common neurodegenerative diseases. Additionally, we encourage governments to implement public health strategies and mitigation measures to protect vulnerable communities residing near active volcanoes.

Hookworms are soil-transmitted parasitic nematodes that penetrate the host skin before migrating to the lungs. With an estimated 500-700 million people infected worldwide, hookworm infections are a neglected tropical disease and a significant cause of morbidity, particularly in children, pregnant women, and immunocompromised individuals. Although there is ample evidence that complement activation is pivotal to elicit a protective host immune response against invasive pathogens, its role in hookworm infection remains insufficiently explored. Here, we investigated the complement anaphylatoxin, C5a, during the early lung stage of infection with Nippostrongylus brasiliensis in C57BL/6J wild type and C5aR1-/- mice. Despite the previously reported ability of lung larvae to evade complement activation, C5a was detectable locally in lung tissue and bronchoalveolar lavages. Surprisingly, C5aR1 presence directly contributed to the pathogenicity of hookworm infection. The burden of viable parasites in the lungs was mitigated in C5aR1-/- mice, compared to C57BL/6J mice 48 hours post-infection. Additionally, C5aR1-/- mice showed significantly reduced lung injury, lower cytokine release, attenuated alveolar hemorrhage, and limited alveolar-capillary barrier disruption. Neutrophils were the most abundant and highest C5aR1-expressing cell type in the alveolar space after infection. Deficiency of C5aR1 reduced the influx of neutrophils, monocytes, and eosinophils to the pulmonary airways. RNA sequencing of alveolar neutrophils revealed C5aR1-dependent regulation of the novel nuclear protein, DEDD2. In conclusion, our findings highlight the impact of C5aR1 signaling in neutrophils during hookworm infection uncovering an unexpected downside of complement activation in parasitic infection.

Arsenic is one of the toxic metalloid that is ubiquitously distributed in environment that exerts toxic effects by contaminating air, water, soil, and other resources. Groundwater is thought to be the major source of arsenic-induced mammalian toxicity. The current work sheds light on the antioxidant and anti-inflammatory properties of silymarin against arsenic-induced neurotoxicity in rats. Male albino wistar rats were categorized into 4 groups i.e., control, silymarin-treated (50 mg/kg), arsenic-treated (25ppm), and arsenic + silymarin-treated. Arsenic and silymarin were given intragastrically for 28 days. The study found that as compared to the control rats, animals that received arsenic treatment had lower levels of total antioxidants inside their brain tissues. Additionally, a notable rise in malondialdehyde level, protein oxidation, and inflammation was observed in the group of arsenic treatment suggesting oxidative stress generation inside brain tissue of rats leading to neuronal damage. However, silymarin reversed the damage caused by arsenic in rats, demonstrating its anti-inflammatory and antioxidant potential. The electron microscopic and histological results also showed that silymarin reversed the neuronal damage induced by arsenic exposure providing additional evidence of its antioxidative nature. The present study highlights the therapeutic efficacy of silymarin as an antioxidant against arsenic-induced toxicity in rats' brain.

Atrazine (ATR) is a widely used herbicide worldwide that can cause kidney damage in humans and animals by accumulation in water and soil. Lycopene (LYC), a carotenoid with numerous biological activities, plays an important role in kidney protection due to its potent antioxidant and anti-inflammatory effects. The current study sought to investigate the role of interactions between mtDNA and the cGAS-STING signaling pathway in LYC mitigating PANoptosis and inflammation in kidneys induced by ATR exposure. In our research, 350 mice were orally administered LYC (5 mg/kg BW/day) and ATR (50 or 200 mg/kg BW/day) for 21 days. Our results reveal that ATR exposure induces a decrease in mtDNA stability, resulting in the release of mtDNA into the cytoplasm through the mPTP pore and the BAX pore and the mobilization of the cGAS-STING pathway, thereby inducing renal PANoptosis and inflammation. LYC can inhibit the above changes caused by ATR. In conclusion, LYC inhibited ATR exposure-induced histopathological changes, renal PANoptosis, and inflammation by inhibiting the cGAS-STING pathway. Our results demonstrate the positive role of LYC in ATR-induced renal injury and provide a new therapeutic target for treating renal diseases in the clinic.