Liver damage with reversible portal hypertension from vitamin A intoxication: demonstration of Ito cells.

Guarascio, P.; Portmann, Bernard; Visco, G; Williams, Roy G.

doi:10.1136/jcp.36.7.769

Cited by 27 publications

(15 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A retrospective evaluation of the hyperplasia of Ito cells [14][15][16] in liver tissue was performed in 18 liver biopsies of HD patients obtained because of persistent biochemical evidence of liver dam age. 8 of them belonged to patients included in the prospective investigation.…”

Section: Methodsmentioning

confidence: 99%

“…The development of liver injury which occasionally leads to portal hypertension and ascites has been de scribed as a consequence of the intake of large amounts of VA in subjects with normal renal function [14,16,20,21], An important role in the pathogenesis of this complication has been ascribed to the so-called Ito cells [14][15][16], also known as lipocytes or VA storage cells [14], These cells have many cytoplasmic lipid droplets ( fig. 1) and differ from other sinusoidal cells in two important points: (a) they have no phagocytic capacity, (b) they are located in the perisinusoidal space of Disse.…”

Section: Other Parametersmentioning

confidence: 99%

“…33 on 10,000 IU/day and 5 patients with no VA intake. (table II) 4 months after the withdrawal of MP containing VA. the plasma levels of VA were reassessed in 54 out of the 71 patients initially studied (16 …”

Section: Plasma Levels O F Vamentioning

confidence: 99%

See 2 more Smart Citations

Implications of Hypervitaminosis A on the Calcium-Phosphate Metabolism and on Blood Lipids in Hemodialysis

Praga¹,

Rubio

Morales³

et al. 1987

Am J Nephrol

View full text Add to dashboard Cite

Serum levels of vitamin A (VA) were measured in 71 hemodialysis (HD) patients and in 30 normal controls. 65 of the 71 patients were taking multivitamin preparations (MP) containing VA. The HD patients had significantly greater values: 7.81 ± 2.86 μmol/l (224 ± 82 μg/dl) versus 3.97 ± 0.97 μmol/l (114 ± 28 μg/dl; p < 0.0005); those taking MP with large doses of VA showed the highest levels. Patients were divided as having normal (group I, n = 21) or elevated (group II, n ≈ 50) serum levels of VA. Patients of group II had higher levels of serum calcium (Ca) and lower of serum phosphate (P) and PTH than those of group I. Four months after the withdrawal of oral VA, the serum levels of VA and Ca fell significantly in group II, while the serum P increased. On the contrary, in group I serum levels of VA, Ca and P remained unchanged. Serum triglycerides (TG) were significantly higher in group II but did not change after the withdrawal of VA. No differences between both groups of patients were observed for age, time on HD, residual diuresis, residual renal function, serum levels of cholesterol (CL) or anemia. A retrospective study of 18 hepatic biopsies of HD patients disclosed hypeφlasia of Ito cells (VA-storaging cells) in 7 of them. These 7 biopsies belonged to patients who had taken large amounts of oral VA. Our data indicate that prolonged VA intake in HD patients is followed by an increase of serum CA, a decrease of serum P and PTH and a hepatic accumulation of VA. Since we observed a correlation between oral intake of VA and serum levels of VA, it is necessary to know the VA content of MP administered to HD patients.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Other Parametersmentioning

confidence: 99%

See 1 more Smart Citation

Implications of Hypervitaminosis A on the Calcium-Phosphate Metabolism and on Blood Lipids in Hemodialysis

Praga¹,

Rubio

Morales³

et al. 1987

Am J Nephrol

View full text Add to dashboard Cite

show abstract

“…The clinical effective dose for vitamin A administration in the case of degenerative eye diseases such as retinitis pigmentosa (15,-000 IU/day) is below the maximal recommended dose (25,-000 IU/day) and was shown to be well tolerated after 12 years of treatment (129,130). In the few documented cases, recovery from acute retinoid toxicity is rapid once intake is reduced (131,132). Chronic effects are manifested as drying, ulceration and desquamation of the skin, anorexia, anemia, and bone loss.…”

Section: Retinol Toxicity and The Side Effects Associated With Retinomentioning

confidence: 99%

“…Liver damage leading to fibrosis and hepatic stellate cell activation are both seen in patients affected by hypervitaminosis A (133). Upon activation, hepatic stellate cells lose their capacity to store retinyl esters and secrete collagen, leading to cirrhosis (132,134). Oxidation of retinol generates RA, which stimulates osteoclast formation and activity leading to bone resorption and hypercalcemia (135,136).…”

Section: Retinol Toxicity and The Side Effects Associated With Retinomentioning

confidence: 99%

Delivery of Retinoid-Based Therapies To Target Tissues

et al. 2007

View full text Add to dashboard Cite

Through its various metabolites, vitamin A controls essential physiological functions. Both naturally occurring metabolites and novel retinoid analogues have shown effectiveness in many clinical settings that include skin diseases and cancer, and in animal models of human conditions affecting vision.In this review, we analyze several potential retinoid-based therapies from the point of view of drug metabolism and transport to target tissues. We focus on the endogenous factors that affect the absorption, transport, and metabolism of retinoids by taking into account data obtained from the analysis of animal models that lack the enzymes or proteins involved in the storage and absorption of retinoids. We also discuss findings of toxicity associated with retinoids in an effort to improve the outcome of retinoid-based therapies. In this context, we review evidence that esterification of retinol and retinol-based drugs within target tissues provides one of the most efficient means to improve the absorption and to reduce the toxicity associated with pharmacological doses of retinoids. Future retinoid-based therapeutic strategies could involve targeted delivery mechanisms leading to lower toxicity and improved effectiveness of retinoids.Vitamin A, retinol, plays essential roles in many biological processes including vision, immunity, growth, development, and cellular differentiation. The various functions of vitamin A are carried out by several known physiologically active metabolites including 11-cis-retinal, the visual chromophore (1), and all-trans-retinoic acid (RA 1 ), which controls gene expression through the RA receptor (RAR) (2,3). Other retinol metabolites that have shown biological activities in vitro are the 9-cis-isomer of RA, which activates both retinoid X receptors (RXRs) and RARs (4), and the retro-retinoids, anhydroretinol (AR), and 14-hydroxy-4,14-retro-retinol (14-HRR), which are involved in the regulation of lymphocyte proliferation (5-7). Alltrans-13,14-dihydroxy-retinol was shown to have activity comparable to that of 14-HRR in supporting the proliferation of promyelocytic HL-60 cells and in the activation of T cells (8). The conversion of all-trans-retinol to all-trans-13,14-dihydroretinol by the recently described † This research was supported in part by U.S. Public Health Service Grants EY01730, EY015399, and EY08061 from the National Eye Institute, National Institutes of Health, Bethesda, MD (to K.P.) and Grant DK068437 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (to W.S.B.). * To whom correspondence should be addressed. Phone: 216-368-1284. Fax: 216-368-1300. E-mail: ram50@case.edu. ‡ Case Western Reserve University. § Institute of Human Nutrition, Columbia University. || Department of Medicine, Columbia University.1 Abbreviations: A2E, pyridinium bis-retinoid; ADH, medium-chain alcohol dehydrogenases; ADRP, autosomal dominant retinitis pigmentosa; apoE, apolipoprotein E; AR, anhydroretinol; ARAT, acyl-CoA-retin...

show abstract

Safety of Antioxidant Vitamins

Meyers

Maloley²,

Weeks³

1996

Arch Intern Med

116

View full text Add to dashboard Cite

As a result of the many scientific and popular press reports of the benefits of antioxidant vitamins (vitamin A, beta-carotene, vitamin E, and ascorbic acid), it is estimated that 40% of the US population is consuming vitamin supplements. The efficacy of these supplements is not yet proved, and some have questioned their safety. Approximately 10 to 15 cases of vitamin A toxic reactions are reported per year in the United States, usually at doses greater than 100,000 IU/d. No adverse effects have been reported for beta-carotene. The frequency of vitamin E toxic reactions is not well delineated, but case reports are few at dosages less than 3200 mg/d. Ascorbic acid toxic reactions are rare at dosages less than 4 g/d. Despite a lack of clinical trial data, it seems that antioxidant vitamins are safe, although prudence might dictate their avoidance by women of childbearing potential, persons with liver disease or renal dysfunction, and those taking certain medications or undergoing specific laboratory tests.

show abstract

Liver damage with reversible portal hypertension from vitamin A intoxication: demonstration of Ito cells.

Cited by 27 publications

References 19 publications

Implications of Hypervitaminosis A on the Calcium-Phosphate Metabolism and on Blood Lipids in Hemodialysis

Implications of Hypervitaminosis A on the Calcium-Phosphate Metabolism and on Blood Lipids in Hemodialysis

Delivery of Retinoid-Based Therapies To Target Tissues

Safety of Antioxidant Vitamins

Contact Info

Product

Resources

About