Chronic retinyl palmitate supplementation to middle‐aged Wistar rats disrupts the brain redox homeostasis and induces changes in emotional behavior

Schnorr, Carlos Eduardo; Bittencourt, Leonardo da Silva; Petiz, Lyvia Lintzmaier; Gelain, Daniel Pens; Zeidán-Chuliá, Fares; Moreira, José Cláudio Fonseca

doi:10.1002/mnfr.201400637

Cited by 11 publications

(4 citation statements)

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“…Higher or lower doses may show different effects than the ones presented here. Higher doses would probably provoke more tissue damage and inflammation as observed previously [26,27,28], and lower doses may show no effect at all, as many of the effects observed here could be considered mild. Exercise training itself is already a major source of ROS production, hence higher doses of VA were not considered for this study, as a synergistic pro-oxidant effect could take place, since excessive doses cause oxidative stress.…”

Section: Discussionsupporting

confidence: 63%

“…However, retinol has been observed to present moderate to low antioxidant activity, and VA supplementation has been associated with some adverse effects. Our group has previously shown that oral retinyl palmitate supplementation induces, in fact, a pro-oxidant environment in several tissues, including the heart, brain, and lungs of Wistar rats [26,27,28]. Moreover, it was previously described that mice fed with retinyl palmitate in low doses developed aortic valve stenosis and calcification [29].…”

Section: Introductionmentioning

confidence: 99%

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Vitamin A Oral Supplementation Induces Oxidative Stress and Suppresses IL-10 and HSP70 in Skeletal Muscle of Trained Rats

et al. 2017

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Exercise training intensity is the major variant that influences the relationship between exercise, redox balance, and immune response. Supplement intake is a common practice for oxidative stress prevention; the effects of vitamin A (VA) on exercise training are not yet described, even though this molecule exhibits antioxidant properties. We investigated the role of VA supplementation on redox and immune responses of adult Wistar rats subjected to swimming training. Animals were divided into four groups: sedentary, sedentary + VA, exercise training, and exercise training + VA. Over eight weeks, animals were submitted to intense swimming 5 times/week and a VA daily intake of 450 retinol equivalents/day. VA impaired the total serum antioxidant capacity acquired by exercise, with no change in interleukin-1β and tumor necrosis factor-α levels. In skeletal muscle, VA caused lipid peroxidation and protein damage without differences in antioxidant enzyme activities; however, Western blot analysis showed that expression of superoxide dismutase-1 was downregulated, and upregulation of superoxide dismutase-2 induced by exercise was blunted by VA. Furthermore, VA supplementation decreased anti-inflammatory interleukin-10 and heat shock protein 70 expression, important factors for positive exercise adaptations and tissue damage prevention. Our data showed that VA supplementation did not confer any antioxidative and/or protective effects, attenuating exercise-acquired benefits in the skeletal muscle.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Vitamin A Oral Supplementation Induces Oxidative Stress and Suppresses IL-10 and HSP70 in Skeletal Muscle of Trained Rats

et al. 2017

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“…Concordantly, a correlation between the activity of antioxidative enzymes (glyoxalase 1, glutathione reductase 1) and an anxiety phenotype was found in a study using six inbred mouse strains (Hovatta et al, 2005). Acute and chronic vitamin A supplementation induces anxiety-like behavior and oxidative/nitrosative stress in the adult rat hippocampus, substantia nigra and striatum (Schnorr et al, 2015). Ovariectomy causes oxidative stress in different central nervous system structures owing to depletion of antioxidant content leading to an anxiogenic profile (Da Silva Morrone et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Brain Vitamin E Deficiency During Development Is Associated With Increased Glutamate Levels and Anxiety in Adult Mice

Desrumaux

Mansuy

Lemaire

et al. 2018

Front. Behav. Neurosci.

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Vitamin E, the most important lipophilic radical scavenging antioxidant in vivo, has a pivotal role in brain. In an earlier study, we observed that adult mice with a defect in the gene encoding plasma phospholipid transfer protein (PLTP) display a moderate reduction in cerebral vitamin E levels, and exacerbated anxiety despite normal locomotion and memory functions. Here we sought to determine whether dietary vitamin E supplementation can modulate neurotransmitter levels and alleviate the increased anxiety phenotype of PLTP-deficient (PLTP−/−) mice. To address this question, a vitamin E-enriched diet was used, and two complementary approches were implemented: (i) “early supplementation”: neurotransmitter levels and anxiety were assessed in 6 months old PLTP−/− mice born from vitamin E-supplemented parents; and (ii) “late supplementation”: neurotransmitter levels and anxiety were assessed in 6 months old PLTP−/− mice fed a vitamin E-enriched diet from weaning. Our results show for the first time that an inadequate supply of vitamin E during development, due to moderate maternal vitamin E deficiency, is associated with reduced brain vitamin E levels at birth and irreversible alterations in brain glutamate levels. They also suggest this deficiency is associated with increased anxiety at adulthood. Thus, the present study leads to conclude on the importance of the micronutrient vitamin E during pregnancy.

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“…VA influences several metabolic processes (Chapman 2012), and its deficiency or excess may show very different effects. As described in the literature, higher doses would D r a f t probably increase tissue damage (Pasquali et al 2009;Gasparotto et al 2015;Schnorr et al 2015;Petiz et al 2017), and lower doses may show no effect at all. Both VA and ET are potentially pro-oxidant to tissues when applied in excess, and we wanted to avoid potential harmful effects by using higher doses of this vitamin.…”

Section: R a F Tmentioning

confidence: 91%

Role of vitamin A oral supplementation on oxidative stress and inflammatory response in the liver of trained rats

Petiz

Kunzler

Bortolin

et al. 2017

Appl. Physiol. Nutr. Metab.

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The use of dietary supplements to enhance the benefit of exercise training is a common practice. The liver is the organ where all substances are metabolized, and certain supplements have been associated with liver injury. Vitamin A (VA), a liposoluble vitamin stored in the liver, is commonly used as an antioxidant supplement. Here, we evaluated the effect of chronic VA supplementation on oxidative damage and stress parameters in trained rats. Animals were divided into the following groups: sedentary (SE), sedentary/VA (SE+VA), exercise training (ET), and exercise training/VA (ET+VA). During 8 weeks, animals were subjected to swimming (0%, 2%, 4%, 6% body weight) for 5 days/week and a VA daily intake of 450 retinol equivalents/day. Parameters were evaluated by enzymatic activity analysis, ELISA, and Western blotting. VA caused liver lipid peroxidation and protein damage in exercised rats and inhibited the increase in HSP70 expression acquired with exercise alone. The ET group showed higher levels of antioxidant enzyme activity, and VA inhibited this adaptation. Expression of the pro-inflammatory cytokines, interleukin (IL)-1β, and tumor necrosis factor-α was reduced in the ET+VA group, while the anti-inflammatory cytokine, IL-10, was increased. Western blotting showed that both exercised groups had lower levels of the receptor for advanced glycation end products, suggesting that VA did not affect this receptor. Our study demonstrated that, although VA caused oxidative damage, a controlled administration might exert anti-inflammatory effects. Further studies with higher VA doses and longer ET interventions would elucidate more the effects of the supplementation and exercise on liver parameters.

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Chronic retinyl palmitate supplementation to middle‐aged Wistar rats disrupts the brain redox homeostasis and induces changes in emotional behavior

Cited by 11 publications

References 82 publications

Vitamin A Oral Supplementation Induces Oxidative Stress and Suppresses IL-10 and HSP70 in Skeletal Muscle of Trained Rats

Vitamin A Oral Supplementation Induces Oxidative Stress and Suppresses IL-10 and HSP70 in Skeletal Muscle of Trained Rats

Brain Vitamin E Deficiency During Development Is Associated With Increased Glutamate Levels and Anxiety in Adult Mice

Role of vitamin A oral supplementation on oxidative stress and inflammatory response in the liver of trained rats

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