RESUMO
The objective of this study was screening of ommochromes from the compound eyes of insects and comparison of their antioxidant properties. Ommochromes were isolated in preparative quantities from insects of five different families: Stratiomyidae, Sphingidae, Blaberidae, Acrididae, and Tenebrionidae. The yield of ommochromes (dry pigment weight) was 0.9-5.4% of tissue wet weight depending on the insect species. Isolated pigments were analyzed by high-performance liquid chromatography and represented a mixture of several ommochromes of the ommatin series. The isolated ommochromes displayed a pronounced fluorescence with the emission maxima at 435-450 nm and 520-535 nm; furthermore, the emission intensity increased significantly upon ommochrome oxidation with hydrogen peroxide. The ommochromes produced a stable EPR signal consisting of a singlet line with g = 2.0045-2.0048, width of 1.20-1.27 mT, and high concentration of paramagnetic centers (> 1017 spin/g dry weight). All the investigated ommochromes demonstrated high antiradical activity measured from the degree of chemiluminescence quenching in a model system containing luminol, hemoglobin, and hydrogen peroxide. The ommochromes strongly inhibited peroxidation of the photoreceptor cell outer segments induced by visible light in the presence of lipofuscin granules from the human retinal pigment epithelium, as well as suppressed iron/ascorbate-mediated lipid peroxidation. The obtained results are important for understanding the biological functions of ommochromes in invertebrates and identifying invertebrate species that could be used as efficient sources of ommochromes for pharmacological preparations to prevent and treat pathologies associated with the oxidative stress development.
Assuntos
Antioxidantes/farmacologia , Fenômenos Químicos , Olho Composto de Artrópodes/química , Insetos/metabolismo , Fenotiazinas/farmacologia , Epitélio Pigmentado da Retina/metabolismo , Animais , Olho Composto de Artrópodes/metabolismo , Peróxido de Hidrogênio , Insetos/efeitos dos fármacos , Luz , Peroxidação de Lipídeos , Oxirredução , Epitélio Pigmentado da Retina/efeitos dos fármacosRESUMO
The effect of superoxide radicals on melanin destruction and degradation of melanosomes isolated from cells of retinal pigment epithelium (RPE) of the human eye was studied. We found that potassium superoxide causes destruction of melanin in melanosomes of human and bovine RPE, as well as destruction of melanin from the ink bag of squid, with the formation of fluorescent decay products having an emission maximum at 520-525 nm. The initial kinetics of the accumulation of the fluorescent decay products is linear. Superoxide radicals lead simultaneously to a decrease in the number of melanosomes and to a decrease in concentration of paramagnetic centers in them. Complete degradation of melanosomes leads to the formation of a transparent solution containing dissolved proteins and melanin degradation products that do not exhibit paramagnetic properties. To completely degrade one melanosome of human RPE, 650 ± 100 fmol of superoxide are sufficient. The concentration of paramagnetic centers in a melanolipofuscin granule of human RPE is on average 32.5 ± 10.4% (p < 0.05, 150 eyes) lower than in a melanosome, which indicates melanin undergoing a destruction process in these granules. RPE cells also contain intermediate granules that have an EPR signal with a lower intensity than that of melanolipofuscin granules, but higher than that of lipofuscin granules. This signal is due to the presence of residual melanin in these granules. Irradiation of a mixture of melanosomes with lipofuscin granules with blue light (450 nm), in contrast to irradiation of only melanosomes, results in the appearance of fluorescent melanin degradation products. We suggest that one of the main mechanisms of age-related decrease in melanin concentration in human RPE cells is its destruction in melanolipofuscin granules under the action of superoxide radicals formed during photoinduced oxygen reduction by lipofuscin fluorophores.
Assuntos
Melaninas/metabolismo , Melanossomas/metabolismo , Animais , Bovinos , Decapodiformes/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Humanos , Cinética , Luz , Lipofuscina/química , Lipofuscina/metabolismo , Melaninas/química , Melanossomas/efeitos dos fármacos , Melanossomas/efeitos da radiação , Oxirredução/efeitos dos fármacos , Oxirredução/efeitos da radiação , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Superóxidos/química , Superóxidos/metabolismo , Superóxidos/farmacologiaRESUMO
We studied the capacity of DOPA-melanin (natural eumelanin analog) to bind chromophore A2E of retinal pigmented epithelial cell lipofuscin granule into complexes. DOPA-melanin bound up to 200 nm A2E per 1 mg polymer; antioxidant activity of the resultant complexes was evaluated. Luminol chemiluminescence quenching in the presence of hydrogen peroxide showed that the chemiluminescence latency/concentration constants were virtually the same for DOPA-melanin and its A2E complexes. Comparison of the inhibitory effects of DOPA-melanin and DOPA-A2E complexes by rate of UV-induced peroxidation of the outer segments of photoreceptor cells showed higher inhibitory activity of the complexes in comparison with pure DOPA-melanin. Antioxidant activity of DOPA-A2E complexes towards Fe(2+)-ascorbate-induced peroxidation of the outer segments of photoreceptor cells was also higher than that of DOPA-melanin. The results indicated that chromophore A2E of lipofuscin granules in the studied concentrations did not attenuate the antioxidant effects of DOPA-melanin and even potentiated it. This suggested that A2E excess in retinal pigmented epithelium cells could be bound by melanosome melanin and lose its toxicity.
Assuntos
Antioxidantes/metabolismo , Di-Hidroxifenilalanina/análogos & derivados , Epitélio Pigmentado Ocular/metabolismo , Compostos de Piridínio/metabolismo , Retinoides/metabolismo , Animais , Antioxidantes/química , Bovinos , Células Cultivadas , Di-Hidroxifenilalanina/química , Di-Hidroxifenilalanina/metabolismo , Células Epiteliais/química , Células Epiteliais/metabolismo , Lipofuscina/química , Melaninas/metabolismo , Melanossomas/metabolismo , Oxirredução , Retina/citologiaRESUMO
Photoprotective activity of heteroaromatic compounds (derivatives of 3-hydroxypyridine, amino-6-hydroxybenzothiazole, and 5-hydroxybenzimidazole) was studied in the system of UV-induced cardiolipin peroxidation. Although all three compounds had the antioxidant effect during free radical oxidation of luminol, only derivatives of amino-6-hydroxybenzothiazole and 5-hydroxybenzimidazole inhibited the process of UV-induced lipid peroxidation. The 3-hydroxypyridine derivative did not inhibit UV-induced cardiolipin peroxidation, which was probably related to degradation of this compound under the influence of UV light and formation of degradation products that cannot inhibit free radical processes.
Assuntos
Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Antioxidantes/química , Benzimidazóis/química , Cardiolipinas/química , Radicais Livres/química , Estrutura Molecular , Oxirredução/efeitos dos fármacos , Oxirredução/efeitos da radiação , Piridinas/química , Tiazóis/química , Raios UltravioletaRESUMO
The high-grade fluorinated silicone oil made in Russia was tested for its effect on the rabbit retinal antioxidant status. Experiments were made on 36 rabbits (72 eyes) undergoing replacement of the excised vitreous body with sterile 0.9 NaCl solution or with one of the study implants (fluorinated silicon oil, silicon oil, or perfluorodecahydronaphthalene) after subtotal vitrectomy. The impact of the study implants on the rabbit retinal antioxidant status was postoperattively investigated. The experimental findings suggest that the high-grade fluorinated silicon oil made in Russia may be used as an implant for short-term vitreous chamber tamponade.
Assuntos
Antioxidantes , Retina/efeitos dos fármacos , Óleos de Silicone/farmacologia , Vitrectomia , Experimentação Animal , Animais , Implantes de Medicamento , Coelhos , Óleos de Silicone/administração & dosagem , Fatores de TempoRESUMO
The inhibiting effect of melanin synthesized from dihydroxyphenylalanine (DOPA), dopamine, adrenaline and adrenolutin on the ultraviolet- or the Fe(2+)-ascorbic acid-induced peroxidation of cardiolipin liposomes has been studied. All these melanins are able to inhibit both the ultraviolet- and the Fe(2+)-ascorbic acid-induced lipid peroxidation. Antioxidative activity of melanins enhances in the order: dopamine-melanin less than melanin synthesized from dopamine in the presence of Cu(2+) less than DOPA--melanin less than melanin synthesized from adrenaline in the presence of Cu(2+) approximately equal to adrenolutin-melanin, and correlates with their ability to scavenge superoxide anion radical. The optical screening effect of the investigated melanins in the inhibition of lipid peroxidation was not higher than 15% for the most active melanins.
Assuntos
Antioxidantes/farmacologia , Cardiolipinas/química , Di-Hidroxifenilalanina/análogos & derivados , Lipossomos/química , Melaninas/farmacologia , Ácido Ascórbico , Cardiolipinas/efeitos da radiação , Di-Hidroxifenilalanina/síntese química , Di-Hidroxifenilalanina/farmacologia , Dopamina/análogos & derivados , Dopamina/farmacologia , Epinefrina/análogos & derivados , Epinefrina/farmacologia , Compostos Ferrosos , Indóis/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Melaninas/síntese química , Nitroazul de Tetrazólio/química , Fotoquímica , Raios UltravioletaRESUMO
The naturally occurring compound N alpha-acetylcarnosine (NAC) is proposed as the prodrug of L-carnosine (C) resistant to enzymatic hydrolysis by human serum carnosinase. Rabbit eyes were treated with 1% NAC, C or placebo and extracts of the aqueous humor from the anterior eye chamber were analyzed for imidazole content by reverse phase analytical high performance liquid chromatography (HPLC), thin-layer (TLC) and ion-exchange chromatographic techniques. The topical administration of pure C to the rabbit eye did not lead to accumulation of this compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eye. NAC showed dose-dependent hydrolysis in its passage from the cornea to the aqueous humor, releasing C after 15. 30 min of ocular administration of prodrug in a series of therapeutical modalities: instillation < or = subconjunctival injection < or = ultrasound induced phoresis. Different treatment techniques showed excellent toleration of 1% NAC by the eye. Once in the aqueous humor, C might act as an antioxidant and enter the lens tissue when present at effective concentrations (5-15 mmol/l). The advantage of the ophthalmic prodrug NAC and its bioactivated principle C as universal antioxidants relates to their ability to give efficient protection against oxidative stress both in the lipid phase of biological membranes and in an aqueous environment. NAC is proposed to treat ocular disorders which have the component of oxidative stress in their genesis (cataracts, glaucoma, retinal degeneration, corneal disorders, ocular inflammation, complications of diabetes mellitus, systemic diseases).
Assuntos
Antioxidantes/farmacocinética , Carnosina/análogos & derivados , Carnosina/farmacocinética , Soluções Oftálmicas , Animais , Carnosina/administração & dosagem , Cromatografia Líquida de Alta Pressão , Humanos , Cápsula do Cristalino/efeitos dos fármacos , Cápsula do Cristalino/metabolismo , Peróxidos Lipídicos/metabolismo , Masculino , Estresse Oxidativo , Coelhos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The action of ocular screening pigments of vertebrates (melanins) as well as those of invertebrates (ommochromes) on lipid peroxidation has been studied. Lipid peroxidation has been induced by one of the following systems: Fe2+ + ascorbic acid; Fe2+ + NADPH + liver microsomes; xanthine + xanthine oxidase; u.v. illumination; intense visible light, high concentration of O2. Measurements of the lipid peroxidation rate, as estimated from the accumulation of malonic dialdehyde, showed a sharp decrease of the lipid peroxidation rate in the presence of either melanosomes or ommochromes. Synthetic DOPA melanin was also found to exert a strong inhibiting effect on lipid peroxidation. A comparative study of lipid peroxidation in retinal pigment epithelium (RPE) of pigmented and albino rabbits demonstrated that the latter tissue is more sensitive to the effect of the above mentioned prooxidant systems. Apparently this finding is related to the presence of melanin-containing granules in the pigmented tissue rather than to differences in efficiency of other endogenous antioxidant systems. The activities of superoxide dismutase and glutathione peroxidase are practically equal in the RPE of pigmented and albino rabbits whereas the alpha-tocopherol content is higher in albinos. Possible mechanisms of inhibition of lipid peroxidation by melanosomes and ommochromes are discussed. It is proposed that their antioxidant function is one of the most important physiological features of melanins (vertebrate eye) and ommochromes (invertebrate eye).
Assuntos
Antioxidantes , Peróxidos Lipídicos/metabolismo , Melaninas/fisiologia , Fenotiazinas/farmacologia , Albinismo/metabolismo , Animais , Decápodes , Fenotiazinas/fisiologia , Epitélio Pigmentado Ocular/metabolismo , Coelhos , Rana temporaria , Retina/metabolismoRESUMO
Electron spin resonance (ESR) examinations of human retinal pigment epithelium melanosomes isolated from eyes of young and old donors were carried out. The examined ESR signal was a single line, which is characteristic for free radicals of eumelanin o-semiquinones. The content of free radicals related to melanosomes dry weight for samples from older donors (ages over 45 years) were higher than for sample from younger donors (between 14 and 22 years). Simultaneously, the content of free radicals calculated for one melanosome is constant and does not depend on age. The homogeneous broadening of the recorded ESR lines shows that there are no isolated spin packets in all investigated melanin samples. Slow spin-lattice (T1 approximately 10(-5) s) and fast spin-spin (T2 approximately 10(-8) s) relaxation processes occur in these samples. Saturation of the ESR lines at low microwave power was measured. High concentration of free radicals in melanosome samples was responsible for the fast spin-spin relaxation process.
Assuntos
Melanossomas/ultraestrutura , Epitélio Pigmentado Ocular/crescimento & desenvolvimento , Epitélio Pigmentado Ocular/ultraestrutura , Adolescente , Adulto , Fatores Etários , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Radicais Livres/análise , Humanos , Pessoa de Meia-IdadeRESUMO
The influence of lipofuscin granules and melanosomes from human retinal pigment epithelium on the light-induced photooxidation of cardiolipin liposomes and the generation of superoxide radicals was studied. Lipofuscin granules were able to stimulate, while melanosomes inhibited, the cardiolipin photooxidation. The visible light irradiation of both melanosomes and lipofuscin granules generated superoxide radicals with mean rates of 1.5 nmole/min/10(7) and 38 nmole/min/10(7) granules, accordingly. However, melanosomes but not lipofuscin granules reacted readily with superoxide radicals. Moreover, the rate constant of degradation of superoxide radicals in the presence of melanosomes was about five orders of magnitude higher than the rate constant of its photogeneration. Therefore, we propose that melanosomes in retinal pigment epithelium cells have a photoprotective role whereas lipofuscin granules may stimulate photodestructive reactions.
Assuntos
Cardiolipinas/efeitos da radiação , Grânulos Citoplasmáticos/fisiologia , Lipofuscina/fisiologia , Melanossomas/fisiologia , Epitélio Pigmentado Ocular/citologia , Adulto , Idoso , Cardiolipinas/metabolismo , Humanos , Cinética , Lipossomos , Pessoa de Meia-Idade , Oxirredução , FotoquímicaRESUMO
Effect of three inhibitors of free radical processes (IFRP) differing in antiradical activity (2-tret. butyl-6-methyl-3-oxipyridin, 2-ethyl-6-methyl-3-oxipyridin and 3-oxipyridin) on paramagnetic centres of melanoprotein granules of pigment epithelium was studied by ESR method at room temperature. It was shown that IFRP decreased the dark signal and that the reaction of paramagnetic particles dissociation proceeded according to the equation of the first order reaction. The rate constants of these reactions were calculated. It was found that the relative amount of reacting and non-reacting paramagnetic particles with the inhibitor depended on the nature and concentration of IFRP.
Assuntos
Proteínas do Olho , Melaninas , Epitélio Pigmentado Ocular/ultraestrutura , Animais , Anuros , Fenômenos Químicos , Química , Grânulos Citoplasmáticos , Escuridão , Espectroscopia de Ressonância de Spin Eletrônica , Radicais Livres , Técnicas In Vitro , PiridinasRESUMO
The intensity of peroxide oxidation of lipids in the pigmented epithelium of the eye, under hyperoxic conditions, is approximately 6 times lower in pigmented rabbits as compared to albino ones. In pigmented animals, the pigmented epithelium of the eye exerts evident protective effect during the action of oxygen on the retina. It is suggested that the observed inhibition of peroxide oxidation of lipids in the pigmented epithelium of pigmented animals is due to anti-oxidative effect of melanoprotein granules.
Assuntos
Melaninas/metabolismo , Consumo de Oxigênio , Epitélio Pigmentado Ocular/metabolismo , Proteínas/metabolismo , Animais , Cinética , Peróxidos Lipídicos/metabolismo , Oxirredução , Coelhos , Retina/metabolismoRESUMO
Melanosomes from retinal pigmented epithelium readily inhibit photooxidation of lipids. This effect is due to both passive screening of light and chemical interaction of melanosomes with products of oxidation. The role of melanosomes is discussed in the system of optic and chemical protection of eye structures from photo injury. It is suggested that in other tissues (skin) melanosomes account for the similar function of optic and chemical (antioxidative) protection from the injurious effect of UV and visible light.
Assuntos
Traumatismos Oculares/prevenção & controle , Luz/efeitos adversos , Melanócitos/efeitos da radiação , Pigmentos Biológicos/efeitos da radiação , Animais , Cardiolipinas/metabolismo , Cardiolipinas/efeitos da radiação , Interações Medicamentosas , Traumatismos Oculares/etiologia , Traumatismos Oculares/metabolismo , Cobaias , Metabolismo dos Lipídeos , Lipídeos/efeitos da radiação , Lipossomos/metabolismo , Lipossomos/efeitos da radiação , Melanócitos/metabolismo , Oxirredução/efeitos da radiação , Epitélio Pigmentado Ocular/metabolismo , Epitélio Pigmentado Ocular/efeitos da radiação , Pigmentos Biológicos/metabolismo , Raios Ultravioleta/efeitos adversosRESUMO
The ability of melanosomes from human, bovine and frog retinal pigment epithelium cells (RPE) to bind A2E fluorophore of RPE lipofuscin granules and products of A2E photooxidation is investigated. RPE melanosomes are found to bind A2E molecules themselves as well as the molecules formed after A2E irradiation by visible light. In our experiments single melanosome was able to bind up to 0.08 fmol A2E. Antioxidant activity of melanosomes is compared to antioxidant activity of their complexes with A2E. It is shown by luminal chemiluminescence quenching in the presence of hydrogen peroxide that in A2E/melanosomes complex the chemiluminescence quenching is not significantly reduced. Comparison of inhibitory activity of melanosomes and their complexes with A2E on UV-induced (light conditions) and Fe(2+)-ascorbate-induced (dark conditions) peroxidation of photoreceptor outer segments (POS) demonstrated that bound A2E does not affect inhibitory ability of melanosomes in both systems. Thus, binding of A2E to RPE melanosomes in concentrations from 0.01 to 0.1 fmol A2E per melanosome does not significantly alter their antioxidant properties. It is supposed that both A2E and hydrophilic products of its photooxidation could be bound by RPE melanosomes and, thus, it lost the ability to exhibit toxic properties.
Assuntos
Antioxidantes/metabolismo , Células Epiteliais/química , Melanossomas/metabolismo , Compostos de Piridínio/metabolismo , Epitélio Pigmentado da Retina/química , Retinoides/metabolismo , Animais , Antioxidantes/química , Ácido Ascórbico/química , Bovinos , Fracionamento Celular , Humanos , Peróxido de Hidrogênio/química , Lipofuscina/química , Medições Luminescentes , Melanossomas/química , Oxirredução , Processos Fotoquímicos , Compostos de Piridínio/antagonistas & inibidores , Compostos de Piridínio/síntese química , Rana ridibunda , Retinoides/antagonistas & inibidores , Retinoides/síntese química , Raios UltravioletaRESUMO
An original representative of histamine-containing peptidomimetics L-glutamyl-histamine (L-Glu-Hist) was synthesized and characterized as a cytokine mimic leading to cellular responses of improved specificity. The energy-minimized 3-D conformations of L-Glu-Hist derived from its chemical structure resulted in stabilization for Fe(2+) chelating complexes. L-Glu-Hist accelerated the decrease of ferrous iron in the ferrous sulphate solution in a concentration-dependent mode and showed the ferroxidase-like activity at concentrations less than 3 mm in the phenanthroline assay, whereas in the concentration range 3-20 mm L-Glu-Hist restricted the availability of Fe(2+) to phenanthroline due to binding of ferrous ions in chelating complexes. L-Glu-Hist showed a stimulatory effect on phosphatidylcholine liposomal peroxidation (LPO) catalysed by the superoxide anion radical (O(2) (*))-generating system (Fe(2+)+ ascorbate) at low (less or about 1 mm) L-Glu-Hist concentrations and both revealed the inhibitory effect on LPO in this system of high ( approximately 10 mm) L-Glu-Hist concentration. L-Glu-Hist released O(2) (*) in concentrations which stimulated [(3)H]-thymidine incorporation into DNA and proliferation of mouse spleen lymphocytes and mononuclear cells from human blood. The structural peptide-like analogues of L-Glu-Hist such as L-Glu-Trp, carcinine (beta-alanylhistamine), but not L-Pro-Glu-Trp were active in stimulating thymidine incorporation and in inducing proliferation of mononuclear cells compared to mitogen concanavalin A at doses 2.5-25.0 microg/ml. Our data provide evidence that L-Glu-Hist may act as a very fast and sensitive trigger for lymphocyte proliferation and immunoregulation.
Assuntos
Linfócitos/efeitos dos fármacos , Oligopeptídeos/farmacologia , Animais , Técnicas de Cultura de Células , Proliferação de Células/efeitos dos fármacos , Concanavalina A/farmacologia , Relação Dose-Resposta a Droga , Radicais Livres/metabolismo , Humanos , Quelantes de Ferro/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mitógenos/farmacologia , Oligopeptídeos/síntese química , Oligopeptídeos/química , Oxirredução , Conformação ProteicaRESUMO
Removal of melanosomes from retinal pigment epithelium cells is accompanied by a sharp rise in the rate of VIS light-induced lipid peroxidation. The synthetic DOPA-melanin effectively suppresses the UV light-induced lipid peroxidation of cardiolipin not only through a passive decrease of irradiation (optical screening), but also by active chemical inhibition of the reaction. It is assumed that the observed active inhibition is due to the interaction between DOPA-melanin and the free radical products generated in cardiolipin upon UV illumination. It is concluded that the high photoresistance of melanin-containing cells of retinal pigment epithelium is due to the ability of melanosomes to exert strong inhibition of photo-induced lipid peroxidation.
Assuntos
Di-Hidroxifenilalanina/análogos & derivados , Metabolismo dos Lipídeos , Epitélio Pigmentado Ocular/metabolismo , Animais , Depressão Química , Di-Hidroxifenilalanina/farmacologia , Técnicas In Vitro , Melanócitos/metabolismo , Oxirredução , Fotoquímica , Rana temporariaRESUMO
The efficiency of lipid peroxidation inhibition by retinal pigment epithelium of pigmented rabbits is higher than that of albino rabbits. The superoxide dismutase and glutathione peroxidase activities are nearly the same in both tissues; the alpha-tocopherol content is higher in retinal pigment epithelium of albino animals; the oxidation of the pigment epithelium lipid fraction si higher in pigmented animals. It is concluded that the high resistance of pigmented tissue to the effects of prooxidant systems is due to the presence of melanoprotein granules in the pigment epithelium.
Assuntos
Albinismo/metabolismo , Peróxidos Lipídicos/metabolismo , Epitélio Pigmentado Ocular/metabolismo , Animais , Encéfalo/metabolismo , Glutationa Peroxidase/metabolismo , Cinética , Oxirredução , Epitélio Pigmentado Ocular/enzimologia , Coelhos , Superóxido Dismutase/metabolismo , Vitamina E/metabolismoRESUMO
Comparative electron microscopic, electrophysiological and biochemical studies of thioridazine influence on lipid peroxidation in vivo (rats, rabbits) and in vitro (model systems) were performed. It was shown that thioridazine retinopathy was not followed by an increase in lipid peroxidation and antioxidant (dibunol) failed to protect the retina against the destructive action of thioridazine. Moreover, thioridazine inhibited lipid peroxidation in model system.