Measurement of potassium in rats using an In vivo neutron activation analysis system.

Abnormal levels of potassium are linked to several health conditions, including high blood pressure, cardiac dysfunction, kidney damage, and osteoporosis. Given the limited availability of in vivo measurement techniques, there is a need for novel methods to measure potassium to enhance the diagnosis and management of potassium metabolism related diseases. This study aimed to evaluate the feasibility of compact neutron generator based in vivo measurement system for quantification of potassium using rat carcasses. A cohort of thirty-nine rats (n = 20 males and 19 females, average weight 255 ± 15 and 163 ± 7 g) were sacrificed, and their carcasses were placed in polyethylene bottles. The rats were then positioned and irradiated in a carefully designed irradiation cave built alongside the neutron generator with an optimized thermal neutron flux and radiation dose ratio. The irradiation time was 10 min, followed by a 5-min decay and 2-h measurement using a high efficiency high purity germanium detector(HPGe). RESULTS: The average potassium concentration in male and female rats was found to be comparable (male 2874 ± 161 and female 2866 ± 144 µg/g). A marginally positive correlation between potassium concentration and weight was found in female rats only (male(20) = 0.07, P = 0.76 and female r(19) = 0.34, P = 0.15). We assessed the influence of manganese toxicity on potassium levels and observed no significant impact. These results were consistent with our previous study in mice. CONCLUSION: This study suggests that in vivo neutron activation analysis could serve as a promising method to quantify potassium and to investigate the storage and metabolism of potassium in human and in animals.

The challenge and opportunity of gut microbiota-targeted nanomedicine for colorectal cancer therapy.

The gut microbiota is an integral component of the colorectal cancer (CRC) microenvironment and is intimately associated with CRC initiation, progression, and therapeutic outcomes. We reviewed recent advancements in utilizing nanotechnology for modulating gut microbiota, discussing strategies and the mechanisms underlying their design. For future nanomedicine design, we propose a 5I principle for individualized nanomedicine in CRC management.

Dopaminergic Perturbation in the Aetiology of Neurodevelopmental Disorders.

Brain development may be influenced by both genetic and environmental factors, with potential consequences that may last through the lifespan. Alterations during neurogenesis are linked to neurodevelopmental cognitive disorders. Many neurotransmitters and their systems play a vital role in brain development, as most are present prior to synaptogenesis, and they are involved in the aetiology of many neurodevelopmental disorders. For instance, dopamine (DA) receptor expression begins at the early stages of development and matures at adolescence. The long maturation period suggests how important it is for the stabilisation and integration of neural circuits. DA and dopaminergic (DAergic) system perturbations have been implicated in the pathogenesis of several neurological and neuropsychiatric disorders. The DAergic system controls key cognitive and behavioural skills including emotional and motivated behaviour through DA as a neurotransmitter and through the DA neuron projections to major parts of the brain. In this review, we summarise the current understanding of the DAergic system's influence on neurodevelopment and its involvement in the aetiology and progression of major disorders of the developing brain including autism, schizophrenia, attention deficit hyperactivity disorder, down syndrome, and fragile X syndrome.

ALKBH5-mediated N6-methyladenosine modification of HO-1 mRNA regulates ferroptosis in cobalt-induced neurodegenerative damage.

The utilization of Cobalt (Co) has surged due to it is critical role in renewable energy technologies and other high-tech applications. Concurrently, the potential health risks associated with Co exposure have raised concerns. Previous studies, including our own, have shown that Co can impair learn and memory functions as an epigenetic hazard, even at low concentrations. In this study, we explore the mechanisms of Co-induced ferroptosis in neurodegenerative damage both in vivo and in vitro, focusing on the epigenetic regulation by N6-methyladenosine (m6A) demethylase alkB homolog 5 (ALKBH5). We identify heme oxygenase-1 (HO-1) as a direct target gene of ALKBH5, playing a crucial role in mitigating Co-induced ferroptosis. ALKBH5 deficiency affects the post-transcriptional regulation of HO-1 through m6A modification, which in turn influences mRNA's stability, intracellular distribution, and alternative splicing, thereby enhancing susceptibility to Co-induced ferroptosis. Additionally, we discuss the potential involvement of heterogeneous nuclear ribonucleoprotein M (hnRNPM) in regulating alternative splicing of HO-1 mRNA, potentially mediated by m6A modifications. This study provides new epigenetic insights into the post-transcriptional regulatory mechanisms involved in Co-induced ferroptosis and highlights the broader implications of environmental hazards in neurodegenerative damage.

JAK2/STAT3 signaling pathway mediates methylmercury toxicity in mouse astrocyte neuronal C8-D1A cell line.

Methylmercury (MeHg) is an environmental pollutant. Consumption of contaminated fish is the main exposure route in humans, leading to severe neurological disorders. Upon ingestion MeHg reaches the brain and selectively accumulates in astrocytes disrupting glutamate and calcium homeostasis and increasing oxidative stress. Despite extensive research, the molecular mechanisms underlying MeHg neurotoxicity remain incompletely understood. The induction of nuclear factor erythroid 2-related factor 2 (Nrf2) and its role activating antioxidant responses during MeHg-induced oxidative injury have garnered significant attention as a potential therapeutic target against MeHg toxicity. However, recent studies indicate that the Nrf2 signaling pathway alone may not be sufficient to mitigate MeHg-induced damage, suggesting the existence of other protective mechanisms. The signal transducer and activator of transcription 3 (STAT3) plays a crucial role in cell growth and survival. Several studies have also highlighted its involvement in regulating redox homeostasis, thereby preventing oxidative stress through mechanisms that involve modulation of nuclear genes that encode electron transport complexes (ETC) and antioxidant enzymes. These characteristics suggest that STAT3 could serve as a viable mechanism to mitigate MeHg toxicity, either in conjunction with or as an alternative to Nrf2 signaling. Our previous findings demonstrated that MeHg activates the STAT3 signaling pathway in the GT1-7 hypothalamic neuronal cell line, suggesting its potential role in promoting neuroprotection. Here, to elucidate the role of the STAT3 signaling pathway in MeHg neurotoxicity, we pharmacologically inhibited STAT3 using AG490 in the C8D1A astrocytic cell line exposed to 10 µM MeHg. Our data demonstrated that pharmacological inhibition of STAT3 phosphorylation exacerbates MeHg-induced mortality, antioxidant responses, and ROS production, suggesting that STAT3 may contribute to neuroprotection against MeHg exposure in astrocytes.

Copper-mediated neurotoxicity and genetic vulnerability in the background of neurodegenerative diseases in C. elegans.

The mechanisms associated with neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD) have yet to be fully characterized, and genetic as well as environmental factors in their disease etiology are under appreciated. While mutations in genes such as PARKIN and LRRK2 have been linked to PD, the idiopathic component of the disease suggests a contribution of environmental risk factors, including metals, such as copper (Cu). Cu overexposure has been reported to cause oxidative stress and neurotoxicity, but its role in neurodegenerative diseases is rarely studied. Using Caenorhabditis elegans (C. elegans) as a model organism for neurotoxicity, we assessed the effects of Cu oversupply in AD and PD models. Our findings reveal that while copper treatment did not induce neurodegeneration in wildtype worms or the AD model, it significantly exacerbated neurodegeneration in the PD-associated mutants PARKIN and LRRK2. These results suggest that genetic predisposition for PD enhances the sensitivity to copper toxicity, highlighting the multifactorial nature of neurodegenerative diseases. Furthermore, our study provides insight into the mechanisms underlying Cu-induced neurotoxicity in PD models, including disruptions in dopamine levels, altered dopamine-dependent behavior and degraded dopaminergic neurons. Overall, our novel findings contribute to a better understanding of the complex interactions between genetic susceptibility, environmental factors, and neurodegenerative disease pathogenesis, emphasizing the importance of a tightly regulated Cu homeostasis in the etiology of PD.

Trends of hair Hg accumulation in reproductive-age women living in Central Russia and the calculated costs of Hg-induced IQ loss in the period between 2005 and 2021.

The objective of the present study was to retrospectively evaluate hair mercury (Hg) content in reproductive-age women living in Central Russia (Moscow and Moscow region), and to calculate the potential costs of the potential Hg-induced IQ loss in a hypothetical national birth cohort. MATERIALS AND METHODS: A total of 36,263 occupationally non-exposed women aged between 20 and 40 years living in Moscow (n = 30,626) or Moscow region (n = 5637) in the period between 2005 and 2021 participated in this study. Hair Hg content was evaluated with inductively coupled plasma-mass spectrometry (ICP-MS). Hair Hg levels in reproductive-age women were used for assessment of the potential IQ loss and its costs. RESULTS: The results demonstrate that hair Hg content in the periods between 2010 and 2015, and 2016-2021 was significantly lower than that in 2005-2009 by 26 % and 51 %, respectively. The highest hair Hg level was observed in women in 2005 (0.855 µg/g), being more than 2.5-fold higher than the lowest value observed in 2020 (0.328 µg/g). Multiple regression analysis revealed a significant inverse association between the year of analysis and hair Hg content (ß = -0.288; p < 0.001). The calculations demonstrate that in 2005 the costs of IQ loss in children exceeded 1.0 (1.6) billion USD, whereas in 2020 the costs of IQ loss accounted to approximately 0.15 (0.28) billion USD. CONCLUSION: Taken together, our data demonstrate that Hg accumulation in reproductive-age women reduced significantly in Russia from 2005 to 2021 resulting in predicted economic benefits by decreasing the costs of Hg-induced IQ loss.

Heavy Metal Interactions with Neuroglia and Gut Microbiota: Implications for Huntington's Disease.

Huntington's disease (HD) is a rare but progressive and devastating neurodegenerative disease characterized by involuntary movements, cognitive decline, executive dysfunction, and neuropsychiatric conditions such as anxiety and depression. It follows an autosomal dominant inheritance pattern. Thus, a child who has a parent with the mutated huntingtin (mHTT) gene has a 50% chance of developing the disease. Since the HTT protein is involved in many critical cellular processes, including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, and autophagy, its aberrant aggregates lead to the disruption of numerous cellular pathways and neurodegeneration. Essential heavy metals are vital at low concentrations; however, at higher concentrations, they can exacerbate HD by disrupting glial-neuronal communication and/or causing dysbiosis (disturbance in the gut microbiota, GM), both of which can lead to neuroinflammation and further neurodegeneration. Here, we discuss in detail the interactions of iron, manganese, and copper with glial-neuron communication and GM and indicate how this knowledge may pave the way for the development of a new generation of disease-modifying therapies in HD.

The Role of Gut Microbiota in the Neuroprotective Effects of Selenium in Alzheimer's Disease.

The objective of the present review was to provide a timely update on the molecular mechanisms underlying the beneficial role of Se in Alzheimer's disease pathogenesis, and discuss the potential role of gut microbiota modulation in this neuroprotective effect. The existing data demonstrate that selenoproteins P, M, S, R, as well as glutathione peroxidases and thioredoxin reductases are involved in regulation of Aß formation and aggregation, tau phosphorylation and neurofibrillary tangles formation, as well as mitigate the neurotoxic effects of Aß and phospho-tau. Correspondingly, supplementation with various forms of Se in cellular and animal models of AD was shown to reduce Aß formation, tau phosphorylation, reverse the decline in brain antioxidant levels, inhibit neuronal oxidative stress and proinflammatory cytokine production, improve synaptic plasticity and neurogenesis, altogether resulting in improved cognitive functions. In addition, most recent findings demonstrate that these neuroprotective effects are associated with Se-induced modulation of gut microbiota. In animal models of AD, Se supplementation was shown to improve gut microbiota biodiversity with a trend to increased relative abundance of Lactobacillus, Bifidobacterium, and Desulfivibrio, while reducing that of Lachnospiracea_NK4A136, Rikenella, and Helicobacter. Moreover, the relative abundance of Se-affected taxa was significantly associated with Aß accumulation, tau phosphorylation, neuronal oxidative stress, and neuroinflammation, indicative of the potential role of gut microbiota to mediate the neuroprotective effects of Se in AD. Hypothetically, modulation of gut microbiota along with Se supplementation may improve the efficiency of the latter in AD, although further detailed laboratory and clinical studies are required.

Epigenetic Mechanisms of Aluminum-Induced Neurotoxicity and Alzheimer's Disease: A Focus on Non-Coding RNAs.

Aluminum (Al) is known to induce neurotoxic effects, potentially contributing to Alzheimer's disease (AD) pathogenesis. Recent studies suggest that epigenetic modification may contribute to Al neurotoxicity, although the mechanisms are still debatable. Therefore, the objective of the present study was to summarize existing data on the involvement of epigenetic mechanisms in Al-induced neurotoxicity, especially AD-type pathology. Existing data demonstrate that Al exposure induces disruption in DNA methylation, histone modifications, and non-coding RNA expression in brains. Alterations in DNA methylation following Al exposure were shown to be mediated by changes in expression and activity of DNA methyltransferases (DNMTs) and ten-eleven translocation proteins (TETs). Al exposure was shown to reduce histone acetylation by up-regulating expression of histone deacetylases (HDACs) and impair histone methylation, ultimately contributing to down-regulation of brain-derived neurotrophic factor (BDNF) expression and activation of nuclear factor κB (NF-κB) signaling. Neurotoxic effects of Al exposure were also associated with aberrant expression of non-coding RNAs, especially microRNAs (miR). Al-induced patterns of miR expression were involved in development of AD-type pathology by increasing amyloid ß (Aß) production through up-regulation of Aß precursor protein (APP) and ß secretase (BACE1) expression (down-regulation of miR-29a/b, miR-101, miR-124, and Let-7c expression), increasing in neuroinflammation through NF-κB signaling (up-regulation of miR-9, miR-125b, miR-128, and 146a), as well as modulating other signaling pathways. Furthermore, reduced global DNA methylation, altered histone modification, and aberrant miRNA expression were associated with cognitive decline in Al-exposed subjects. However, further studies are required to evaluate the contribution of epigenetic mechanisms to Al-induced neurotoxicity and/or AD development.

S-allyl-cysteine triggers cytotoxic events in rat glioblastoma RG2 and C6 cells and improves the effect of temozolomide through the regulation of oxidative responses.

Glioblastoma (GBM) is an aggressive form of cancer affecting the Central Nervous System (CNS) of thousands of people every year. Redox alterations have been shown to play a key role in the development and progression of these tumors as Reactive Oxygen Species (ROS) formation is involved in the modulation of several signaling pathways, transcription factors, and cytokine formation. The second-generation oral alkylating agent temozolomide (TMZ) is the first-line chemotherapeutic drug used to treat of GBM, though patients often develop primary and secondary resistance, reducing its efficacy. Antioxidants represent promising and potential coadjutant agents as they can reduce excessive ROS formation derived from chemo- and radiotherapy, while decreasing pharmacological resistance. S-allyl-cysteine (SAC) has been shown to inhibit the proliferation of several types of cancer cells, though its precise antiproliferative mechanisms remain poorly investigated. To date, SAC effects have been poorly explored in GBM cells. Here, we investigated the effects of SAC in vitro, either alone or in combination with TMZ, on several toxic and modulatory endpoints-including oxidative stress markers and transcriptional regulation-in two glioblastoma cell lines from rats, RG2 and C6, to elucidate some of the biochemical and cellular mechanisms underlying its antiproliferative properties. SAC (1-750 µM) decreased cell viability in both cell lines in a concentration-dependent manner, although C6 cells were more resistant to SAC at several of the tested concentrations. TMZ also produced a concentration-dependent effect, decreasing cell viability of both cell lines. In combination, SAC (1 µM or 100 µM) and TMZ (500 µM) enhanced the effects of each other. SAC also augmented the lipoperoxidative effect of TMZ and reduced cell antioxidant resistance in both cell lines by decreasing the TMZ-induced increase in the GSH/GSSG ratio. In RG2 and C6 cells, SAC per se had no effect on Nrf2/ARE binding activity, while in RG2 cells TMZ and the combination of SAC + TMZ decreased this activity. Our results demonstrate that SAC, alone or in combination with TMZ, exerts antitumor effects mediated by regulatory mechanisms of redox activity responses. SAC is also a safe drug for testing in other models as it produces non-toxic effects in primary astrocytes. Combined, these effects suggest that SAC affords antioxidant properties and potential antitumor efficacy against GBM.

Ferroptosis as an emerging target in sickle cell disease.

Sickle cell disease (SCD) is an inherited hemoglobin disorder marked by red blood cell sickling, resulting in severe anemia, painful episodes, extensive organ damage, and shortened life expectancy. In SCD, increased iron levels can trigger ferroptosis, a specific type of cell death characterized by reactive oxygen species (ROS) and lipid peroxide accumulation, leading to damage and organ impairments. The intricate interplay between iron, ferroptosis, inflammation, and oxidative stress in SCD underscores the necessity of thoroughly understanding these processes for the development of innovative therapeutic strategies. This review highlights the importance of balancing the complex interactions among various factors and exploitation of the knowledge in developing novel therapeutics for this devastating disease.

Microglial Sp1 induced LRRK2 upregulation in response to manganese exposure, and 17ß-estradiol afforded protection against this manganese toxicity.

Chronic exposure to elevated levels of manganese (Mn) causes a neurological disorder referred to as manganism, presenting symptoms similar to those of Parkinson's disease (PD), yet the mechanisms by which Mn induces its neurotoxicity are not completely understood. 17ß-estradiol (E2) affords neuroprotection against Mn toxicity in various neural cell types including microglia. Our previous studies have shown that leucine-rich repeat kinase 2 (LRRK2) mediates Mn-induced inflammatory toxicity in microglia. The LRRK2 promoter sequences contain three putative binding sites of the transcription factor (TF), specificity protein 1 (Sp1), which increases LRRK2 promoter activity. In the present study, we tested if the Sp1-LRRK2 pathway plays a role in both Mn toxicity and the protection afforded by E2 against Mn toxicity in BV2 microglial cells. The results showed that Mn induced cytotoxicity, oxidative stress, and tumor necrosis factor-α production, which were attenuated by an LRRK2 inhibitor, GSK2578215A. The overexpression of Sp1 increased LRRK2 promoter activity, mRNA and protein levels, while inhibition of Sp1 with its pharmacological inhibitor, mithramycin A, attenuated the Mn-induced increases in LRRK2 expression. Furthermore, E2 attenuated the Mn-induced Sp1 expression by decreasing the expression of Sp1 via the promotion of the ubiquitin-dependent degradation pathway, which was accompanied by increased protein levels of RING finger protein 4, the E3-ligase of Sp1, Sp1 ubiquitination, and SUMOylation. Taken together, our novel findings suggest that Sp1 serves as a critical TF in Mn-induced LRRK2 expression as well as in the protection afforded by E2 against Mn toxicity through reduction of LRRK2 expression in microglia.

Therapeutic Potential of Fingolimod on Psychological Symptoms and Cognitive Function in Neuropsychiatric and Neurological Disorders.

Neuropsychiatric and neurological disorders pose a significant global health burden, highlighting the need for innovative therapeutic approaches. Fingolimod (FTY720), a common drug to treat multiple sclerosis, has shown promising efficacy against various neuropsychiatric and neurological disorders. Fingolimod exerts its neuroprotective effects by targeting multiple cellular and molecular processes, such as apoptosis, oxidative stress, neuroinflammation, and autophagy. By modulating Sphingosine-1-Phosphate Receptor activity, a key regulator of immune cell trafficking and neuronal function, it also affects synaptic activity and strengthens memory formation. In the hippocampus, fingolimod decreases glutamate levels and increases GABA levels, suggesting a potential role in modulating synaptic transmission and neuronal excitability. Taken together, fingolimod has emerged as a promising neuroprotective agent for neuropsychiatric and neurological disorders. Its broad spectrum of cellular and molecular effects, including the modulation of apoptosis, oxidative stress, neuroinflammation, autophagy, and synaptic plasticity, provides a comprehensive therapeutic approach for these debilitating conditions. Further research is warranted to fully elucidate the mechanisms of action of fingolimod and optimize its use in the treatment of neuropsychiatric and neurological disorders.

Carcinogenic Risk from Lead and Cadmium Contaminating Cow Milk and Soya Beverage Brands Available in the Portuguese Market.

Our previous work demonstrated the presence of lead (Pb) and cadmium (Cd) contamination in cow milk (CM) and soy beverages (SBs) in Portugal. These metals share carcinogenic mechanisms, suggesting at least additive effects. Our goals were to assess carcinogenic risks from Pb and Cd intake detected in various CM and SB brands on the Portuguese market and to determine the relative contributions of Pb and Cd. Furthermore, we modeled different consumption scenarios for various age/body weight groups to estimate cumulative Excess Lifetime Carcinogenic Risk (ELCR). ELCR was computed by multiplying chronic daily intake by a cancer slope factor for each metal, with an ELCR > 1 × 10-4 indicating carcinogenic risk. Five CM and three SB brands posed cancer risks in children, with the highest values at 1.75 × 10-4 and 9.12 × 10-5, respectively; Pb had mean relative contributions of 87.8 ± 3.1% in CM and 54.9 ± 12.1% in SB. Carcinogenic risks were observed for children, adolescents, and adults in several CM or SB consumption scenarios, albeit at levels above typical Portuguese intakes. Strict monitoring of metal levels, such as Pb and Cd, is advised because CM is a component of many foods, including baby food.

Therapeutic potential of Phycocyanin in gastrointestinal cancers and related disorders.

Gastrointestinal cancer is the most fatal cancer worldwide. The etiology of gastrointestinal cancer has yet to be fully characterized. Alcohol consumption, obesity, tobacco, Helicobacter pylori and gastrointestinal disorders, including gastroesophageal reflux disease, gastric ulcer, colon polyps and non-alcoholic fatty liver disease are among the several risks factors for gastrointestinal cancers. Phycocyanin which is abundant in Spirulina. Phycocyanin, a member of phycobiliprotein family with intense blue color, is an anti-diabetic, neuroprotective, anti-oxidative, anti-inflammatory, and anticancer compound. Evidence exists supporting that phycocyanin has antitumor effects, exerting its pharmacological effects by targeting a variety of cellular and molecular processes, i.e., apoptosis, cell-cycle arrest, migration and Wnt/ß-catenin signaling. Phycocyanin has also been applied in treatment of several gastrointestinal disorders such as, gastric ulcer, ulcerative colitis and fatty liver that is known as a risk factor for progression to cancer. Herein, we summarize various cellular and molecular pathways that are affected by phycocyanin, its efficacy upon combined drug treatment, and the potential for nanotechnology in its gastrointestinal cancer therapy.

Treatment of manganese and lead poisoning with sodium para-aminosalicylic acid: A contemporary update.

Sodium para-aminosalicylic acid (PAS-Na) treatment for manganese (Mn) intoxication has shown efficacy in experimental and clinical studies, giving rise to additional studies on its efficacy for lead (Pb) neurotoxicity and its associated mechanisms of neuroprotection. The difference between PAS-Na and other metal complexing agents, such as edetate calcium sodium (CaNa2-EDTA), is firstly that PAS-Na can readily pass through the blood-brain barrier (BBB), and complex and facilitate the excretion of manganese and lead. Secondly, PAS-Na has anti-inflammatory effects. Recent studies have broadened the understanding on the mechanisms associated with efficacy of PAS-Na. The latter has been shown to modulate multifarious manganese- and lead- induced neurotoxicity, via its anti-apoptotic and anti-inflammatory effects, as well as its ability to inhibit pyroptosis, and regulate abnormal autophagic processes. These observations provide novel scientific bases and new concepts for the treatment of lead, mercury, copper, thallium, as well as other toxic encephalopathies, and implicate PAS-Na as a compound with greater prospects for clinical medical application.

Molecular mechanisms of environmental pollutant-induced cartilage damage: from developmental disorders to osteoarthritis.

The objective of the present study was to review the molecular mechanisms of the adverse effects of environmental pollutants on chondrocytes and extracellular matrix (ECM). Existing data demonstrate that both heavy metals, including cadmium (Cd), lead (Pb), and arsenic (As), as well as organic pollutants, including polychlorinated dioxins and furans (PCDD/Fs) and polychlorinated biphenyls (PCB), bisphenol A, phthalates, polycyclic aromatic hydrocarbons (PAH), pesticides, and certain other organic pollutants that target cartilage ontogeny and functioning. Overall, environmental pollutants reduce chondrocyte viability through the induction apoptosis, senescence, and inflammatory response, resulting in cell death and impaired ECM production. The effects of organic pollutants on chondrocyte development and viability were shown to be mediated by binding to the aryl hydrocarbon receptor (AhR) signaling and modulation of non-coding RNA expression. Adverse effects of pollutant exposures were observed in articular and growth plate chondrocytes. These mechanisms also damage chondrocyte precursors and subsequently hinder cartilage development. In addition, pollutant exposure was shown to impair chondrogenesis by inhibiting the expression of Sox9 and other regulators. Along with altered Runx2 signaling, these effects also contribute to impaired chondrocyte hypertrophy and chondrocyte-to-osteoblast trans-differentiation, resulting in altered endochondral ossification. Several organic pollutants including PCDD/Fs, PCBs and PAHs, were shown to induce transgenerational adverse effects on cartilage development and the resulting skeletal deformities. Despite of epidemiological evidence linking human environmental pollutant exposure to osteoarthritis or other cartilage pathologies, the data on the molecular mechanisms of adverse effects of environmental pollutant exposure on cartilage tissue were obtained from studies in laboratory rodents, fish, or cell cultures and should be carefully extrapolated to humans, although they clearly demonstrate that cartilage should be considered a putative target for environmental pollutant toxicity.