scholarly journals Microcystin Toxicokinetics, Molecular Toxicology, and Pathophysiology in Preclinical Rodent Models and Humans

Toxins ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 537
Author(s):  
Tarana Arman ◽  
John D. Clarke
Keyword(s):  
Current Knowledge ◽  
Covalent Binding ◽  
Daily Intake ◽  
Fecal Excretion ◽  
Rodent Models ◽  
Molecular Toxicology ◽  
Cellular Effects ◽  
Specific Distribution ◽  
Liver And Kidney ◽  
Fish And Shellfish

Microcystins are ubiquitous toxins produced by photoautotrophic cyanobacteria. Human exposures to microcystins occur through the consumption of contaminated drinking water, fish and shellfish, vegetables, and algal dietary supplements and through recreational activities. Microcystin-leucine-arginine (MCLR) is the prototypical microcystin because it is reported to be the most common and toxic variant and is the only microcystin with an established tolerable daily intake of 0.04 µg/kg. Microcystin toxicokinetics is characterized by low intestinal absorption, rapid and specific distribution to the liver, moderate metabolism to glutathione and cysteinyl conjugates, and low urinary and fecal excretion. Molecular toxicology involves covalent binding to and inhibition of protein phosphatases, oxidative stress, cell death (autophagy, apoptosis, necrosis), and cytoskeleton disruption. These molecular and cellular effects are interconnected and are commonly observed together. The main target organs for microcystin toxicity are the intestine, liver, and kidney. Preclinical data indicate microcystins may also have nervous, pulmonary, cardiac, and reproductive system toxicities. Recent evidence suggests that exposure to other hepatotoxic insults could potentiate microcystin toxicity and increase the risk for chronic diseases. This review summarizes the current knowledge for microcystin toxicokinetics, molecular toxicology, and pathophysiology in preclinical rodent models and humans. More research is needed to better understand human toxicokinetics and how multifactorial exposures contribute to disease pathogenesis and progression.

Abstract WP205: Long-chain n-3 Polyunsaturated Fatty Acids Intake and Cardiovascular Disease Mortality Risk in a General Japanese Population: NIPPON DATA80

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Naoko Miyagawa ◽  
Katsuyuki Miura ◽  
Nagako Okuda ◽  
Takashi Kadowaki ◽  
Naoyuki Takashima ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Daily Intake ◽  
Community Dwelling ◽  
Dietary Sodium ◽  
Inverse Association ◽  
Cardiovascular Disease Mortality ◽  
Disease Mortality ◽  
Fish And Shellfish ◽  
Long Chain

BACKGROUND: In Western populations, long-chain n-3 polyunsaturated fatty acid (LCn3FAs) intake was shown to be inversely associated with the risk of cardiovascular diseases, particularly that of cardiac disease. Dietary intake of LCn3FAs among Japanese is generally higher than those of Western populations due to their higher intake of fish and shellfish. However, little is known regarding whether an inverse association exists in a population with higher LCn3FAs intake. Furthermore, evidence for association with stroke risk has been limited. OBJECTIVES: To investigate the association between LCn3FAs intake and the risk of cardiovascular diseases and stroke in a Japanese general population. METHODS: We followed-up a total of 9,190 community-dwelling individuals (56.1% women, mean age of 50.0 years) randomly selected from 300 areas across Japan and free from cardiovascular diseases at baseline. Dietary LCn3FAs intake was estimated using household weighed food records. Cox models were used to calculate multivariable adjusted hazard ratios (HRs) and 95% confidence interval (95%CI) according to sex specific quartiles of LCn3FAs intake. HRs were adjusted for age, sex, cardiovascular risk factors, dietary sodium and other nutritional factors. RESULTS: During 24 years of follow-up, 879 cardiovascular deaths were observed. The median daily intake of LCn3FAs was 0.37%kcal. Median value of the lowest quartile of LCn3FAs intake (0.18%kcal) in the present study was twice as high as the average intake in U.S. population. Adjusted HR for cardiovascular disease mortality was lower in the highest quartile of LCn3FAs intake (HR 0.80; 95%CI, 0.66-0.96) compared with the lowest quartile, and the trend was significant ( P =0.038). The similar but statistically non- significant trends were observed for cardiac death and stroke death. CONCLUSIONS: In a representative sample of Japanese with high LCn3FAs intake, the risk of total cardiovascular disease mortality was inversely and independently associated with LCn3FAs intake, and the risk of stroke also showed similar tendency.

scholarly journals Congener specific distribution of polychlorinated dibenzo-p-dioxins and dibenzo-p-furans in ambient air particulates (less than PM10) in Delhi, India

2012 ◽  
Vol 2 (1) ◽  
pp. 7 ◽  
Author(s):  
Bhupander Kumar ◽  
Satish Kumar Singh ◽  
Ram Bharoshey Lal ◽  
Sanjay Kumar ◽  
Chandra Shekhar Sharma
Keyword(s):  
Pollution Control ◽  
National Level ◽  
Daily Intake ◽  
Ambient Air ◽  
Stockholm Convention ◽  
World Health ◽  
Specific Distribution ◽  
Central Pollution Control Board ◽  
Risk Of Exposure ◽  
Health Organization

Polychlorinated dibenzo-<em>p</em>-dioxins (PCDDs) and polychlorinated dibenzo-<em>p</em>-furans (PCDFs) are unintentionally formed during inefficient combustions and as a by-product. Due to their resistance to degradation and their toxic effect on health, PCDD/Fs are listed by the Stockholm Convention as persistent organic pollutants (POPs). Once released into the atmosphere, most of them are adsorbed to air particles and transported away from sources in atmosphere. India signed the Stockholm Convention India agreeing thereby to reduce and eliminate the use of POPs. The German agency for Technical Cooperation helped develop facilities for monitoring POPs at a national level in Delhi. This paper presents the data generated during a training assignment for Central Pollution Control Board officials at the German laboratory. Air borne particulate matter (&lt;PM<sub>10</sub>) was collected from 6 different locations in Delhi, India and analyzed in a German laboratory for 17 congeners of PCDD/Fs. The concentrations of &Sigma;PCDD/Fs ranged between 1720-9010 fg m<sup>-3</sup> (mean 5559 fg m<sup>-3</sup>) and their toxic equivalency values ranged from 67 to 460 fg I-toxic equivalent quantities (TEQ) m<sup>-3</sup>, with an average of 239 fg I-TEQ m<sup>-3</sup> which was lower than the ambient air standards. The dominant congeners were octachlorinated dibenzo-p-dioxin (OCDD), octachlorinated dibenzo-p-furans (OCDF), 1,2,3,4,6,7,8-heptachlorinated dibenzo- p-furans, and 1,2,3,4,6,7,8-heptachlorinated dibenzo-p-dioxin. The contributions of individual homologs for &Sigma;PCDDs/Fs I-TEQ was in the order of OCDD (31%)&gt;HCDF (21%)&gt;hexachlorodibenzofurans (13%)=OCDF (13%)&gt; HCDF (12%) and other individual congeners contribute less than 5%. High chlorinated congeners contributed with more than 80% for &Sigma;PCDD/Fs I-TEQ. Rough estimates of tolerable daily intake (TDI) shows low health risk of exposure to &Sigma;PCDD/Fs with inhalation of 0.098 pg I-TEQ kg<sup>1</sup>day<sup>1</sup> for adult and 0.152 pg TEQ kg<sup>-1</sup>day<sup>-1</sup> for children, which is much lower than World Health Organization recommended TDI for dioxins.

scholarly journals Rodent Models for Metabolic Syndrome Research

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Sunil K. Panchal ◽  
Lindsay Brown
Keyword(s):  
Metabolic Syndrome ◽  
Therapeutic Interventions ◽  
Rodent Models ◽  
High Fat ◽  
Disease Symptoms ◽  
The Metabolic Syndrome ◽  
Progression Of Disease ◽  
Liver And Kidney ◽  
Heart Blood ◽  
The Many

Rodents are widely used to mimic human diseases to improve understanding of the causes and progression of disease symptoms and to test potential therapeutic interventions. Chronic diseases such as obesity, diabetes and hypertension, together known as the metabolic syndrome, are causing increasing morbidity and mortality. To control these diseases, research in rodent models that closely mimic the changes in humans is essential. This review will examine the adequacy of the many rodent models of metabolic syndrome to mimic the causes and progression of the disease in humans. The primary criterion will be whether a rodent model initiates all of the signs, especially obesity, diabetes, hypertension and dysfunction of the heart, blood vessels, liver and kidney, primarily by diet since these are the diet-induced signs in humans with metabolic syndrome. We conclude that the model that comes closest to fulfilling this criterion is the high carbohydrate, high fat-fed male rodent.

scholarly journals Selenium in Human Health and Gut Microflora: Bioavailability of Selenocompounds and Relationship With Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Rannapaula Lawrynhuk Urbano Ferreira ◽  
Karine Cavalcanti Maurício Sena-Evangelista ◽  
Eduardo Pereira de Azevedo ◽  
Francisco Irochima Pinheiro ◽  
Ricardo Ney Cobucci ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Current Knowledge ◽  
Daily Intake ◽  
Experimental Studies ◽  
Selenium Deficiency ◽  
Intestinal Bacteria ◽  
Microbial Colonization ◽  
Gut Microflora ◽  
Symbiotic Relationship ◽  
Selenium Status

This review covers current knowledge of selenium in the dietary intake, its bioavailability, metabolism, functions, biomarkers, supplementation and toxicity, as well as its relationship with diseases and gut microbiota specifically on the symbiotic relationship between gut microflora and selenium status. Selenium is essential for the maintenance of the immune system, conversion of thyroid hormones, protection against the harmful action of heavy metals and xenobiotics as well as for the reduction of the risk of chronic diseases. Selenium is able to balance the microbial flora avoiding health damage associated with dysbiosis. Experimental studies have shown that inorganic and organic selenocompounds are metabolized to selenomethionine and incorporated by bacteria from the gut microflora, therefore highlighting their role in improving the bioavailability of selenocompounds. Dietary selenium can affect the gut microbial colonization, which in turn influences the host's selenium status and expression of selenoproteoma. Selenium deficiency may result in a phenotype of gut microbiota that is more susceptible to cancer, thyroid dysfunctions, inflammatory bowel disease, and cardiovascular disorders. Although the host and gut microbiota benefit each other from their symbiotic relationship, they may become competitors if the supply of micronutrients is limited. Intestinal bacteria can remove selenium from the host resulting in two to three times lower levels of host's selenoproteins under selenium-limiting conditions. There are still gaps in whether these consequences are unfavorable to humans and animals or whether the daily intake of selenium is also adapted to meet the needs of the bacteria.

UTILIZATION BY THE RAT OF LARGE LIVER RESERVES OR OF A SMALL DAILY INTAKE OF VITAMIN A

1962 ◽  
Vol 40 (10) ◽  
pp. 1407-1413
Author(s):  
T. K. Murray
Keyword(s):  
Growth Rate ◽  
Vitamin A ◽  
Normal Development ◽  
Daily Intake ◽  
Entire Period ◽  
Female Rats ◽  
Liver And Kidney ◽  
Weaning Age ◽  
Normal Males ◽  
Sufficient Vitamin

Weanling female rats were given a massive dose of vitamin A and thereafter fed a vitamin A free diet while similar rats were provided with the same diet plus a small daily intake of vitamin A for the entire period. Some of the rats from each group were bred to normal males. There were no differences in the growth rate, the number of young produced and weaned, nor in the weight of the young. Somewhat more vitamin A was transferred to the liver and kidney of the young by mothers with large liver stores but these differences had disappeared by weaning age. It was concluded that sufficient vitamin A could be given a rat at weaning to allow normal development and the production of at least one normal litter.

Adverse effects of lactational exposure to chlorpyrifos in suckling rats

2009 ◽  
Vol 29 (2) ◽  
pp. 77-92 ◽  
Author(s):  
SA Mansour ◽  
AH Mossa
Keyword(s):  
Body Weight ◽  
Adverse Effects ◽  
Body Weight Gain ◽  
Lethal Dose ◽  
Daily Intake ◽  
Oral Route ◽  
The Body ◽  
Lactational Exposure ◽  
Histopathological Alterations ◽  
Liver And Kidney

The present study was undertaken to evaluate the oxidative damage, biochemical and histopathological alterations in sucking rats whose mothers were exposed to the insecticide chlorpyrifos (CPF). Dams were administered CPF, via oral route. Doses equalled 0.01 mg kg—1 body weight (b.wt.; acceptable daily intake, ADI), 1.00 mg kg—1 b.wt. (no observed adverse effects level, NOAEL) and 1.35 mg kg—1 b.wt. (1/100 lethal dose [LD50]) from postnatal day 1 until day 20 after delivery. At two high doses of CPF, the body weight gain and relative liver and kidney weight of suckling pups were significantly decreased. Exposure of the mothers to CPF caused increase in lipid peroxidation (LPO) and decrease in superoxide dismutase (SOD) and glutathione-s-transferase (GST) in lactating pups. CPF altered the level of the marker parameters related to the liver and kidneys. Consistent histological changes were found in the liver and kidneys of the subjected pups, especially at the higher doses. The results suggested that the transfer of CPF intoxication through the mother’s milk has resulted in oxidative stress and biochemical and histopathological alterations in the suckling pups. The data of this study may be considered as a contribution to the problem of lactational transfer of the relatively less persistent OP pesticides, such as CPF.

scholarly journals Oral bioavailability of ATP after prolonged administration

2010 ◽  
Vol 105 (3) ◽  
pp. 357-366 ◽  
Author(s):  
Erik J. C. M. Coolen ◽  
Ilja C. W. Arts ◽  
Otto Bekers ◽  
Chris Vervaet ◽  
Aalt Bast ◽  
...  
Keyword(s):  
Uric Acid ◽  
Oral Administration ◽  
Healthy Subjects ◽  
Animal Studies ◽  
Purinergic Receptors ◽  
Daily Intake ◽  
Prolonged Administration ◽  
Liver And Kidney ◽  
Enteric Coated ◽  
To Receive

Purinergic receptors are important for the regulation of inflammation, muscle contraction, neurotransmission and nociception. Extracellular ATP and its metabolites are the main ligands for these receptors. Occasional reports on beneficial results of ATP administration in human and animal studies have suggested the bioavailability of oral ATP supplements. We investigated whether prolonged daily intake of oral ATP is indeed bioavailable. Thirty-two healthy subjects were randomised to receive 0, 250, 1250 or 5000 mg ATP per d for 28 d by means of enteric-coated pellets. In addition, on days 0 and 28, all thirty-two subjects received 5000 mg ATP to determine whether prolonged administration would induce adaptations in the bioavailability of ATP. ATP supplementation for 4 weeks did not lead to changes in blood or plasma ATP concentrations. Of all ATP metabolites, only plasma uric acid levels increased significantly after the administration of 5000 mg of ATP. Prolonged administration of ATP was safe as evidenced from liver and kidney parameters. We conclude that oral administration of ATP only resulted in increased uric acid concentrations. On the basis of these findings, we seriously question the claimed efficacy of oral ATP at dosages even lower than that used in the present study.

Dietary influences on excretory pathways and tissue residues of zearalenone and zearalenols in the rat

1982 ◽  
Vol 60 (12) ◽  
pp. 1444-1449 ◽  
Author(s):  
T. K. Smith
Keyword(s):  
Anion Exchange ◽  
Exchange Resin ◽  
Anion Exchange Resin ◽  
High Protein ◽  
Fecal Excretion ◽  
Free Form ◽  
Weanling Rats ◽  
Liver And Kidney ◽  
High Protein Diets ◽  
Protein Diets

Experiments were conducted with male weanling rats to determine the effect of high dietary protein (40% casein), alfalfa (25%), protein + alfalfa (25% casein + 25%) alfalfa), or anion-exchange resin (5%) on the relative proportions of free and conjugated zearalenone and zearalenols excreted in urine and feces following a single oral dose of zearalenone. About 90% of the dose was excreted in feces after 48 h while the remaining 10% was excreted in urine. Zearalenone and metabolites were excreted mainly in free form with conjugates being found only in urine. Rats fed high-protein diets excreted more free zearalenone and α-zearalenol in urine than did controls (16.3% casein). The feeding of protein + alfalfa also resulted in increased urinary losses of free zearalenone. A reduction in urinary losses of conjugated zearalenone and α-zearalenol was seen when 5% anion-exchange resin was fed. Fecal excretion of zearalenone and α- and β-zearalenol increased when alfalfa + protein was fed. Residual zearalenone and zearalenols were measured in liver and kidney 18 h after dosing. All treatments except high protein reduced residues of zearalenone and α-zearalenol in liver when compared with controls. Renal residues of zearalenone were lowered only by supplements of protein + alfalfa or anion-exchange resin. Each of the treatments fed has been shown to reduce zearalenone toxicosis in rats, but it was concluded that each does so by a different mechanism.

scholarly journals Obesity-Linked Cancers: Current Knowledge, Challenges and Limitations in Mechanistic Studies and Rodent Models

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 523 ◽  
Author(s):  
Yang Xu ◽  
Suresh Mishra
Keyword(s):  
Current Knowledge ◽  
Psychosocial Health ◽  
Rodent Models ◽  
Mechanistic Studies ◽  
Multiple Cancer ◽  
The People ◽  
Incidence And Mortality ◽  
Prevalence Of Obesity ◽  
Clinical Models ◽  
Cancer Types

The worldwide prevalence of obesity has doubled during the last 50 years, and according to the World Obesity Federation, one third of the people on Earth will be obese by the year 2025. Obesity is described as a chronic, relapsing and multifactorial disease that causes metabolic, biomechanical, and psychosocial health consequences. Growing evidence suggests that obesity is a risk factor for multiple cancer types and rivals smoking as the leading preventable cause for cancer incidence and mortality. The epidemic of obesity will likely generate a new wave of obesity-related cancers with high aggressiveness and shortened latency. Observational studies have shown that from cancer risk to disease prognosis, an individual with obesity is consistently ranked worse compared to their lean counterpart. Mechanistic studies identified similar sets of abnormalities under obesity that may lead to cancer development, including ectopic fat storage, altered adipokine profiles, hormone fluctuations and meta-inflammation, but could not explain how these common mechanisms produce over 13 different cancer types. A major hurdle in the mechanistic underpinning of obesity-related cancer is the lack of suitable pre-clinical models that spontaneously develop obesity-linked cancers like humans. Current approaches and animal models fall short when discerning the confounders that often coexist in obesity. In this mini-review, we will briefly survey advances in the different obesity-linked cancers and discuss the challenges and limitations in the rodent models employed to study their relationship. We will also provide our perspectives on the future of obesity-linked cancer research.

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