scholarly journals The effect of sublethal short-duration exposure of paraoxon on pregnancy and fetuses in mice

2015 ◽  
Vol 67 (3) ◽  
pp. 861-867
Author(s):  
Syed Nurulain ◽  
Mohamed Shafiullah ◽  
Charu Sharma ◽  
Mahmoud Ali ◽  
Shreesh Ojha

A convincing number of epidemiological studies have reported on the exposure to and consequences of organophosphorus compounds (OPCs) in pregnant women. However, there is still a knowledge gap and paucity of systematic literature from animal studies. This study was undertaken with the hypothesis that short-duration sublethal exposure to OPCs can produce maternal and fetal lethal effects as chronic exposure. This study examineses the teratogenicity and embryotoxicity of paraoxon (POX) in mice at a dose that is non-lethal to non-pregnant mothers. Pregnant mice were injected intraperitoneally (i.p.) with paraoxon (50 nmol/mouse) on the 4th and 5th days of gestation, and the effect of the treatment was assessed on day 18 of gestation. This dose was fatal to pregnant mice in 21% of instances as compared to non-pregnant animals in which 0% mortality was detected, even after daily injection of a similar dose for five days. Significant inhibition of red blood cell acetylcholinesterase (RBC-AChE) was observed in pregnant mice as compared to non-pregnant ones; however, no apparent neuronal effect was detected. Of note were fetal weight decrement, pregnancy termination, intrauterine growth retardation and maternal death. We concluded that exposure to even a non-toxic dose might be critical for pregnant mothers, the pregnancy as well as fetuses. In addition, even exposure of short duration can be detrimental and capable of producing profound and fatal effects.

2003 ◽  
Vol 90 (2) ◽  
pp. 457-465 ◽  
Author(s):  
Ho Yee Chan ◽  
Lai K. Leung

Epidemiological studies indicate that Asian women have a lower breast cancer incidence compared with their counterparts in the West, and the difference has been related to soya consumption. Animal studies have suggested that soya may prevent dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in the breast. In the present study a cell culture model was developed to address the effect of soya isoflavones on the DMBA-induced DNA damage. DMBA is metabolized into a DNA-attacking moiety by two phase I cytochrome P450 (CYP) enzymes CYP1A1 and CYP1B1. DNA mutation caused by this genotoxic agent is a crucial step in cancer initiation. Substances that interfere with the CYP1 enzyme activities can affect the initiation. In the present study, genistein was found to be an effective inhibitor of recombinant human CYP1A1 and CYP1B1 with Ki of 15·35 and 0·68 μmol/l. The other soya isoflavone daidzein, on the other hand, did not demonstrate any significant inhibition of the enzyme activities. At the transcriptional level, DMBA induced the CYP1 enzyme expressions by stimulating the xenobiotic response element (XRE)-dependent transactivation pathway. When genistein (25 μmol/l) was co-administered with DMBA, the XRE-Luc activity the CYP1 mRNA abundances were significantly suppressed. The present study illustrated that the soya isoflavone genistein, but not daidzein, protected against DMBA genotoxicity.


1991 ◽  
Vol 77 (3) ◽  
pp. 159-164
Author(s):  
K. A. Peterson ◽  
S. J. Portouw

AbstractThe war in the Gulf and the resultant massive oil spill has prompted an assessment of the health hazards to naval divers operating in oil-fouled environments. A review of current literature and discussions with experts in the field was undertaken to assess these hazards. With the assistance of Kuwait Petroleum, an assay of the content of average Kuwait crude was obtained. The risks of contact with crude oil and its vapours via the skin, inhalation and ingestion have been assessed. Contact dermatitis is the most likely sequel. A chemical pneumonitis from oil inhalation is possible but extremely unlikely. A health risk from ingestion of crude oil is equally unlikely since no toxic effect is thought to occur below a consumption of 5 ml/kg (350 ml for an average diver). Trace metals were found to be at a level of less than 1/10 of the minimal toxic dose for all but vanadium. No increased risk of skin cancer can be found in animal studies of crude oil. Epidemiological studies have recorded no increased risk of bladder or thyroid cancer in petroleum workers, but an increase in lung, nasal cavity, sinus and skin cancer has been shown following chronic exposure to low levels of petroleum vapour. No medical indication was found for modification of existing operational procedures, although, since the toxicity of some components of crude oil is unknown, the use of improved equipment to avoid contact should be studied.


Biomolecules ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 99 ◽  
Author(s):  
Danja J. Den Hartogh ◽  
Evangelia Tsiani

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties. The current review summarizes the existing in vitro and in vivo animal studies examining the anti-diabetic effects of naringenin.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Marlene Cervantes González

Abstract Persistent Organic Pollutants (POPs) are exogenous, artificially made chemicals that can disrupt the biological system of individuals and animals. POPs encompass a variety of chemicals including, dioxins, organochlorines (OCs), polychlorinated biphenyl (PCBs), and perfluoroalkyl substances (PFASs) that contain a long half-life and highly resistant to biodegradation. These environmental pollutants accumulate over time in adipose tissues of living organisms and alter various insulin function-related genes. Childhood Metabolic Syndrome (MetS) consists of multiple cardiovascular risk factors, insulin function being one of them. Over the years, the incidence of the syndrome has increased dramatically. It is imperative to explore the role of persistent organic pollutants in the development of Childhood Metabolic Syndrome. Some epidemiological studies have reported an association between prenatal exposure to POPs and offspring MetS development throughout childhood. These findings have been replicated in animal studies in which these pollutants exercise negative health outcomes such as obesity and increased waist circumference. This review discusses the role of prenatal exposure to POPs among offspring who develop MetS in childhood, the latest research on the MetS concept, epidemiological and experimental findings on MetS, and the POPs modes of action. This literature review identified consistent research results on this topic. Even though the studies in this review had many strengths, one major weakness was the usage of different combinations of MetS criteria to measure the outcomes. These findings elucidate the urgent need to solidify the pediatric MetS definition. An accurate definition will permit scientists to measure the MetS as a health outcome properly and allow clinicians to diagnose pediatric MetS and provide individualized treatment appropriately.


2010 ◽  
Vol 23 (1) ◽  
pp. 4-22 ◽  
Author(s):  
Paul Guilloteau ◽  
Romuald Zabielski ◽  
Harald M. Hammon ◽  
Cornelia C. Metges

The consequences of early-life nutritional programming in man and other mammalian species have been studied chiefly at the metabolic level. Very few studies, if any, have been performed in the gastrointestinal tract (GIT) as the target organ, but extensive GIT studies are needed since the GIT plays a key role in nutrient supply and has an impact on functions of the entire organism. The possible deleterious effects of nutritional programming at the metabolic level were discovered following epidemiological studies in human subjects, and confirmed in animal models. Investigating the impact of programming on GIT structure and function would need appropriate animal models due to ethical restrictions in the use of human subjects. The aim of the present review is to discuss the use of pigs as an animal model as a compromise between ethically acceptable animal studies and the requirement of data which can be interpolated to the human situation. In nutritional programming studies, rodents are the most frequently used model for man, but GIT development and digestive function in rodents are considerably different from those in man. In that aspect, the pig GIT is much closer to the human than that of rodents. The swine species is closely comparable with man in many nutritional and digestive aspects, and thus provides ample opportunity to be used in investigations on the consequences of nutritional programming for the GIT. In particular, the ‘sow–piglets’ dyad could be a useful tool to simulate the ‘human mother–infant’ dyad in studies which examine short-, middle- and long-term effects and is suggested as the reference model.


2020 ◽  
Author(s):  
Sara Ruth Westbrook ◽  
Lauren Carrica ◽  
Asia Banks ◽  
Joshua Michael Gulley

Adolescent use of amphetamine and its closely related, methylated version methamphetamine, is alarmingly high in those who use drugs for nonmedical purposes. This raises serious concerns about the potential for this drug use to have a long-lasting, detrimental impact on the normal development of the brain and behavior that is ongoing during adolescence. In this review, we explore recent findings from both human and laboratory animal studies that investigate the consequences of amphetamine and methamphetamine exposure during this stage of life. We highlight studies that assess sex differences in adolescence, as well as those that are designed specifically to address the potential unique effects of adolescent exposure by including groups at other life stages (typically young adulthood). We consider epidemiological studies on age and sex as vulnerability factors for developing problems with the use of amphetamines, as well as human and animal laboratory studies that tap into age differences in use, its short-term effects on behavior, and the long-lasting consequences of this exposure on cognition. We also focus on studies of drug effects in the prefrontal cortex, which is known to be critically important for cognition and is among the later maturing brain regions. Finally, we discuss important issues that should be addressed in future studies so that the field can further our understanding of the mechanisms underlying adolescent use of amphetamines and its outcomes on the developing brain and behavior.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Johri ◽  
M F Hetu ◽  
D K Heyland ◽  
J E Herr ◽  
P Norman ◽  
...  

Abstract Background/Introduction L-carnitine (L-C) has been investigated as a potential therapy for cardiovascular (CV) disease, but its direct effects on human atherosclerosis are unknown. Epidemiological studies suggest a possible reduction of CV risk factors following treatment, whereas animal studies have shown that L-C may increase pro-atherogenic metabolites. Purpose The purpose of this study was to determine whether L-C therapy led to atherosclerosis progression or regression by direct quantification of carotid atherosclerotic lesions in patients with metabolic syndrome (MetS). Methods This study was a Phase 2, prospective, parallel, double blinded, randomized, placebo-controlled, two-center trial. MetS was defined according to the International Diabetes Federation harmonized definition, where presence of any 3 of the 5 following risk factors constituted a diagnosis: elevated waist circumference; elevated triglycerides; reduced HDL or treated; elevated blood pressure or treated; elevated glucose or HbA1c or treated. Participants with a baseline carotid total plaque volume (TPV) ≥50 mm3 were randomized to placebo or 2 g L-C daily for 6 months. Plaque progression was quantified by 3D carotid ultrasound for change in TPV and reduction in vessel lumen area (% area stenosis, Fig. 1). Absolute differences were assessed on the raw scale, while percent change on the log scale. Analysis of covariance (ANCOVA) was used to assess within- and between-arm differences. Results Of the 177 participants randomized, 157 completed the study (L-C n=76, placebo n=81). No statistically significant difference between arms was found in the primary outcome (TPV). However, there was progression of plaque stenosis in the treatment arm: the L-C group had an increase in stenosis of 9.8% (p=0.01) higher than the placebo arm, and a 2.7% (p=0.03) greater absolute change. Total cholesterol and LDL levels (0.10 mmol/L and 0.05 mmol/L, respectively) were higher in the intervention arm compared to the placebo arm (−0.06 mmol/L and −0.07 mmol/L). Figure 1 Conclusions We observed progression of atherosclerosis with L-C therapy compared to placebo in patients with MetS. The clear lack of benefit of L-C therapy in this population raises serious concerns for its further use as a potential therapy. Given its association with pro-atherogenic metabolites our study offers further understanding of the atherosclerotic process. Acknowledgement/Funding Heart and Stroke Foundation of Canada


1999 ◽  
Vol 22 (2) ◽  
pp. 218-218 ◽  
Author(s):  
Paul F. Brain

The view that female mammals are more docile appears to arise in part from imposing human values on animal studies. Many reports of sexual dimorphism in physical aggression favouring the male in laboratory rodents appear to select circumstances where that expectation is supported. Other situations that favour the expression of conflict in females have been (until recently) relatively little studied. Although female rodents generally do not show the “ritualised” forms of conflict that characterise male sexual competition, they can use notably damaging strategies (especially if they are of short duration). Such considerations might weigh in the selection of strategies by our own species.


Toxics ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 21 ◽  
Author(s):  
Yu Wang ◽  
Hongkai Zhu ◽  
Kurunthachalam Kannan

Phthalates (diesters of phthalic acid) are widely used as plasticizers and additives in many consumer products. Laboratory animal studies have reported the endocrine-disrupting and reproductive effects of phthalates, and human exposure to this class of chemicals is a concern. Several phthalates have been recognized as substances of high concern. Human exposure to phthalates occurs mainly via dietary sources, dermal absorption, and air inhalation. Phthalates are excreted as conjugated monoesters in urine, and some phthalates, such as di-2-ethylhexyl phthalate (DEHP), undergo secondary metabolism, including oxidative transformation, prior to urinary excretion. The occurrence of phthalates and their metabolites in urine, serum, breast milk, and semen has been widely reported. Urine has been the preferred matrix in human biomonitoring studies, and concentrations on the order of several tens to hundreds of nanograms per milliliter have been reported for several phthalate metabolites. Metabolites of diethyl phthalate (DEP), dibutyl- (DBP) and diisobutyl- (DiBP) phthalates, and DEHP were the most abundant compounds measured in urine. Temporal trends in phthalate exposures varied among countries. In the United States (US), DEHP exposure has declined since 2005, whereas DiNP exposure has increased. In China, DEHP exposure has increased since 2000. For many phthalates, exposures in children are higher than those in adults. Human epidemiological studies have shown a significant association between phthalate exposures and adverse reproductive outcomes in women and men, type II diabetes and insulin resistance, overweight/obesity, allergy, and asthma. This review compiles biomonitoring studies of phthalates and exposure doses to assess health risks from phthalate exposures in populations across the globe.


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