Hypervitaminosis A Research Articles

Hepatic Vitamin A Concentrations and Association with Infectious Causes of Child Death

To assess postmortem vitamin A (VA) concentrations in children under 5years of age and evaluate the association between VA deficiency (VAD) and infectious causes of death (CoD). In this cross-sectional study from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network, liver biopsies collected within 72hours of death were analyzed from 405 stillbirths and children under 5years in Kenya and South Africa. Total liver VA (TLVA) concentrations were quantified using ultra-performance liquid chromatography, and cutoffs of ≤0.1μmol/g, >0.1 to <0.7μmol/g, ≥0.7 to <1.0μmol/g, and ≥1.0μmol/g were used to define VAD, adequate VA status, high VA, and hypervitaminosis A, respectively. CoD were determined by expert panel review. Among 366 liver samples with viable extraction, pooled prevalences of VAD, adequacy, high VA, and hypervitaminosis were 34.2%, 51.1%, 6.0%, and 8.7%, respectively. VAD was more common among neonates compared with stillbirths, infants, or children, and among those with low birthweight (LBW), underweight, or stunting (P<.05). When adjusting for site, age, and sex, there was no significant association of VAD with increased infectious CoD (OR 1.9, 95% confidence interval [CI] 0.9, 3.8, P=.073). In stratified analyses, VA deficient boys, but not girls, had an increased risk of infectious CoD (OR 3.4, 95% CI 1.3, 10.3, P=.013). Definitive postmortem assessment of VA status identified both VAD and VA excess among children under 5years of age in Kenya and South Africa. VAD in boys was associated with increased risk of infectious mortality. Our findings may inform a transition from universal VA supplementation (VAS) to targeted strategies in certain countries.

Impact of chronic vitamin A excess on sperm morphogenesis in mice.

The increasing availability of fortified foods and supplements has caused an overconsumption of vitamin A (VA), above the recommended level. To date, the effects of chronic VA excess (VAE) on spermatogenesis remain unclear. This study aims to investigate the long-term excessive intake of VA effects on spermatogenesis in mice. Dams were initially fed a control diet (4IU/g) or a VAE diet (250IU/g), 4weeks prior to mating and during pregnancy. Dams and their male pups continued this diet regimen until the offspring reached 12weeks of age. At 12weeks of age, epididymis caudal spermatozoa and testes were collected. For histological analysis, sections were stained with periodic acid-Schiff-hematoxylin, and quantitative PCR was used to detect changes in gene expression in the testes of the VAE mice. Sperm motility and morphology were evaluated to detect the endpoint of VAE toxicity. Body weights were not significantly different between the control and VAE groups. Testicular cross-sections from the control and VAE mice contained a normal array of germ cells, and the daily sperm production was similar between the two groups. However, the percentage of seminiferous tubules in stages VII and VIII was significantly lower in the VAE mice than in the control. In addition, significant changes in the expression of genes involved in retinoid metabolism, spermatogenesis, and spermiogenesis were detected in the testes of the VAE mice. Consistently, sperm motility and head morphology were significantly impaired in the VAE mice. Our findings suggest that long-term dietary intake of VAE was able to influence both pre- and post-meiotic spermatogenesis. As a result of testicular toxicity, we demonstrated, to the best of our knowledge, for the first time that long-term VAE caused sperm-head abnormalities.

Long-term dietary intake of excessive vitamin A impairs spermatogenesis in mice.

Vitamin A and its derivatives contribute to many physiological processes, including vision, neural differentiation, and reproduction. Vitamin A deficiency causes early cessation of spermatogenesis, characterized by a marked depletion of germ cells. However, there has been no clear understanding about the role of chronic intake of vitamin A excess (VAE) in spermatogenesis. The objective of this study was to investigate whether chronic intake of VAE diet causes arrest of spermatogenesis. To examine the effects of VAE on spermatogenesis, we used ICR male mice fed with control (AIN-93G purified diet: 4 IU/g) diet or VAE (modified AIN-93G diet with VAE: 1,000 IU/g) diet for 7 weeks (from 3 to 10 weeks of age). At 10 weeks of age, the retinol concentration in the testes of VAE mice was significantly higher than that of control mice. Testicular cross sections from control mice contained a normal array of germ cells, while the seminiferous tubules from VAE mice exhibited varying degrees of testicular degeneration. Daily sperm production in VAE testes was dramatically decreased compared to that in control testes. Sperm viability, motility, and morphology were also impaired in VAE mice. Furthermore, we examined the effects of VAE on the expression of genes involved in retinoid signaling and spermatogenesis to determine the underlying molecular mechanisms. Therefore, we are the first to present results describing the long-term dietary intake of VAE impairs spermatogenesis using a mouse model.

Hepatoprotective and Immunological Functions of Nigella sativa Seed Oil against Hypervitaminosis A in Adult Male Rats

The toxic effects of excess vitamin A (VA) intake deserve increased attention. Nigella sativa (NS) seed possesses physiological and pharmacological actions and protects against toxic agents. This work investigated the availability of NS seed oil as a protective agent against the effects of hypervitaminosis A (HVA) on liver function and immunity. Fifty adult albino rats were used and divided into five groups: (G1) control; (G2) experimental HVA rats administered extreme doses (10,000 IU/kg body weight) of VA oil orally, daily for 6 weeks; (G3) rats treated with NS seed oil (800 mg/kg) orally, daily for 6 weeks; (G4) HVA rats simultaneously treated with NS seed oil at the same doses and periods; and (G5) HVA recovery group. Liver function, immunoglobulin (IgG and IgM) levels, and lysosome activity were measured in serum. HVA rats revealed marked elevations in alanine aminotransferase and aspartate aminotransferase activities. This is the first study to demonstrate that NS seed oil possesses significant hepatoprotective activity against HVA. NS seed oil was a potent inducer of IgG and IgM in rat serum either alone or with high doses of VA. These findings may be considered the initial steps of the physiological and humoral immune responses for NS seed oil against HVA, but further studies examining longer periods are needed prior to recommending the use of NS seed oil as an alternative medicine for hepatic and immune diseases.

Effects of oral administration of crude leaf extracts of Aglaia loheri Blanco and Ardisia pyramidalis (Cav.) Pers on mouse embryo morphology and maternal reproductive performance

Aglaia loheri Blanco and Ardisia pyramidalis (Cav.) Pers are both endemic plant species with a variety of bioactive compounds, but remain largely untested for their toxicity, and their effects on maternal reproductive performance and fetal morphology. Inbred ICR mice were orally administered with 10 and 5 mg/ml concentrations for A. loheri, and 10 and 1 mg/ml concentrations for A. pyramidalis from the 8th to the 15th day of pregnancy. Dissection at 16 days post coitum (dpc) showed significant differences in maternal reproductive performance, as estimated by gestation index, % dead implants, % females with resorption, % resorption and % fetus with morphological abnormalities. For A. pyramidalis, the 1 mg/ml extract + vitamin A treatment reduced maternal reproductive performance most significantly, while, for A. loheri, treatment with 10 mg/ml extract, with or without vitamin A, as well as with 5 mg/ml extract only resulted to a 100% resorption. Additionally, maternal hepatotoxicity was observed in mice treated with A. pyramidalis, while significant weight losses among mice treated with higher doses of A. loheri + vitamin A suggests toxicity and synergism with vitamin A. These results suggest that caution must be taken when taking these extracts during pregnancy due to their possible toxicity and teratogenicity. Key words: Aglaia loheri Blanco, Ardisia pyramidalis (Cav.) Pers, Meliaceae, Myrsinaceae, teratogenicity, hypervitaminosis A, reproductive performance, embryo morphology.

Effect of vitamin A acetate on urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in rats.

The effect of vitamin A acetate on the urinary bladder carcinogenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was determined in male Wistar rats. Vitamin A acetate at the dose administered induced no changes in the urinary bladder or other organs when administered without the carcinogen. However, hypervitaminosis A inhibited keratinization and squamous metaplasia in bladder lesions induced by BBN, and the incidence of transitional cell carcinoma and papilloma of the urinary bladder was significantly reduced at a dose greater than 100 IU/g diet (P less than 0.02). The present experiment suggests that for the urinary bladder epithelium of rats hypervitaminosis A reduced susceptibility to the tumorigenicity of BBN.

Vitamin (A and D)-induced premature physeal closure (hyena disease) in calves

Hypervitaminosis A and D is a potential cause of "hyena disease" in cattle, which results from premature growth-plate closure in long bones of calves. This study showed that vitamin A induced growth-plate closure if calves were given an intramuscular injection of vitamins A and D (2,000,000 IU and 300,000 IU, respectively) on the first day after birth and, in addition, vitamin A (30,000 IU/kg body weight) in a water dispersible form was added to the milk substitute daily. Gross lesions were observed in the proximal tibial growth plates of each of seven calves after 3 weeks of vitamin-A treatment. Microscopical examination showed commencing premature growth-plate closure in the proximal tibia at 2 weeks. After one week, the growth plate showed focal thinning, and there was premature endochondral ossification of columnar cartilage. Longitudinal bone growth was dramatically reduced before growth plate closure at one week (25 microns/day in a treated animal versus 136 microns/day in a control). Liver concentrations of retinol and retinyl palmitate became strikingly elevated at on week, and thereafter increased slowly until the third week. Elevation of plasma retinol and retinyl palmitate was rapid, reaching a maximum on day 10. Plasma all-trans-retinoic acid was undetectable in many samples from treated animals, but plasma concentrations of derivatives of retinoic acid (9-cis-retinoic acid, 13-cis-retinoic acid, 13-cis-4-oxoretinoic acid, and 9, 13 dicis-retinoic acid) were elevated. The vitamin-A intake required to induce growth-plate closure in calves was found to be exceedingly high. Vitamin-A toxicity must be considered as a potential cause of hyena disease, but it would seem likely that other factors also play a role.

Effects of vitamin A and/or thyroidectomy on liver microsomal enzymes and their induction in 2,3,7,8-tetrachlorodibenzo- p-dioxin-treated rats

Vitamin A and thyroid hormone status have been shown previously to alter the toxicity of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) in rats. In the present study, we have examined the effects of a vitamin A-excess and a vitamin A-deficient diet on thyroid hormone levels, on selected drug-metabolizing enzymes in liver microsomes, and on their inducibility by TCDD in male Sprague-Dawley rats. Except for a slight increase in serum T 3 levels, none of these end points was affected by feeding rats the vitamin A-deficient diet. In contrast, excess dietary vitamin A caused a decrease in serum thyroxine (T 4) and triiodothyronine (T 3) levels, although the levels of T 3 remained in the euthyroid range (60–80 ng/dl). The concentration of liver microsomal cytochromes P-450 and b 5 and the basal activity of benzo[ a]pyrene hydroxylase and 7-ethoxyresorufin O-de-ethylase were unaffected by excess dietary vitamin A. This result is consistent with our previous observation that the basal activity of these enzymes is dependent more on T 3 than on T 4 levels. Vitamin A excess markedly suppressed the activity of liver microsomal UDP-glucuronosyl transferase toward 1-naphthol. However, no such enzyme suppression was observed in thyroidectomized rats. This suggests that the suppressive effect of vitamin A on UDP-glucuronosyl transferase activity may be dependent on T 3. Neither vitamin A nor thyroid status had any major effect on the inducibility of UDP- glucuronosyl transferase and cytochrome P-450-dependent enzyme activities by TCDD. However, vitamin A and TCDD had a nearly additive effect on suppression of serum T 4. It is concluded that liver microsomal enzyme induction is not associated with the modulatory effect of vitamin A and thyroid hormones on the toxicity of TCDD.

An Assessment of Dose-related Vitamin A Toxicity

An Assessment of Dose-related Vitamin A Toxicity

Vitamin A toxicity is an increasing problem

Vitamin A toxicity is an increasing problem

Hypercalcemia due to hypervitaminosis A

Hypercalcemia due to hypervitaminosis A

Decreased fixation of sulphate by chondrocytes in hypervitaminosis A

The Journal of Pathology and BacteriologyVolume 83, Issue 2 p. 347-355 Article Decreased fixation of sulphate by chondrocytes in hypervitaminosis A T. F. McElligott, T. F. McElligott Department of Pathology, University of SheffieldSearch for more papers by this author T. F. McElligott, T. F. McElligott Department of Pathology, University of SheffieldSearch for more papers by this author First published: April 1962 https://doi.org/10.1002/path.1700830203Citations: 18AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume83, Issue2April 1962Pages 347-355 RelatedInformation