Teratogenicity, Tissue Distribution, and Metabolism of the retro-Retinoids, 14-Hydroxy-4,14-retro-retinol and Anhydroretinol, in the C57BL/6J Mouse

Mao, Gloria E.; Collins, Michael D.; Derguini, Fadila

doi:10.1006/taap.1999.8828

Cited by 11 publications

(4 citation statements)

References 46 publications

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“…Furthermore, the entire live adult (mother) in this group had dead fetuses except one of them was found alive, this finding is in agreement with Ross, (2002), their result indicated that RA is being toxic and leading to the spontaneous abortion. Result of Mao et al, (2000) are found in agreement with the result of the recent study, their results indicated that retinol dosage of 20 or 40 mg/kg did not increase embryo lethality or alter litter size, while the dosage of 60mg/kg of retinol increased in embryo lethality, and dosage of 80mg/kg caused high embryo lethality (92.5%). In 2016, Aguwa et al also reported treatment with an overdose of vitamin A (400 and 500 mg/kg) caused spontaneous abortion and death of the fetuses.…”

Section: Discussionsupporting

confidence: 91%

The Effects of Different Concentrations of Retinoic Acid on the Histological Structure of Liver of Adult Albino Female Mice and Their Prenatal Fetuses

2020

JBAH

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Retinoic acid (RA) an active metabolite of vitamin A, plays essential signaling roles in mammalian embryonic development and adult homeostasis through concentration-dependent activity but in excess, RA is teratogenic. The present study was designed to evaluate the harmful effect of RA on the: liver tissues of the adult pregnant female albino mice and their prenatal fetuses and adult morphological and behavior changes. Forty-five pregnant adult female albino mice were divided into three groups (n=15 for each group). Group I, the control group orally received 0.1ml of olive oil. Group II and III received 25 and 50mg RA/kg B.W. respectively. RA was dissolved in 0.1ml of olive oil and orally given on 7 th , 8 th , and 9 th days of pregnancy. On the 18 th day of gestation, these females were sacrificed and the liver from mother and their prenatal were removed, weighed, and prepared for histological study. The RA treated adult group exhibited behavior changes including general fatigue and loss of appetite, in addition to the morphological changes which included weight loss, change in normal red eye color towards black, and redness in the mouth and chin area associated with loss of hair (fur) around this area. These observations were showed to be more severe in the 50 mg RA group. The results showed that treatment with 25 and 50mg RA caused no significant decrease in the adult liver weight, while in their prenatal fetuses 50mg RA caused a higher significant decrease in the liver weight, but 25 mg RA caused no significant effects on this weight. Treated with 50mg/kg RA caused a highly significant increase in the number of aborted and dead fetuses as compared with other groups. The results of the histological study showed that treatment with both concentrations of RA caused several degrees of the liver damage with disrupted the normal architecture pattern along with hepatocellular steatosis, hypertrophy, and inflammation. In conclusions, RA caused variable degrees of degeneration and destruction of the liver tissues of adult female (mother) and their prenatal. The most important effects of RA are causing hepatocellular steatosis, hypertrophy, and inflammation, and when RA giving during the critical periods of embryonic development, caused harmful effects on the developing liver, therefore treatment with RA should be avoided at any stage of gestation.

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Section: Discussionsupporting

confidence: 91%

The Effects of Different Concentrations of Retinoic Acid on the Histological Structure of Liver of Adult Albino Female Mice and Their Prenatal Fetuses

2020

JBAH

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“…Retinol circulates in plasma at a constant concentration of 1 to 2 M, matching the effective dose of 2 M required for PKC coactivation. Other retinoids (e.g., retinoic acid) circulate at concentrations 3 orders of magnitude lower or not at all (anhydroretinol and retinal) (40). Further evidence that retinol is active in the PKC␦ signal path, regardless of whether other retinoids can mimic retinol in pharmacological experiments, was the responses of isolated mitochondria in short-term experiments when reaction times were too brief to permit appreciable metabolism of retinol.…”

Section: Discussionmentioning

confidence: 99%

Control of oxidative phosphorylation by vitamin A illuminates a fundamental role in mitochondrial energy homoeostasis

et al. 2009

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The physiology of two metabolites of vitamin A is understood in substantial detail: retinaldehyde functions as the universal chromophore in the vertebrate and invertebrate eye; retinoic acid regulates a set of vertebrate transcription factors, the retinoic acid receptor superfamily. The third member of this retinoid triumvirate is retinol. While functioning as the precursor of retinaldehyde and retinoic acid, a growing body of evidence suggests a far more fundamental role for retinol in signal transduction. Here we show that retinol is essential for the metabolic fitness of mitochondria. When cells were deprived of retinol, respiration and ATP synthesis defaulted to basal levels. They recovered to significantly higher energy output as soon as retinol was restored to physiological concentration, without the need for metabolic conversion to other retinoids. Retinol emerged as an essential cofactor of protein kinase Cdelta (PKCdelta), without which this enzyme failed to be activated in mitochondria. Furthermore, retinol needed to physically bind PKCdelta, because mutation of the retinol binding site rendered PKCdelta unresponsive to Rol, while retaining responsiveness to phorbol ester. The PKCdelta/retinol complex signaled the pyruvate dehydrogenase complex for enhanced flux of pyruvate into the Krebs cycle. The baseline response was reduced in vitamin A-deficient lecithin:retinol acyl transferase-knockout mice, but this was corrected within 3 h by intraperitoneal injection of vitamin A; this suggests that vitamin A is physiologically important. These results illuminate a hitherto unsuspected role of vitamin A in mitochondrial bioenergetics of mammals, acting as a nutritional sensor. As such, retinol is of fundamental importance for energy homeostasis. The data provide a mechanistic explanation to the nearly 100-yr-old question of why vitamin A deficiency causes so many pathologies that are independent of retinoic acid action.

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“…After mixing and centrifugation, the supernatant is injected directly into the HPLC. This procedure, or slight modifications of it, was used by others for hepatic tissue (Decker and Zimmerman, 1995), mouse liver (Mao et al, 2000), and whole mouse embryos.…”

Section: Extractionmentioning

confidence: 99%

Methods for detecting and identifying retinoids in tissue

Gundersen

2006

J. Neurobiol.

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Methods for retinoid analysis in tissue include direct spectrophotometry or fluorometry and retinoid responsive reporter constructs in the form of cell reporter assays or transgenic reporter animals, but chromatographic methods dominate and posses several superior features in quantitative analysis. The multitude of extraction protocols used can coarsely be divided into manual liquid-liquid extraction protocols and semi-or fully automated solid phase extraction-based protocols.Liquid chromatographic separation in reversed phase dominates although normal phase is also used. Detection is mainly performed with UV detectors although electrochemical and fluorescence detection is also used. Mass spectrometry in combination with LC is more often used in retinoid analysis and is likely to dominate in the future.

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Teratogenicity, Tissue Distribution, and Metabolism of the retro-Retinoids, 14-Hydroxy-4,14-retro-retinol and Anhydroretinol, in the C57BL/6J Mouse

Cited by 11 publications

References 46 publications

The Effects of Different Concentrations of Retinoic Acid on the Histological Structure of Liver of Adult Albino Female Mice and Their Prenatal Fetuses

The Effects of Different Concentrations of Retinoic Acid on the Histological Structure of Liver of Adult Albino Female Mice and Their Prenatal Fetuses

Control of oxidative phosphorylation by vitamin A illuminates a fundamental role in mitochondrial energy homoeostasis

Methods for detecting and identifying retinoids in tissue

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