Toxicity of Retinoids in Humans and Animals

Howard, W. Brian; Willhite, Calvin C.

doi:10.3109/15569548609012706

Cited by 50 publications

(16 citation statements)

References 8 publications

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“…?_), has been utilized for the treatment of dermatologic disorders since 1982 (8). Retinoic acids have been reported to produce multiple abnormalities including limb deformities, heart de fects, and facial malformations in mammals and have similar teratogenic effects in humans (9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

Effect of Retinoids on Proliferation of Human Embryonic Palatal Mesenchymal Cells in Culture

Watanabe

Willis

Pratt

1990

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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mentioning

confidence: 99%

Effect of Retinoids on Proliferation of Human Embryonic Palatal Mesenchymal Cells in Culture

Watanabe

Willis

Pratt

1990

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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“…The toxic ef fects of orally administered 13cRA are: chelitis, headache, xerosis, anorexia, dry mucous membranes, nausea and vomiting, and to a lesser degree visual disturbance, pruritis, and hair thinning [7,8], Although topical tRA therapy is regarded safe [9,11,12], orally administered tRA, 13cRA and etretinate are highly teratogenic. Thus, these drugs are not prescribed to women who are pregnant or might become pregnant during therapy [1,[13][14][15][16][17], All-/ram-retinoyl (3-glucuronide (RAG), first identified as a biliary metabolite of vita min A [18,19], occurs endogenously in hu man blood [20], RAG and its 13-m-isomer have been identified as major biliary metabo lites of RA in the rat [21][22][23], Following administration of all-tram, 13-d,v-and 9-cis-RA. their respective p-glucuronides have been characterized as major plasma metabolites in the monkey [24][25][26], in the rat [27,28], in the mouse [27,29], in the rabbit [30], and in the human [20,25], RAG, like RA, shows high biological activity in enhancing the growth of vitamin A-deficient rats [31,32] and in induc ing the differentiation of HL-60 [33][34][35][36] and GBA-HAN-1C cells [37], In contrast.…”

mentioning

confidence: 99%

Percutaneous Absorption, Excretion and Metabolism of All-<i>trans</i>-Retinoyl β-Glucuronide and of AII-<i>trans</i>-Retinoic Acid in the Rat

Barua

Olson²

1996

Skin Pharmacol Physiol

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The purpose of these studies was to compare directly the percutaneous absorption, excretion and metabolism of all-trans-retinoyl Β-glucuronide (RAG), a nontoxic retinoid, with all-trans-retinoic acid (RA) in the rat. Previously, it was demonstrated that topical treatment of human acne with either RAG or RA in cream resulted in a significant reduction of lesions. Whereas 0.1 % RA showed adverse effects, concentrations of RAG up to 2.4% did not cause any adverse reactions. In the present studies, radiolabeled RAG or RA, dispersed in a water-based cream, was applied to the shaved dorsal skin of vitamin A-sufficient rats. Both RAG and RA were absorbed from the skin in a similar way. In both cases, radioactivity peaked in the plasma within 2-4 h and within the liver at 4-12 h. During a 7-day period, the overall excretion of radioactivity derived from RA and RAG in the feces and urine were similar, e.g. 17 and 12%, respectively. It is concluded that: (1)the transport, metabolism and excretion of topically applied radioactive RA and RAG are similar, although not identical, in the rat and (2) the toxic skin manifestations induced by RA but not by RAG cannot be attributed to major differences in their overall absorption, metabolism and excretion.

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“…Retinyl esters, because of their amphipathic characteristics, are believed to be more injurious to the membranes via detergent disruption than retinol bound to RBP [15]. It is generally thought that liver vitamin A measure is an indicative of vitamin A toxicity.…”

Section: Toxicological Implications Of Elevated Hepatic Storage Of VImentioning

confidence: 99%

“…Indeed in North American diets there is an abundance of pre-formed vitamin A containing foods including organ meat, beef, eggs, fish oil as well as fortified foods like margarine, non fat milk, breakfast cereal, and some snack foods. In addition, the use of multivitamins/mineral supplements, usually providing 5000 to 10,000 IU (1500-3000 micrograms vitamin A) as retinol or retinyl palmitate (1) is increasingly becoming popular among older population because of their claims being beneficial for many age-related conditions, such as eye health and reduced risk for bladder cancer [10], cataract [11], inflammatory conditions [12,13], immunity [14] and skin health [15]. In view of the fact that the turnover rate of vitamin A is slow due to its lipid solubility, detary and supplemental abundance in North American diet and possibly its diminished physiological requirements in old age, may account for its accumulation in the liver over a period of one's life time.…”

Section: Age-associated Changes In Plasma and Liver Levels Of Vitamin Amentioning

confidence: 99%

Significance of Vitamin A (Retinol) in Ageing

Basu¹

2011

TONUTRAJ

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Summary:In recent years, studies involving animal models, case reports, and some epidemiological studies have indicated that an accumulation of vitamin A in the liver is linked to low bone mineral content, fracture risk, and hence osteoporosis. While vitamin A in its physiological level acts as an inducer of bone matrix protein (osteocalcin) and matrix GLA protein in the osteoblast cells (bone formation), excess reinoic acid (a metabolic product of vitamin A) supresses osteoblastic activity and stimulates osteoclast formation (bone degradation). There also appear to have an antagonistic or synergistic interactions between vitamins A and D, influencing bone metabolosm; such effects are dose related. These effects could be of concern, especially for the older persons, because of the age-associated cumulation of vitamin A in the liver. The vitamin A status in elderly population, however, has not been as well documented as in an earlier age. In effect, the Food and Nutrition Board of National Academy's Institute of Medicine has not made any differenciation in it's recommendation for the Dietary Reference Intake (DRI) of vitamin A between 14 years and >70 years old individuals. This report will delineate the ageing differences in metabolic availability of vitamin A and that such differences are independent of its intake. The report will also attempt to formulate a hypothesis that in old age, deficiency of vitamin A is not a concern but its potential toxicity involving bone.

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Toxicity of Retinoids in Humans and Animals

Cited by 50 publications

References 8 publications

Effect of Retinoids on Proliferation of Human Embryonic Palatal Mesenchymal Cells in Culture

Effect of Retinoids on Proliferation of Human Embryonic Palatal Mesenchymal Cells in Culture

Percutaneous Absorption, Excretion and Metabolism of All-<i>trans</i>-Retinoyl β-Glucuronide and of AII-<i>trans</i>-Retinoic Acid in the Rat

Significance of Vitamin A (Retinol) in Ageing

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