scholarly journals Early-Life Exposure to Low-Dose Cadmium Accelerates Diethylnitrosamine and Diet-Induced Liver Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Hongbo Men ◽  
Jamie L. Young ◽  
Wenqian Zhou ◽  
Haina Zhang ◽  
Xiang Wang ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Early Life ◽  
Low Dose ◽  
Liver Tumors ◽  
Cadmium Exposure ◽  
Male Mice ◽  
Nonalcoholic Fatty Liver ◽  
Early Life Exposure ◽  
The Impact

Maternal exposure to cadmium causes obesity and metabolic changes in the offspring, including nonalcoholic fatty liver disease-like pathology. However, whether maternal cadmium exposure accelerates liver cancer in the offspring is unknown. This study investigated the impact of early-life exposure to cadmium on the incidence and potential mechanisms of hepatocellular carcinoma (HCC) in offspring subjected to postweaning HCC induction. HCC in C57BL/6J mice was induced by diethylnitrosamine (DEN) injection at weaning, followed by a long-term high-fat choline-deficient (HFCD) diet. Before weaning, liver cadmium levels were significantly higher in mice with early-life cadmium exposure than in those without cadmium exposure. However, by 26 and 29 weeks of age, hepatic cadmium fell to control levels, while a significant decrease was observed in copper and iron in the liver. Both male and female cadmium-exposed mice showed increased body weight compared to non-cadmium-treated mice. For females, early-life cadmium exposure also worsened insulin intolerance but did not significantly promote DEN/HFCD diet-induced liver tumors. In contrast, in male mice, early-life cadmium exposure enhanced liver cancer induction by DEN/HFCD with high incidence and larger liver tumors. The liver peritumor tissue of early-life cadmium-exposed mice exhibited greater inflammation and disruption of fatty acid metabolism, accompanied by higher malondialdehyde and lower esterified triglyceride levels compared to mice without cadmium exposure. These findings suggest that early-life exposure to low-dose cadmium accelerates liver cancer development induced by a DEN/HFCD in male mice, probably due to chronic lipotoxicity and inflammation caused by increased uptake but decreased consumption of fatty acids.

scholarly journals Sex dependent effects of post-natal penicillin on brain, behavior and immune regulation are prevented by concurrent probiotic treatment

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marya Kayyal ◽  
Tanvi Javkar ◽  
M. Firoz Mian ◽  
Dana Binyamin ◽  
Omry Koren ◽  
...  
Keyword(s):  
Early Life ◽  
Low Dose ◽  
Metabolic Diseases ◽  
Immune Cell ◽  
Male Mice ◽  
Long Term Effects ◽  
Probiotic Treatment ◽  
Relevant Dose ◽  
Brain Behavior

Abstract There is increasing awareness of the need to consider potential long-term effects of antibiotics on the health of children. In addition to being associated with immune and metabolic diseases, there is evidence that early-life antibiotic exposure can affect neurodevelopment. Here we investigated the effect of low dose of penicillin V on mice when administered for 1 week immediately prior to weaning. We demonstrated that exposure to the antibiotic during the pre-weaning period led to long-term changes in social behaviour, but not anxiety-like traits, in male mice only. The change in behaviour of males was associated with decreased hippocampal expression of AVPR1A and AVPR1B while expression of both receptors was increased in females. Spleens of male mice also showed an increase in the proportion of activated dendritic cells and a corresponding decrease in regulatory T cells with penicillin exposure. All changes in brain, behaviour and immune cell populations, associated with penicillin exposure, were absent in mice that received L. rhamnosus JB-1 supplementation concurrent with the antibiotic. Our study indicates that post-natal exposure to a clinically relevant dose of antibiotic has long-term, sex dependent effects on the CNS and may have implications for the development of neuropsychiatric disorders. Importantly, we also provide further evidence that probiotic based strategies may be of use in counteracting detrimental effects of early-life antibiotics on neurodevelopment.

IMPACT OF EARLY LIFE STRESS ON ANTI-DEPRESSANT SENSITIVITY

2021 ◽  
pp. 123-132
Author(s):  
V.A. Vokina
Keyword(s):  
Open Field ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Anxiety Level ◽  
Male Rats ◽  
Porsolt Test ◽  
The Impact ◽  
Sexually Mature

Long-term consequences of impaired perinatal development are very significant. They appear during the neonatal period and in the first years of life, and persist during ontogenesis. There is little data on the impact of any prenatal factors on the sensitivity of a sexually mature organism to medications. The aim of the study is to assess the impact of early life stress on the development of individual antidepressant sensitivity. Materials and Methods. The authors conducted the experiments on sexually mature outbred male rats. To simulate the early life stress, a standard protocol was used. From the 2nd to 15th days of the postnatal period the pup rats were separated from their mother for 3 hours and kept in an incubator. The open-field test, Porsolt test and Sucrose consumption test were used to determine rat’s anxiety level as well as motor, orientation and exploratory activity at puberty. Then, for 14 days, the rats were intragastrically administered with a fluoxetine solution (10 mg/kg/daily), followed by their full examination. Statistical analysis of results was performed using the Mann-Whitney U-test to compare unrelated groups and Wilcoxon's test to compare related groups. Results. Fluoxetine did not have a pronounced antidepressant effect in animals that survived the early life stress. Such animals demonstrated passive floating during the Porsolt test, without any changes in immobility time. When testing in an open field, a sharp increase in the number of freezing behavior was observed, which was an indicator of an increased anxiety level in animals. Conclusion. The results obtained indicate that the long-term effects of neonatal stress may be associated with a change in antidepressant sensitivity or an increase in development of unwanted adverse reactions. Keywords: early life stress, depression, antidepressants, fluoxetine, rats. Отдаленные последствия нарушения перинатального развития весьма значительны и не только проявляются в период новорожденности и в первые годы жизни, но и сохраняются в период онтогенеза. Данные о влиянии каких-либо пренатальных факторов на чувствительность половозрелого организма к действию лекарственных веществ в доступной литературе представлены незначительно. Цель исследования – оценить роль стресса раннего периода жизни в формировании индивидуальной чувствительности к действию антидепрессантов. Материалы и методы. Эксперименты проведены на половозрелых беспородных крысах-самцах. Для моделирования стресса раннего периода жизни использовали стандартный протокол, подразумевающий отделение детенышей от матери со 2-го по 15-й дни постнатального периода на 3 ч в условиях инкубатора. В половозрелом возрасте проводили оценку уровня тревожности, двигательной и ориентировочно-исследовательской активности крыс в условиях теста открытого поля, теста Порсолта и теста «Потребление раствора сахарозы». Затем в течение 14 дней крысам внутрижелудочно вводили раствор флуоксетина (10 мг/кг/сут), после чего обследование повторяли в том же объеме. Статистический анализ результатов исследования проводили с использованием U-критерия Манна–Уитни для сравнения несвязанных групп и критерия Вилкоксона для сравнения связанных групп. Результаты. У животных, переживших стресс раннего периода жизни, флуоксетин не оказывал выраженного антидепрессантного действия. У данных животных в тесте Порсолта преобладало пассивное плавание, без изменения длительности иммобильности. При тестировании в открытом поле наблюдалось резкое повышение числа актов фризинга, что является показателем повышенного уровня тревожности у животных. Выводы. Полученные результаты свидетельствуют о том, что отдаленные последствия неонатального стресса могут быть связанны с изменением чувствительности к действию антидепрессантов или повышением риска развития нежелательных побочных реакций. Ключевые слова: стресс раннего периода жизни, депрессия, антидепрессанты, флуоксетин, крысы.

scholarly journals Stress and Growth in children and adolescents

2021 ◽  
Author(s):  
Maria Mousikou ◽  
Andreas Kyriakou ◽  
Nicos Skordis
Keyword(s):  
Growth Hormone ◽  
Stress Response ◽  
Chronic Stress ◽  
Early Life ◽  
Stress System ◽  
Childhood And Adolescence ◽  
Conservation Of Energy ◽  
Targeted Interventions ◽  
The Impact

The infantile, childhood, and adolescent periods of growth and development represent times of increased vulnerability to stressors. The rate of growth in each period depends on the interplay of genetic, environmental, dietary, socioeconomic, developmental, behavioral, nutritional, metabolic, biochemical, and hormonal factors. A stressor may have an impact on growth directly through modulation of the growth hormone axis or indirectly through modulation of other factors. The adaptive response to stressors culminates in behavioral, physiological, and biochemical responses, which together support survival and conservation of energy. The process begins within seconds and involves activation of sympathetic nervous system and Hypothalamic-Pituitary-Adrenal axis. The time-limited stress response is at once anti-growth, anti-reproductive and catabolic with no lasting adverse consequences. However, chronic activation of the stress system and hypercortisolism have consequential negative impacts on growth, thyroid function, reproduction-puberty, and metabolism. They suppress Growth Hormone-Insulin like growth factor 1, Hypothalamic-Pituitary-Gonadal and Thyroid axes and can be responsible for an increase in visceral adiposity, a decrease in lean mass, suppression of osteoblastic activity with risk of osteoporosis, and induction of insulin resistance. Early life adversities, emotional or physical, have been associated with long-term negative physical and mental health outcomes. There are many models of chronic stress that corroborate that early life adversities affect optimal growth and have consequences throughout the lifespan. Targeted interventions to reduce stress during infancy, childhood and adolescence can have far reaching benefits to long-term health as well as attaining adequate growth. In this review we describe the neuroendocrinology of the stress response, the factors influencing growth, and the impact of chronic stress on growth during critical periods of infancy, childhood, and puberty with reference to each of growth, thyroid, and gonadal axis.

Long-Term Exposure to Low-Dose Lead Induced Deterioration in Bone Microstructure of Male Mice

2019 ◽  
Vol 195 (2) ◽  
pp. 491-498 ◽  
Author(s):  
Zhijie Sheng ◽  
Shuai Wang ◽  
Xiang Zhang ◽  
Xiaoyin Li ◽  
Bingyan Li ◽  
...  
Keyword(s):  
Low Dose ◽  
Bone Microstructure ◽  
Male Mice

scholarly journals Low-dose colchicine prevents sympathetic denervation after myocardial ischemia-reperfusion: a new potential protective mechanism

2021 ◽  
Vol 7 (2) ◽  
pp. FSO656
Author(s):  
Fabien Huet ◽  
Jérémy Fauconnier ◽  
Marion Legall ◽  
Pierre Sicard ◽  
Catherine Lozza ◽  
...  
Keyword(s):  
Left Coronary Artery ◽  
Low Dose ◽  
Ischemia Reperfusion ◽  
Colchicine Treatment ◽  
Sympathetic Denervation ◽  
Protective Mechanism ◽  
Male Mice ◽  
Variability Index ◽  
Myocardial Ischemia Reperfusion ◽  
The Impact

Purpose: To evaluate the impact of colchicine on sympathetic denervation after acute myocardial infarction (AMI). Materials & methods: Ischemia/Reperfusion was induced in C57BL/6J male mice. Left coronary artery was ligated during 45 min followed by reperfusion. 400 μg/kg of colchicine or the placebo was administrated intraperitoneally 15 min before the reperfusion. Results: Colchicine treatment significantly improved heart rate variability index after AMI. Colchicine prevented sympathetic denervation in the remote area (p = 0.04) but not in the scar area (p = 0.70). Conclusion: These results suggest promising protective pathway of colchicine after AMI.

scholarly journals Whey Versus Casein as a Protein Source during the Weaning Period: Impact on Growth and Later Adiposity and Glucose Homeostasis in a Rat Model of Intrauterine Growth Restriction

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3399
Author(s):  
Yasaman Shahkhalili ◽  
Florence Blancher-Budin ◽  
Cathriona Monnard ◽  
Julie Moulin ◽  
José Sanchez-Garcia ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Intrauterine Growth Restriction ◽  
Early Life ◽  
Growth Restriction ◽  
Protein Source ◽  
Intrauterine Growth ◽  
Populations At Risk ◽  
Ad Libitum ◽  
The Impact

The impact of early life protein source (whey vs. casein) on short- and long-term glucose homeostasis and adiposity is unknown and was investigated in this study. At the end of the suckling period, non-IUGR (intrauterine growth restriction) and IUGR pups were separated from dams and were randomized into four groups. From age 21–49 days, non-IUGR and IUGR pups were fed ad-libitum chow or a semi-synthetic diet (20% from protein; casein or whey) and from age 50–199 days, all groups were fed ad-libitum chow. Food intake, body composition, glucose, and insulin homeostasis were assessed. Among the chow groups, IUGR had slower growth and higher fasting glucose at age 42 days, as well as higher fasting and AUC glucose at age 192 days relative to non-IUGR. The whey IUGR group had a slower growth rate and higher fasting glycemia in early life (age 21–49 days) and higher HOMA-IR later in life (age 120–122 and 190–192 days) relative to casein IUGR. This study shows the potential advantage of casein relative to whey during weaning on short term energy intake, growth, and glucose homeostasis in an IUGR model and reveals, for the first time, its long term impact on insulin sensitivity, which may have implications for later metabolic health, particularly in small-for-gestational-age populations at risk of type 2 diabetes.

scholarly journals Peanut sensitisation and allergy: influence of early life exposure to peanuts

2010 ◽  
Vol 103 (9) ◽  
pp. 1278-1286 ◽  
Author(s):  
Rachel L. Thompson ◽  
Lisa M. Miles ◽  
Joanne Lunn ◽  
Graham Devereux ◽  
Rebecca J. Dearman ◽  
...  
Keyword(s):  
Systematic Review ◽  
Early Life ◽  
Animal Studies ◽  
Human Subjects ◽  
Subsequent Development ◽  
Human Studies ◽  
Case Control Studies ◽  
Cross Sectional ◽  
Early Life Exposure ◽  
The Impact

The aim of the present systematic review was to evaluate the influence of early life exposure (maternal and childhood) to peanuts and the subsequent development of sensitisation or allergy to peanuts during childhood. Studies were identified using electronic databases and bibliography searches. Studies that assessed the impact of non-avoidance compared with avoidance or reduced quantities of peanuts or peanut products on either sensitisation or allergy to peanuts, or both outcomes, were eligible. Six human studies were identified: two randomised controlled trials, two case–control studies and two cross-sectional studies. In addition, published animal and mechanistic studies, relevant to the question of whether early life exposure to peanuts affects the subsequent development of peanut sensitisation, were reviewed narratively. Overall, the evidence reviewed was heterogeneous, and was limited in quality, for example, through lack of adjustment for potentially confounding factors. The nature of the evidence has therefore hindered the development of definitive conclusions. The systematic review of human studies and narrative expert-led reviews of animal studies do not provide clear evidence to suggest that either maternal exposure, or early or delayed introduction of peanuts in the diets of children, has an impact upon subsequent development of sensitisation or allergy to peanuts. Results from some animal studies (and limited evidence from human subjects) suggest that the dose of peanuts is an important mediator of peanut sensitisation and tolerance; low doses tend to lead to sensitisation and higher doses tend to lead to tolerance.

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