Vitamin A cycle byproducts impede dark adaptation.

Impaired dark adaptation (DA), a defect in the ability to adjust to dimly lit settings, is a universal hallmark of aging. However, the mechanisms responsible for impaired DA are poorly understood. Vitamin A byproducts, such as vitamin A dimers, are small molecules that form in the retina during the vitamin A cycle. We show that later in life, in the human eye, these byproducts reach levels commensurate with those of vitamin A. In mice, selectively inhibiting the formation of these byproducts, with the investigational drug C20D3-vitamin A, results in faster DA. In contrast, acutely increasing these ocular byproducts through exogenous delivery leads to slower DA, with otherwise preserved retinal function and morphology. Our findings reveal that vitamin A cycle byproducts alone are sufficient to cause delays in DA and suggest that they may contribute to universal age-related DA impairment. Our data further indicate that the age-related decline in DA may be tractable to pharmacological intervention by C20D3-vitamin A.

FATP1 inhibits 11-cis retinol formation via interaction with the visual cycle retinoid isomerase RPE65 and lecithin:retinol acyltransferase.

The isomerization of all-trans retinol (vitamin A) to 11-cis retinol in the retinal pigment epithelium (RPE) is a key step in the visual process for the regeneration of the visual pigment chromophore, 11-cis retinal. LRAT and RPE65 are recognized as the minimal isomerase catalytic components. However, regulators of this rate-limiting step are not fully identified and could account for the phenotypic variability associated with inherited retinal degeneration (RD) caused by mutations in the RPE65 gene. To identify new RPE65 partners, we screened a porcine RPE mRNA library using a yeast two-hybrid assay with full-length human RPE65. One identified clone (here named FATP1c), containing the cytosolic C-terminal sequence from the fatty acid transport protein 1 (FATP1 or SLC27A1, solute carrier family 27 member 1), was demonstrated to interact dose-dependently with the native RPE65 and with LRAT. Furthermore, these interacting proteins colocalize in the RPE. Cellular reconstitution of human interacting proteins shows that FATP1 markedly inhibits 11-cis retinol production by acting on the production of all-trans retinyl esters and the isomerase activity of RPE65. The identification of this new visual cycle inhibitory component in RPE may contribute to further understanding of retinal pathogenesis.

Ameliorated Effects of (-)-Epigallocatechin Gallate Against Toxicity Induced by Vanadium in the Kidneys of Wistar Rats.

The aim of the study was to assess the protective effect of (-)-epigallocatechin gallate (EGCG), a flavonoid abundant in green tea, against ammonium metavanadate (AMV)-induced oxidative stress in male Wistar rats. Four groups of animals have been used, a control group and three test groups. In the first test group, AMV was intra-peritoneally (i.p) injected daily (5 mg/kg body weight for five consecutive days). The second test group of animals was also injected daily with EGCG (5 mg/kg body weight) during the same period. However, the third test group was i.p. injected with both AMV and EGCG (5 mg/kg body weight for five consecutive days). When given alone, AMV induced an oxidative stress evidenced by an increase of lipid peroxidation levels (expressed as TBARS concentration) in kidney. In these animals, activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were significantly decreased, suggesting significant reduction of the antioxidant defense system at the cell level. Kidney histological sections, showed glomerular hypertrophy and tubular dilatation. In AMV-treated animals receiving EGCG, the oxidative stress was much less pronounced and activities of antioxidant enzymes were kept close to control values. Histopathological changes were less prominent. Our results confirm that green tea and other sources of flavonoids might confer a strong protection against ammonium metavanadate-induced oxidative stress.

Identification of compounds that modulate retinol signaling using a cell-based qHTS assay.

In vertebrates, the retinol (vitamin A) signaling pathway (RSP) controls the biosynthesis and catabolism of all-trans retinoic acid (atRA), which regulates transcription of genes essential for embryonic development. Chemicals that interfere with the RSP to cause abnormal intracellular levels of atRA are potential developmental toxicants. To assess chemicals for the ability to interfere with retinol signaling, we have developed a cell-based RARE (Retinoic Acid Response Element) reporter gene assay to identify RSP disruptors. To validate this assay in a quantitative high-throughput screening (qHTS) platform, we screened the Library of Pharmacologically Active Compounds (LOPAC) in both agonist and antagonist modes. The screens detected known RSP agonists, demonstrating assay reliability, and also identified novel RSP agonists including kenpaullone, niclosamide, PD98059 and SU4312, and RSP antagonists including Bay 11-7085, LY294002, 3,4-Methylenedioxy-ß-nitrostyrene, and topoisomerase inhibitors (camptothecin, topotecan, amsacrine hydrochloride, and idarubicin). When evaluated in the P19 pluripotent cell, these compounds were found to affect the expression of the Hoxa1 gene that is essential for embryo body patterning. These results show that the RARE assay is an effective qHTS approach for screening large compound libraries to identify chemicals that have the potential to adversely affect embryonic development through interference with retinol signaling.

Oxidative stress-independent depletion of epidermal vitamin A by UVA.

In hairless mice, epidermal vitamin A (retinol and retinyl esters) is strongly decreased following a single exposure to UVB. Here, using the same mouse model, we studied the effects of UVA on epidermal vitamin A content, lipid peroxidation, and CRBP-I expression, as well as the putative prevention of vitamin A depletion or lipid peroxidation by topical alpha-tocopherol. An acute exposure to UVA completely depleted epidermal vitamin A with EC50 of 0.25 and 0.5 J per cm2 for retinyl esters and retinol, respectively; these values were 0.1 J per cm2 for both retinoids under UVB exposure. CRBP-I expression was increased 2-fold 8 h following UVA exposure (10 J per cm2), and this increase persisted for at least 16 h. A single UVA exposure induced a concentration-dependent epidermal lipid peroxidation (EC50 = 3.5 J per cm2) giving rise to 55.4 +/- 4.2 nmol lipid peroxides per g at 20 J per cm2, whereas UVB, up to 1 J per cm2, did not increase the basal concentration of 6.7 +/- 0.9 nmol lipid peroxides per g. On the other hand, topical menadione induced a concentration-dependent lipid peroxidation, but did not affect vitamin A content. Pretreatment with alpha-tocopherol (i) did not inhibit UV-induced vitamin A depletion, (ii) completely inhibited the increased lipid peroxidation induced by UVA or menadione, and (iii) accelerated reconstitution of epidermal vitamin A after UVB but not UVA induced depletion. Thus acute UVA induced both epidermal vitamin A depletion and lipid peroxidation, UVB induced only vitamin A depletion, and menadione induced only a lipid peroxidation; topical alpha-tocopherol prevented lipid peroxidation but not vitamin A depletion. These observations indicate (i) that CRBP-I neither provides protection to UVB- and UVA-induced epidermal vitamin A depletion, nor interferes significantly with reconstitution, and (ii) that the UV-induced vitamin A depletion and lipid peroxidation in mouse epidermis are unrelated processes. UV light does not destroy epidermal vitamin A through an oxidative stress but probably by a photochemical reaction in which UV radiations at about 325 nm give the corresponding activation energy.

The effects of vitamin A on insulin release and glucose oxidation in isolated rat islets.

We tested the effects of vitamin A, a membrane surface-active agent, on glucose (16.7 mM)-induced biphasic insulin release from collagenase-isolated rat islets. Also, efforts were made to correlate the effects of vitamin A with glucose oxidation. Vitamin A (10(-4) M) inhibited first- and second phase insulin release; 10(-5) M vitamin A inhibited second phase release only and to a lesser extent than that observed with 10(-4) M vitamin A; and 10(-6) M vitamin A had no effect. Vitamin A (10(-7) M) stimulated biphasic insulin release. Exposure to high glucose (27.8 mM) overcame the effects of 10(-4) M vitamin A on first phase release, but not on second phase release of insulin. Exposure to 10(-5) M hydrocortisone opposed the effects of 10(-4) M vitamin A on both phases of insulin release. Vitamin A (10(-4) and 10(-5) M) inhibited glucose oxidation by islets, as measured by the production of 14CO2 from [14C]glucose. The effects of vitamin A on insulin release were dissociated in part from those effects on glucose oxidation, in that hydrocortisone opposed the effect of vitamin A on insulin release but not on glucose oxidation. The effects of vitamin A on insulin secretion can best be explained by the interaction of vitamin A at multiple sites affecting the membrane and intracellular glucose oxidation.

Modulation of tumor promotion in mouse skin by the food additive citral (3,7-dimethyl-2,6-octadienal).

Citral inhibits the formation of retinoic acid from retinol in mouse epidermis. Since skin-carcinogenesis is sensitive to retinoid status, and retinoic acid may be the active form of vitamin A in the epidermis, citral was tested for its ability to modulate tumor promotion in a two-stage skin-carcinogenesis study in hairless mice. The dorsal skins of female skh/hr1 mice were initiated with 0.1 mumol dimethylbenzanthracene, and tumors were promoted by twice-weekly application of 10 nmol of tetradecanoylphorbol-13-acetate (TPA) for 20 weeks. Prior to each TPA application groups were dosed with 0, 1 mumol, or 10 mumol citral. Citral had a dose-dependent inhibitory effect on tumor-production in the TPA promoted groups. At 10 weeks of promotion the percentage of mice with tumors were 88%, 72% and 60%, for the 0, 1 and 10 mumol citral treated groups, and the numbers (mean +/- S.D.) of tumors per affected animal were 7.3 +/- 6.6, 3.9 +/- 4.2, and 3.7 +/- 3.5, respectively. At 15 weeks of promotion the tumor incidence was 96%, 96% and 84%, respectively, and the number of tumors per affected animal were 9.5 +/- 6.8, 7.2 +/- 4.6 and 4.5 +/- 3.3, respectively. Again the affected mice in the high dose citral group had significantly fewer tumors. When the study was terminated at 20 weeks of promotion all mice had at least one tumor, but the number of tumors per affected mouse were lower in the citral treated groups. These findings concur with the proposal that there is a retinoid requirement for skin tumor promotion, and establishes that anti-retinoids have potential uses as modulators of carcinogenesis.

Mitochondrial activity and cytotoxicity of vitamin A (retinol) in yeast and human cell cultures. Protective effect of antioxidants.

Vitamin A inhibited the growth of yeast and human cells in a dose-dependent but selective manner in cultures utilizing a non-fermentable carbon and energy source. At sub-inhibitory concentrations in yeast cultures (approximately 100 micrograms/mL), the vitamin had a stimulatory effect on the mitochondrial system, foreshortening the lag phase in the adaptation to non-fermentable substrate. At inhibitory concentrations, vitamin A depressed mitochondrial protein synthesis relative to cytoplasmic protein synthesis and induced the mitochondrial mutation petite but had little or no mutagenicity with respect to nuclear genes at the concentrations used. The vitamin showed a dose-dependent cytotoxicity (lethality) in both yeast and human cells. All of these deleterious effects were overcome to a large extent by the presence of antioxidants implicating free-radical metabolites in much of the toxicity.

Immunocytochemistry of epithelial markers in citral-induced prostate hyperplasia in rats.

Immunocytochemical characterization of several epithelial markers using the PAP technique was analyzed during different stages of induced prostatic hyperplasia in rats. Intact adolescent rats (42 days old) were treated with citral (3,7 dimethyl-2,6 octadienal) for 10, 30 and 100 days and their ventral prostate compared to untreated, matched-age animals. Among the epithelial markers studied the prostatic specific acid phosphatase was present in hyperplastic prostates of rats. The immunoreaction showed a fair correlation with the severity of lesion and duration of treatment. The prostatic specific antigen showed equally immunoreactive in both control and treated rats. The hyperplastic and normal rat prostates did not show immunoreactivity towards the other epithelial cell markers such as epithelial membrane antigen, carcinoembrionic antingen and alpha-fetoprotein antisera. It is concluded that prostatic specific acid phosphatase, and to a lesser extent prostatic specific antigen, might represent valuable markers for comparative studies of prostatic hyperplasia in rodents.

Prevention of vitamin A teratogenesis by phytol or phytanic acid results from reduced metabolism of retinol to the teratogenic metabolite, all-trans-retinoic acid.

Previous studies in our laboratory showed a synergistic interaction of synthetic ligands selective for the retinoid receptors RAR and RXR in regard to teratogenic effects produced in mice (M. M. Elmazar et al., 2001, TOXICOL: Appl. Pharmacol. 170, 2-9). In the present study the influence of phytol and phytanic acid (a RXR-selective ligand) on the teratogenicity of retinol and the RAR-selective ligand all-trans-retinoic acid was investigated by coadministration experiments on day 8.25 of gestation in NMRI mice. Phytol and phytanic acid, noneffective when administered alone, did not potentiate the teratogenicity induced by retinol or all-trans-retinoic acid. On the contrary, phytol and phytanic acid greatly reduced retinol-induced teratogenic effects (ear anotia, tail defects, exencephaly). The effect of phytol on all-trans-retinoic acid teratogenesis was limited (only resorptions and tail defects were reduced). Pharmacokinetic studies in nonpregnant animals revealed that phytol coadministration with retinol reduced plasma levels of retinol and retinyl esters, and drastically reduced the levels of the teratogenic retinol metabolite, all-trans-retinoic acid. Phytanic acid also reduced the oxidative metabolism and teratogenic effects of retinol. These results indicate that phytol and phytanic acid did not synergize with retinol and all-trans-retinoic acid in our mouse teratogenesis model. Instead, phytol and phytanic acid effectively blocked the teratogenic effects of retinol by drastically reducing the metabolic production of all-trans-retinoic acid. Phytol and phytanic acid may be useful for the prevention of vitamin A teratogenicity.

In vitro antimalarial activity of retinoids and the influence of selective retinoic acid receptor antagonists.

Retinol (vitamin A alcohol) may have a beneficial role in the host response to malaria in humans and previously published data have suggested that it has a direct inhibitory effect on the growth of Plasmodium falciparum in vitro. To further investigate the role of retinoids as potential antimalarial agents, we assessed the effect of all-trans-retinoic acid (RA), 9-cis-RA and 13-cis-RA, as well as retinol itself and its ester, retinyl palmitate, on 3H-hypoxanthine uptake by the laboratory-adapted strains of P. falciparum 3D7 and K1. In addition, we examined the influence of three specific RA receptor antagonists, ER 27191, Ro 415253 and AGN 194301, on retinoid-induced growth inhibition of 3D7. All-trans-RA, 9-cis-RA and 13-cis-RA in concentrations ranging from 1 x 10(-4) to 5 x 10(-10) M each had antimalarial activity, but at IC50 values (5.9 x 10(-5) to 7.9 x 10(-5) M) that were less than those of retinol (2.5 x 10(-5) to 3.2 x 10(-5) M). Retinyl palmitate had minimal effect on 3H-hypoxanthine uptake. Each of the three specific antagonists inhibited growth of 3D7 (IC50 range 1.2 x 10(-5) to 3.0 x 10(-5) M) but, in isobolographic analysis, were antagonistic to retinol (dose factor potentiation, DFP 0.46-0.79) and, in the case of Ro 415253, to all-trans-RA (DFP=0.39). Although we did not attempt to quantify losses of retinoids from the system, these data suggest that retinol has greater antimalarial activity than its RA metabolites and especially retinyl palmitate. The specific RA receptor antagonists showed paradoxical antimalarial activity but consistently antagonised the effect of retinol and all-trans-RA in isobolographic experiments. We conclude that RA metabolites may be less suitable than retinol per se as antimalarial agents and that P. falciparum might possess or acquire a RA receptor-like moiety.

The specific inhibition of 11-cis-retinyl palmitate formation in the frog eye by diaminophenoxypentane, an inhibitor of rhodopsin regeneration.

The antischistosomal drug 1,5-di-(p-aminophenoxy) pentane (DAPP), an inhibitor of rhodopsin regeneration in the vertebrate retina, is shown to completely block the production of 11-cis-retinyl palmitate in the frog eye. An untreated frog generates a large amount of 11-cis-retinyl palmitate during 1-2 days in the dark after a strong bleach. Also, it is demonstrated that DAPP can deplete the stores of 11-cis-retinyl palmitate in the dark-adapted frog eye. The specificity of DAPP's inhibition of dark-adaptation is explored, and the usefulness of employing retinotoxic drugs to investigate the physiology and biochemistry of rhodopsin regeneration is discussed.

Cornification of esophagus induced by excessive vitamin E.

The antagonistic effects of vitamin E on vitamin A were studied in chickens fed excessive amounts of vitamin E (700-7000 IU/kg diet) for 6 wk. Serum levels of vitamin A and vitamin E were determined by high-performance liquid chromatography at 2, 4, and 6 wk after vitamin E supplementation. Vitamin E in serum reached maximum levels 4 wk after supplementation. Vitamin E tended to ameliorate the normalization of serum levels of vitamin A. To examine the pathological lesions induced by excessive vitamin E in chickens, two to four chickens were necropsied every 2 wk after supplementation. The results in gross and microscopic lesions showed that cornification of esophageal mucous membrane was found in chickens supplemented with > or = 1400 IU/kg of vitamin E in diet for 6 wk. Lesions of this kind resemble those in vitamin A-deficient chickens and are the first to be induced by excess vitamin E.

Blockade of the initiation of murine odontogenesis in vitro by citral, an inhibitor of endogenous retinoic acid synthesis.

Endogenous retinoids are present in the embryonic mouse mandible and reach a concentration peak immediately before the formation of the dental lamina. Because exogenous retinoids alter the pattern of the dental lamina and the expression of epidermal growth factor mRNA (a transcript necessary for initiation of odontogenesis), the role of retinoic acid in the initiation of odontogenesis was studied here. Citral (3,7-dimethyl-2,6-octadienal), a known inhibitor of retinoic acid synthesis, was used to block the endogenous synthesis of retinoic acid in the mouse embryonic mandible before the formation of the dental lamina (gestational day 9). A 24-h exposure to citral totally blocked tooth formation in 7/10 mandibles. Reductions of endogenous retinoic acid concentrations were confirmed by high-performance liquid chromatography. Tooth formation was restored by simultaneous treatment with all-trans retinoic acid or 9-cis retinoic acid during the citral exposures (first 24 h of culture). Endogenous retinoic acid is necessary for the initiation of odontogenesis.

Developmental toxicity evaluation of inhaled citral in Sprague-Dawley rats.

Citral is a commonly used fragrance and flavour ingredient that has demonstrated a potential for teratogenicity in chick embryo screening studies. To investigate potential mammalian developmental toxicity, pregnant Sprague-Dawley rats were exposed to citral by inhalation for 6 hr/day on gestation days 6-15 at mean concentrations of 0, 10 or 34 ppm as vapour, or 68 ppm as an aerosol/vapour mixture. Dams were killed on gestation day 20 and the foetuses were removed and evaluated for gross, visceral and skeletal malformations. Exposure to 68 ppm was maternally toxic, with reduced body-weight gains, ocular opacity, breathing difficulty, nasal discharge and salivation noted in the dams. No maternal toxicity was seen at the lower vapour exposure levels. The number of corpora lutea, implantations, resorptions, foetal viability, litter size, and sex ratio were not adversely affected by citral at any exposure level tested, and no exposure-related malformations were observed. At a maternally toxic exposure level, a slight reduction in mean foetal body weight and a slight increase in the incidence of hypoplastic bones were noted. Results of this study indicate that citral does not produce developmental toxicity in the rat when administered by inhalation at concentrations up to a maternally toxic exposure level.

Comparison of the toxicity of citral in F344 rats and B6C3F1 mice when administrated by microencapsulation in feed or by corn-oil gavage.

A study of the potential effects of microencapsulation on the toxicity of citral was conducted in 14-day continuous feeding studies with both sexes of F344 rats and B6C3F1 mice. Toxicity by the feeding route was compared with that from bolus doses of the neat chemical in corn oil administrated by gavage. Both sexes of rats and mice were given diet containing 0, 0.63, 1.25, 2.5, 5 and 10% citral microcapsules. These feed formulations were equivalent to daily doses of 0, 142, 285, 570, 1140 and 2280 mg citral/kg body weight for rats and 0, 534, 1068, 2137, 4275 and 8550 mg citral/kg body weight for mice. The daily gavage doses were 0, 570, 1140 and 2280 mg citral/kg body weight for both sexes of rats, and 0, 534, 1068 and 2137 mg citral/kg body weight for both sexes of mice. Citral microcapsules administered in the diet did not cause mortality in mice or rats. Toxicity was confined to decreases in body weight at the 10% concentration in mice, at the 5 and 10% concentrations in rats, and decreases in absolute weights of the liver, kidney and spleen at the 10% concentration in rats. The only histopathological change observed was minimal to mild hyperplasia and/or squamous metaplasia of the respiratory epithelium in the anterior portion of the nasal passages of rats fed 5 or 10% citral microcapsules. By contrast, citral gavage caused mortality in five out of five male and female mice at 2137 mg/kg body weight, and in two out of five male mice at 1068 mg/kg body weight. There were dose-related increases in absolute liver weights of male and female mice. Cytoplasmic vacuolization of hepatocytes occurred in all female mice gavaged with 1068 and 2137 mg citral/kg body weight, and in male mice from the 2137 mg/kg dose group. Necrosis, ulceration and/or acute inflammation of the forestomach occurred in the high-dose mice of both sexes. Inflammation and/or hyperplasia of the forestomach occurred in about half of the male and female mice dosed with 1068 mg citral/kg. Citral gavage at doses that were equivalent to up to 10% in the diet (2280 mg/kg body weight) did not cause toxicity in rats, except for minimal hyperplasia of the squamous epithelium of the forestomach in high-dose males.(ABSTRACT TRUNCATED AT 400 WORDS)

Impairment of vitamin A uptake by rat hepatocytes and fat storing cells determined by Monensin--morphological observations.

The action of the Na+/H+ antiport monensin on vitamin A uptake by rat liver has been studied in vivo. The quickfading autofluorescence of vitamin A has been used for the determination of vitamin A uptake by the liver. Pretreatment of rats intraperitoneally with monensin decreases the uptake of vitamin A by hepatocytes and its transfer for storage to fat storing cells. Pretreatment of rats intraperitoneally with vitamin A for a short time, then with monensin, shows that the hepatocytes no longer transfer vitamin A to fat storing cells for storage. These results might indicate that monensin impairs the uptake of vitamin A by the hepatocytes and might also impair the transport of vitamin A from parenchymal to perisinusoidal cells.

Hepatic mitochondrial membranolysis repairing by spermidine.

Hepatic mitochondrial membrane lysis is caused due to excess vitamin A, has been repaired by spermidine. This fact has been proved by estimating membrane proteins, lipids, phospholipase A2 activity and membrane phospholipids of rat liver mitochondria by studying the effect of spermidine on membranolytic effect of excess vitamin A. Spermidine has been found to inhibit the activity of phospholipase A2 and thus stabilize the hepatic mitochondrial membranes in the hypervitaminoic A model, that is to say, the spermidine tries to bring down the enormously elevated levels of phospholipase A2 by administration of excess vitamin A in rats.

[Campaign against allergenic moulds in dwellings. Inhibitor properties of essential oil of Geranium 'Bourbon', citronellol, geraniol and citral]. / Lutte contre les moisissures allergisantes des habitations. Propriétés inhibitrices de l'huile essentielle de Géranium 'Bourbon', du citronellol, du géraniol et du citral.

Many fungal airborne spora show allergenic effects. Indoor (dwelling, work rooms, hospital chambers) can be disinfected by elimination of living particles. We have undertaken experiments in more and more spacious bulks for evaluation of the antifungal effects of vapours of essential oils and some volatiles compounds. Results show that the Mucorales and Geotrichum resist strongly. On the contrary, the Cladosporium strains, some Aspergillus and Penicillium, Trichothecium roseum are the most sensitive, specially towards the citral vapours. Experiments in hospital can be undertaken.

[Retinol level, superoxide dismutase activity and the degree of lipid peroxidation in rats with drug-induced collagenosis]. / Poziom retinolu i aktywnosc dysmutazy ponadtlenkowej a nasilenie peroksydacji lipidów u szczurów w przebiegu polekowej kolagenozy.

The retinol effect on symptoms of late toxicity of hydralazine in rats of Wistar strain during induction of the collagenosis-like syndrome has been studied. Studies have been performed during 360 days, and examination were done in three months lasting intervals. Animals were divided into 3 groups: the first was treated with hydralazine, the second with hydralazine plus retinol, and the third corresponded to the control group. It has been stated that the long-term administration of hydralazine caused the lowering of the retinol level in the serum and liver progressing according to the time of the drug use. The mean lowering of the retinol concentration for animals of the first group was 20.7% in the serum and 24.7% in the liver. Analogous results in the second group were 12.1% and 14.7%, respectively. Simultaneously activity of superoxide dismutase measured in the kidney and heart muscle homogenates was significantly lowered in animals receiving hydralazine solely. Retinol administered together with hydralazine caused an increase in the enzyme activity (about 30%) when compare with animals treated only with hydralazine. The lowering of the retinol level and of dismutase activity caused beneficial conditions for increased lipid peroxidation measured by an increase in the malonic aldehyde concentration. The concentration of malonic dialdehyde in kidneys of rats treated solely with hydralazine increased about twofold, and in the heart muscle about 3.5-fold. The supplementation of the diet with retinol in rats treated solely with hydralazine partially limited effects of enhanced free radical activity reflected in increased lipid peroxidation.