scholarly journals Glyphosate Herbicide: Reproductive Outcomes and Multigenerational Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
María Mercedes Milesi ◽  
Virginia Lorenz ◽  
Milena Durando ◽  
María Florencia Rossetti ◽  
Jorgelina Varayoud
Keyword(s):  
Endocrine Function ◽  
Social Concern ◽  
Long Term Effects ◽  
Crop Varieties ◽  
Estrogenic Effects ◽  
Multigenerational Effects ◽  
Successive Generations

Glyphosate base herbicides (GBHs) are the most widely applied pesticides in the world and are mainly used in association with GBH-tolerant crop varieties. Indiscriminate and negligent use of GBHs has promoted the emergence of glyphosate resistant weeds, and consequently the rise in the use of these herbicides. Glyphosate, the active ingredient of all GBHs, is combined with other chemicals known as co-formulants that enhance the herbicide action. Nowadays, the safety of glyphosate and its formulations remain to be a controversial issue, as evidence is not conclusive whether the adverse effects are caused by GBH or glyphosate, and little is known about the contribution of co-formulants to the toxicity of herbicides. Currently, alarmingly increased levels of glyphosate have been detected in different environmental matrixes and in foodstuff, becoming an issue of social concern. Some in vitro and in vivo studies have shown that glyphosate and its formulations exhibit estrogen-like properties, and growing evidence has indicated they may disrupt normal endocrine function, with adverse consequences for reproductive health. Moreover, multigenerational effects have been reported and epigenetic mechanisms have been proved to be involved in the alterations induced by the herbicide. In this review, we provide an overview of: i) the routes and levels of human exposure to GBHs, ii) the potential estrogenic effects of glyphosate and GBHs in cell culture and animal models, iii) their long-term effects on female fertility and mechanisms of action, and iv) the consequences on health of successive generations.

scholarly journals Metformin decreases hyaluronan synthesis by vascular smooth muscle cells

2019 ◽  
Vol 68 (2) ◽  
pp. 383-391 ◽  
Author(s):  
Annele Sainio ◽  
Piia Takabe ◽  
Sanna Oikari ◽  
Henriikka Salomäki-Myftari ◽  
Markku Koulu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Response To Treatment ◽  
Long Term Effects

Metformin is the first-line drug in the treatment of type 2 diabetes worldwide based on its effectiveness and cardiovascular safety. Currently metformin is increasingly used during pregnancy in women with gestational diabetes mellitus, even if the long-term effects of metformin on offspring are not exactly known. We have previously shown that high glucose concentration increases hyaluronan (HA) production of cultured human vascular smooth muscle cells (VSMC) via stimulating the expression of hyaluronan synthase 2 (HAS2). This offers a potential mechanism whereby hyperglycemia leads to vascular macroangiopathy. In this study, we examined whether gestational metformin use affects HA content in the aortic wall of mouse offspring in vivo. We also examined the effect of metformin on HA synthesis by cultured human VSMCs in vitro. We found that gestational metformin use significantly decreased HA content in the intima-media of mouse offspring aortas. In accordance with this, the synthesis of HA by VSMCs was also significantly decreased in response to treatment with metformin. This decrease in HA synthesis was shown to be due to the reduction of both the expression of HAS2 and the amount of HAS substrates, particularly UDP-N-acetylglucosamine. As shown here, gestational metformin use is capable to program reduced HA content in the vascular wall of the offspring strongly supporting the idea, that metformin possesses long-term vasculoprotective effects.

scholarly journals Long-term nicotine exposure dampens LPS-induced nerve-mediated airway hyperreactivity in murine airways

2017 ◽  
Vol 313 (3) ◽  
pp. L516-L523 ◽  
Author(s):  
Yuan Xu ◽  
Lars-Olaf Cardell
Keyword(s):  
Airway Hyperreactivity ◽  
Nicotine Exposure ◽  
Long Term Effects ◽  
Contractile Responses ◽  
Neuronal Mechanisms ◽  
Airway Infections ◽  
Before And After

Nicotine is a major component of cigarette smoke. It causes addiction and is used clinically to aid smoke cessation. The aim of the present study is to investigate the effect of nicotine on lipopolysaccharide (LPS)-induced airway hyperreactivity (AHR) and to explore the potential involvement of neuronal mechanisms behind nicotine’s effects in murine models in vivo and in vitro. BALB/c mice were exposed to nicotine in vivo via subcutaneous Alzet osmotic minipumps containing nicotine tartate salt solution (24 mg·kg−1·day−1) for 28 days. LPS (0.1 mg/ml, 20 µl) was administered intranasally for 3 consecutive days during the end of this period. Lung functions were measured with flexiVent. For the in vitro experiments, mice tracheae were organcultured with either nicotine (10 μM) or vehicle (DMSO, 0.1%) for 4 days. Contractile responses of the tracheal segments were measured in myographs following electric field stimulation (EFS; increasing frequencies of 0.2 to 12.8 Hz) before and after incubation with 10 µg/ml LPS for 1 h. Results showed that LPS induced AHR to methacholine in vivo and increased contractile responses to EFS in vitro. Interestingly, long-term nicotine exposure markedly dampened this LPS-induced AHR both in vitro and in vivo. Tetrodotoxin (TTX) inhibited LPS-induced AHR but did not further inhibit nicotine-suppressed AHR in vivo. In conclusion, long-term nicotine exposure dampened LPS-induced AHR. The effect of nicotine was mimicked by TTX, suggesting the involvement of neuronal mechanisms. This information might be used for evaluating the long-term effects of nicotine and further exploring of how tobacco products interact with bacterial airway infections.

scholarly journals Lactobacillus acidophilus stimulates the expression of SLC26A3 via a transcriptional mechanism

2010 ◽  
Vol 298 (3) ◽  
pp. G395-G401 ◽  
Author(s):  
Geetu Raheja ◽  
Varsha Singh ◽  
Ke Ma ◽  
Redouane Boumendjel ◽  
Alip Borthakur ◽  
...  
Keyword(s):  
Western Blot ◽  
Lactobacillus Acidophilus ◽  
Promoter Activity ◽  
In Vivo Studies ◽  
Mrna Levels ◽  
Long Term Effects ◽  
Exchange Activity

Clinical efficacy of probiotics in treating various forms of diarrhea has been clearly established. However, mechanisms underlying antidiarrheal effects of probiotics are not completely defined. Diarrhea is caused either by decreased absorption or increased secretion of electrolytes and solutes in the intestine. In this regard, the electroneutral absorption of two major electrolytes, Na+ and Cl−, occurs mainly through the coupled operation of Na+/H+ exchangers and Cl−/OH− exchangers. Previous studies from our laboratory have shown that Lactobacillus acidophilus (LA) acutely stimulated Cl−/OH− exchange activity via an increase in the surface levels of the apical anion exchanger SLC26A3 (DRA). However, whether probiotics influence SLC26A3 expression and promoter activity has not been examined. The present studies were, therefore, undertaken to investigate the long-term effects of LA on SLC26A3 expression and promoter activity. Treatment of Caco-2 cells with LA for 6–24 h resulted in a significant increase in Cl−/OH− exchange activity. DRA mRNA levels were also significantly elevated in response to LA treatment starting as early as 8 h. Additionally, the promoter activity of DRA was increased by more than twofold following 8 h LA treatment of Caco-2 cells. Similar to the in vitro studies, in vivo studies using mice gavaged with LA also showed significantly increased DRA mRNA (∼4-fold) and protein expression in the colonic regions as assessed by Western blot analysis and immunofluorescence. In conclusion, increase in DRA promoter activity and expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of LA.

scholarly journals Bisphenols as Environmental Triggers of Thyroid Dysfunction: Clues and Evidence

2020 ◽  
Vol 17 (8) ◽  
pp. 2654 ◽  
Author(s):  
Francesca Gorini ◽  
Elisa Bustaffa ◽  
Alessio Coi ◽  
Giorgio Iervasi ◽  
Fabrizio Bianchi
Keyword(s):  
Thyroid Dysfunction ◽  
Direct Action ◽  
Epidemiological Studies ◽  
In Vivo Studies ◽  
Original Research ◽  
Long Term Effects ◽  
Toxicological Studies

Bisphenols (BPs), and especially bisphenol A (BPA), are known endocrine disruptors (EDCs), capable of interfering with estrogen and androgen activities, as well as being suspected of other health outcomes. Given the crucial role of thyroid hormones and the increasing incidence of thyroid carcinoma in the last few decades, this review analyzes the effects of BPS on the thyroid, considering original research in vitro, in vivo, and in humans published from January 2000 to October 2019. Both in vitro and in vivo studies reported the ability of BPs to disrupt thyroid function through multiple mechanisms. The antagonism with thyroid receptors (TRs), which affects TR-mediated transcriptional activity, the direct action of BPs on gene expression at the thyroid and the pituitary level, the competitive binding with thyroid transport proteins, and the induction of toxicity in several cell lines are likely the main mechanisms leading to thyroid dysfunction. In humans, results are more contradictory, though some evidence suggests the potential of BPs in increasing the risk of thyroid nodules. A standardized methodology in toxicological studies and prospective epidemiological studies with individual exposure assessments are warranted to evaluate the pathophysiology resulting in the damage and to establish the temporal relationship between markers of exposure and long-term effects.

scholarly journals Long-Term Deleterious Effects of Short-term Hyperoxia on Cancer Progression—Is Brain-Derived Neurotrophic Factor an Important Mediator? An Experimental Study

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 688
Author(s):  
Adrian Tiron ◽  
Irina Ristescu ◽  
Paula A. Postu ◽  
Crina E. Tiron ◽  
Florin Zugun-Eloae ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Long Term Effects ◽  
Short Term ◽  
Bdnf Expression ◽  
In Vivo Models

Perioperative factors promoting cancer recurrence and metastasis are under scrutiny. While oxygen toxicity is documented in several acute circumstances, its implication in tumor evolution is poorly understood. We investigated hyperoxia long-term effects on cancer progression and some underlying mechanisms using both in vitro and in vivo models of triple negative breast cancer (TNBC). We hypothesized that high oxygen exposure, even of short duration, may have long-term effects on cancer growth. Considering that hyperoxic exposure results in reactive oxygen species (ROS) formation, increased oxidative stress and increased Brain-Derived Neurotrophic Factor (BDNF) expression, BDNF may mediate hyperoxia effects offering cancer cells a survival advantage by increased angiogenesis and epithelial mesenchymal transition (EMT). Human breast epithelial MCF10A, human MDA-MB-231 and murine 4T1 TNBC were investigated in 2D in vitro system. Cells were exposed to normoxia or hyperoxia (40%, 60%, 80% O2) for 6 h. We evaluated ROS levels, cell viability and the expression of BDNF, HIF-1α, VEGF-R2, Vimentin and E-Cadherin by immunofluorescence. The in vivo model consisted of 4T1 inoculation in Balb/c mice and tumor resection 2 weeks after and 6 h exposure to normoxia or hyperoxia (40%, 80% O2). We measured lung metastases and the same molecular markers, immediately and 4 weeks after surgery. The in vitro study showed that short-term hyperoxia exposure (80% O2) of TNBC cells increases ROS, increases BDNF expression and that promotes EMT and angiogenesis. The in vivo data indicates that perioperative hyperoxia enhances metastatic disease and this effect could be BDNF mediated.

scholarly journals An updated overview of e-cigarette impact on human health

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Patrice Marques ◽  
Laura Piqueras ◽  
Maria-Jesus Sanz
Keyword(s):  
Human Health ◽  
Tobacco Consumption ◽  
Heating Process ◽  
Long Term Effects ◽  
Safe Alternative ◽  
The Impact ◽  
Harmful Effects

AbstractThe electronic cigarette (e-cigarette), for many considered as a safe alternative to conventional cigarettes, has revolutionised the tobacco industry in the last decades. In e-cigarettes, tobacco combustion is replaced by e-liquid heating, leading some manufacturers to propose that e-cigarettes have less harmful respiratory effects than tobacco consumption. Other innovative features such as the adjustment of nicotine content and the choice of pleasant flavours have won over many users. Nevertheless, the safety of e-cigarette consumption and its potential as a smoking cessation method remain controversial due to limited evidence. Moreover, it has been reported that the heating process itself can lead to the formation of new decomposition compounds of questionable toxicity. Numerous in vivo and in vitro studies have been performed to better understand the impact of these new inhalable compounds on human health. Results of toxicological analyses suggest that e-cigarettes can be safer than conventional cigarettes, although harmful effects from short-term e-cigarette use have been described. Worryingly, the potential long-term effects of e-cigarette consumption have been scarcely investigated. In this review, we take stock of the main findings in this field and their consequences for human health including coronavirus disease 2019 (COVID-19).

scholarly journals Cold-Inducible RNA-Binding Protein but Not Its Antisense lncRNA Is a Direct Negative Regulator of Angiogenesis In Vitro and In Vivo via Regulation of the 14q32 angiomiRs—Mi-croRNA-329-3p and microRNA-495-3p

2021 ◽  
Vol 22 (23) ◽  
pp. 12678
Author(s):  
Eveline A. C. Goossens ◽  
Licheng Zhang ◽  
Margreet R. de Vries ◽  
J. Wouter Jukema ◽  
Paul H. A. Quax ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Tube Formation ◽  
Negative Regulator ◽  
Long Term Effects

Inhibition of the 14q32 microRNAs, miR-329-3p and miR-495-3p, improves post-ischemic neovascularization. Cold-inducible RNA-binding protein (CIRBP) facilitates maturation of these microRNAs. We hypothesized that CIRBP deficiency improves post-ischemic angiogenesis via downregulation of 14q32 microRNA expression. We investigated these regulatory mechanisms both in vitro and in vivo. We induced hindlimb ischemia in Cirp−/− and C57Bl/6-J mice, monitored blood flow recovery with laser Doppler perfusion imaging, and assessed neovascularization via immunohistochemistry. Post-ischemic angiogenesis was enhanced in Cirp−/− mice by 34.3% with no effects on arteriogenesis. In vivo at day 7, miR-329-3p and miR-495-3p expression were downregulated in Cirp−/− mice by 40.6% and 36.2%. In HUVECs, CIRBP expression was upregulated under hypothermia, while miR-329-3p and miR-495-3p expression remained unaffected. siRNA-mediated CIRBP knockdown led to the downregulation of CIRBP-splice-variant-1 (CIRBP-SV1), CIRBP antisense long noncoding RNA (lncRNA-CIRBP-AS1), and miR-495-3p with no effects on the expression of CIRBP-SV2-4 or miR-329-3p. siRNA-mediated CIRBP knockdown improved HUVEC migration and tube formation. SiRNA-mediated lncRNA-CIRBP-AS1 knockdown had similar long-term effects. After short incubation times, however, only CIRBP knockdown affected angiogenesis, indicating that the effects of lncRNA-CIRBP-AS1 knockdown were secondary to CIRBP-SV1 downregulation. CIRBP is a negative regulator of angiogenesis in vitro and in vivo and acts, at least in part, through the regulation of miR-329-3p and miR-495-3p.

scholarly journals Analysis of gene transcription alterations at the blastocyst stage related to the long-term consequences of in vitro culture in mice

Reproduction ◽  
2009 ◽  
Vol 137 (2) ◽  
pp. 271-283 ◽  
Author(s):  
Raúl Fernández-González ◽  
Juan de Dios Hourcade ◽  
Irene López-Vidriero ◽  
Alberto Benguría ◽  
Fernando Rodríguez De Fonseca ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Blastocyst Stage ◽  
Epigenetic Mechanisms ◽  
Long Term Effects ◽  
Long Term Consequences

We have reported thatin vitroculture (IVC) of preimplantation mouse embryos in the presence of FCS produces long-term effects (LTE) on development, growth and behaviour of the offspring at adult age. To analyse the mechanisms underlying this phenomenon, we have examined development and global alterations in gene expression in the mouse blastocysts produced in the presence of FCS, conditions known to be suboptimal and that generate LTE. Embryos culturedin vitroin KSOM and in KSOM+FCS had a reduced number of cells in the inner cell mass at the blastocyst stage compared within vivoderived embryos; however, only culture in KSOM+FCS leads to a reduction in the number of trophoblast cells. Gene expression levels were measured by comparison among three groups of blastocysts (in vivo, IVC in KSOM and IVC in KSOM+FCS). Different patterns of gene expression and development were found between embryos culturedin vitroorin vivo. Moreover, when we compared the embryos produced in KSOM versus KSOM+FCS, we observed that the presence of FCS affected the expression of 198 genes. Metabolism, proliferation, apoptosis and morphogenetic pathways were the most common processes affected by IVC. However, the presence of FCS during IVC preferentially affected genes associated with certain molecular and biological functions related to epigenetic mechanisms. These results suggest that culture-induced alterations in transcription at the blastocyst stage related to epigenetic mechanisms provide a foundation for understanding the molecular origin at the time of preimplantation development of the long-term consequences of IVC in mammals.

scholarly journals Nigella Plants – Traditional Uses, Bioactive Phytoconstituents, Preclinical and Clinical Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Bahare Salehi ◽  
Cristina Quispe ◽  
Muhammad Imran ◽  
Iahtisham Ul-Haq ◽  
Jelena Živković ◽  
...  
Keyword(s):  
Nigella Sativa ◽  
Long Term Effects ◽  
Phytochemical Composition ◽  
Traditional Uses ◽  
The Family ◽  
Omega 6 ◽  
Preclinical And Clinical Studies

Nigella is a small genus of the family Ranunculaceae, which includes some popular species due to their culinary and medicinal properties, especially in Eastern Europe, Middle East, Western, and Central Asia. Therefore, this review covers the traditional uses and phytochemical composition of Nigella and, in particular, Nigella sativa. The pharmacological studies reported in vitro, in vivo, and in humans have also been reviewed. One of the main strength of the use of Nigella is that the seeds are rich in the omega-6 fatty acid linoleic acid and provide an extra-source of dietary phytochemicals, including the bioactive thymoquinone, and characteristics saponins, alkaloids, and flavonoids. Among Nigella species, N. sativa L. is the most studied plant from the genus. Due to the phytochemical composition and pharmacological properties, the seed and seed oil from this plant can be considered as good candidates to formulate functional ingredients on the basis of folklore and scientific knowledge. Nonetheless, the main limations are that more studies, especially, clinical trials are required to standardize the results, e.g. to establish active molecules, dosage, chemical profile, long-term effects and impact of cooking/incorporation into foods.

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