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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the inhibitory effect of melatonin, a recently discovered scavenger of free radicals, on cataract formation in the newborn rat. The glutathione synthesis inhibitor, buthionine sulfoximine (BSO) (3 mmol/kg), was intraperitoneally injected into newborn rats for 3 consecutive days starting on day 2 after birth. These glutathione depleted rats develop cataracts. Melatonin (4 mg/kg) was injected intraperitoneally into half of the rats once a day beginning at day 2 after birth; the other half of the animals received solvent daily. The incidence of cataract was observed on day 16, after the eyes of the newborn animals had opened. Both reduced glutathione (GSH) and oxidized glutathione (GSSG) levels were measured. Cataracts were observed in all animals (18/18) treated with BSO plus solvent. The incidence of the cataract in the animals cotreated with melatonin was only 6.2% (1/15). Total lenticular glutathione (GSH + GSSG) levels in BSO only treated rats were reduced by 97%. The total glutathione in the lens of the BSO plus melatonin group was significantly higher (by 3%) than that of the BSO only group. The percentage of the total glutathione as GSSG for the BSO plus solvent group was higher than the control value. Cotreatment of BSO injected rats with melatonin (4 mg/kg/day) clearly reduced cataract formation proving that it is directly or indirectly protective against oxidative stress which accompanies glutathione deficiency. The inhibitory effects of melatonin on cataract formation in this study could be due to melatonin's free radical scavenging activity or due to its stimulatory effect on glutathione production.
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PMID:Inhibitory effect of melatonin on cataract formation in newborn rats: evidence for an antioxidative role for melatonin. 786 32

The pineal hormone melatonin exhibits remarkable functional versatility. Shortly after its discovery, melatonin was functionally linked to the regulation of the neuroendocrine axis, particularly to the reproductive system. However, judging from the wide variety of cellular changes that occurred following either pinealectomy, to remove the primary source of melatonin, or the exogenous administration of the indole, it was obvious that the activity of melatonin far transcended its actions on the hypothalamo-pituitary-gonadal system. Roughly 30 months ago it was discovered that melatonin is a highly efficient free radical scavenger and general antioxidant. This implied that melatonin, which is both lipophilic and hydrophilic, has effects not only in every cell but also within every subcellular compartment. These intracellular actions of melatonin, some of which are independent of any receptor interaction and some of which are mediated by nuclear receptors, have become the focus of much of the current investigation. As an antioxidant, melatonin has been shown in vitro to be a highly efficient scavenger of the very reactive and toxic hydroxyl radical. Indeed, on an equimolar basis melatonin proved significantly more efficient in neutralizing the hydroxyl radical than did the two well-known scavengers, glutathione and mannitol. Likewise, melatonin was found to also scavenge the peroxyl radical which is generated during lipid peroxidation; in this regard it was roughly twice as effective as vitamin E (alpha-tocopherol). The antioxidant activities of melatonin have been well documented in tissue homogenates and organisms as well. When rats are treated with the chemical carcinogen safrole, this agent induces the generation of free radicals which in turn extensively damage nuclear DNA; this damage is almost totally eliminated if the animals are cotreated with melatonin. Also, damage to DNA in human lymphocytes due to ionizing radiation, another treatment which is known to induce free radical formation, is greatly reduced if the cells are treated with melatonin prior to radiation. Cytosolic protein seems also to be protected from free radical damage when melatonin is present. When newborn rats are treated with a glutathione-depleting drug at birth, by 2 weeks of age the animals have cataracts. Cataracts form because oxidants damage protein in the presence of low intracellular levels of glutathione. Cataracts induced by this means are essentially prevented if the glutathione-depleted rats are supplemented with melatonin. Finally, membrane lipid peroxidation, induced either in vivo or in vitro by any of several means, all of which involve free radicals, is drastically attenuated in the presence of melatonin. Considering melatonin's ability to cross all morphophysiological barriers and to enter every cell, and all subcellular compartments, the implication is that this indole may play a very important role in the antioxidative defense system of the organism. These findings potentially have important implications for a wide variety of age-related diseases and to aging itself. Melatonin's control of reproductive physiology in photoperiodic mammals is well documented. However, the site of interaction of melatonin with the neuroendocrine axis has been especially difficult to determine. The discovery and cloning of a membrane melatonin receptor on neurosecretory cells in the hypothalamus and on hormone secreting cells of the anterior pituitary gland stimulated a great deal of investigation which has failed to prove the involvement of these receptors in the processes by which melatonin influences reproductive physiology. The recent identification of nuclear melatonin receptors as well as the nonreceptor-mediated actions of the indole are currently being examined as to their association with reproductive function.
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PMID:Functional pleiotropy of the neurohormone melatonin: antioxidant protection and neuroendocrine regulation. 855 71

One of the mechanisms proposed to explain lens opacification is the oxidation of crystallins, either by radiation or reactive oxygen species (ROS). It has been shown that melatonin has both an anti-peroxidative effect on several tissues and a scavenger effect on ROS. The purpose of this study was to determine the antioxidant role of melatonin (5 mg/kg/day) against radiation-induced cataract in the lens after total-cranium irradiation of rats with a single dose of 5 Gy. Sprague-Dawley rats were divided into four groups. Control group received neither melatonin nor irradiation. Irradiated rats (IR) and melatonin+irradiated rats (IR+Mel) groups were exposed to total cranium irradiation of 5 Gy in a single dose by using a cobalt-60 teletherapy unit. IR+Mel and melatonin (Mel) groups were administered 5 mg/kg melatonin daily by intraperitoneal injections during ten days. Chylack's cataract classification was used in this study. At the end of the 10th day, the rats were killed and their eyes were enucleated to measure the antioxidant enzymes i.e. the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and lipid peroxidation level (malondialdehyde (MDA)). Irradiation significantly increased the MDA level, as an end product of lipid peroxidation, and also significantly decreased SOD and GSH-Px activity, emphasizing the generation of increased oxidative stress. Rats injected with melatonin only did not cause cataract formation. Melatonin supplementation with irradiation significantly increased the activity of SOD and GSH-Px enzymes and significantly decreased the MDA level. Total cranium irradiation of 5 Gy in a single dose enhanced cataract formation, and melatonin supplementation protected the lenses from radiation-induced cataract formation. Our results suggest that supplementing cancer patients with adjuvant therapy of melatonin may reduce patients suffering from toxic therapeutic regimens such as chemotherapy and/or radiotherapy and may provide an alleviation of the symptoms due to radiation-induced organ injuries.
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PMID:Radioprotective effects of melatonin on radiation-induced cataract. 1598 47

Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine with a range of antioxidative properties. Melatonin is endogenously produced in the eye and in other organs. Current evidence suggests that melatonin may act as a protective agent in ocular conditions such as photo-keratitis, cataract, glaucoma, retinopathy of prematurity and ischemia/reperfusion injury. These diseases are sight-threatening and they currently remain, for the most part, untreatable. The pathogenesis of these conditions is not entirely clear but oxidative stress has been proposed as one of the causative factors. Elevated levels of various reactive oxygen and nitrogen species have been identified in diseased ocular structures. These reactants damage the structure and deplete the eye of natural defense systems, such as the antioxidant, reduced glutathione, and the antioxidant enzyme superoxide dismutase. Oxidative damage in the eye leads to apoptotic degeneration of retinal neurons and fluid accumulation. Retinal degeneration decreases visual sensitivity and even a small change in the fluid content of the cornea and crystalline lens is sufficient to disrupt ocular transparency. In the eye, melatonin is produced in the retina and in the ciliary body. Continuous regeneration of melatonin in the eye offers a frontier antioxidative defense for both the anterior and posterior eye. However, melatonin production is minimal in newborns and its production gradually wanes in aging individuals as indicated by the large drop in circulating blood concentrations of the indoleamine. These individuals are possibly at risk of contracting degenerative eye diseases that are free radical-based. Supplementation with melatonin, a potent antioxidant, in especially the aged population should be considered as a prophylaxis to preserve visual functions. It may benefit many individuals worldwide, especially in countries where access to medical facilities is limited.
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PMID:Protective effects of melatonin in experimental free radical-related ocular diseases. 1644 46

Melatonin (N-acetyl-5-methoxytryptamine) prevents oxidative stress-induced cataract development, and previous studies have suggested that the ocular lens synthesizes melatonin. In the present study, we examined whether two key enzymes in melatonin biosynthesis, arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), are expressed in the lens of adult male rats. Reverse transcriptase-polymerase chain reaction analyses demonstrated that both AANAT and HIOMT mRNAs are expressed in the lens. Western blotting for AANAT protein showed that the lens, like the pineal gland, contains this enzyme protein with a molecular mass of 24 kDa. Immunohistochemistry revealed that AANAT protein is localized to the lens cortical fiber cells. Serotonin, which is a substrate for AANAT and a melatonin precursor, was also found in this region. These findings demonstrate that the lens expresses AANAT and HIOMT, and suggest that the cortical fiber cells are the main melatonin-synthesizing sites in the lens. Locally synthesized melatonin in the lens cortical fiber cells may protect the lens itself from cataract development.
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PMID:Expression and cellular localization of melatonin-synthesizing enzymes in the rat lens. 1719 43

Melatonin (Mel) is a hormone synthesized mainly by the pineal gland. The principal function of Mel in the body involves the control of circadian and seasonal rhythms. Moreover, numerous reports document its anti-oxidative properties. Skin and eyes are particularly sensitive to the noxious influences exerted by UV exposure. The most dangerous radiation of the UVB (ultraviolet-B) and UVA (ultraviolet-A) range induces the formation of reactive oxygen species and thus stimulates the apoptosis of exposed cells. In numerous in vivo and in vitro studies, Mel produced in the skin and eye has been found to protect against the sequelae of UVB- and UVA-induced oxidative stress. In in vitro studies involving UVB irradiation of keratinocytes, fibroblasts, and leukocytes, Mel applied in both pharmacological (10(-3) and 10(-4 )M) and physiological doses (10(-7) and 10(-9) M) decreased the fraction of damaged cells. A similar pattern of Mel action at various doses of Mel probably reflected the presence of melatonin receptors (mainly MT1 receptors) in skin and eye cells. Moreover, intraperitoneally administered Mel or Mel applied to the skin before UVB exposure protects against the development of cataract and erythema, respectively. Thus only intracellular Mel may protect cells against the effects of UVB exposure. Although there are numerous reports describing the effects of UVA on cells of the skin and eye, no studies have described the anti-oxidative properties of Mel in relation to UVA-irradiated cells.
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PMID:[The protective role of melatonin in the course of UV exposure]. 1821 65

Although melatonin is approved only for the treatment of jet-lag syndrome and some types of insomnia, clinical data suggest that it is effective in the adjunctive therapy of osteoporosis, cataract, sepsis, neurodegenerative diseases, hypertension, and even cancer. Melatonin also modulates the electrical activity of neurons by reducing glutamatergic and enhancing GABA-ergic neurotransmission. The indoleamine may also be metabolized to kynurenic acid, an endogenous anticonvulsant. Finally, the hormone and its metabolites act as free radical scavengers and antioxidants. The vast majority of experimental data indicates anticonvulsant properties of the hormone. Melatonin inhibited audiogenic and electrical seizures, as well as reduced convulsions induced by pentetrazole, pilocarpine, L-cysteine and kainate. Only a few studies have shown direct or indirect proconvulsant effects of melatonin. For instance, melatonin enhanced low Mg2+-induced epileptiform activity in the hippocampus, whereas melatonin antagonists delayed the onset of pilocarpine-induced seizures. However, the relatively high doses of melatonin required to inhibit experimental seizures can induce some undesired effects (e.g., cognitive and motor impairment and decreased body temperature). In humans, melatonin may attenuate seizures, and it is most effective in the treatment of juvenile intractable epilepsy. Its additional benefits include improved physical, emotional, cognitive, and social functions. On the other hand, melatonin has been shown to induce electroencephalographic abnormalities in patients with temporal lobe epilepsy and increase seizure activity in neurologically disabled children. The hormone showed very low toxicity in clinical practice. The reported adverse effects (nightmares, hypotension, and sleep disorders) were rare and mild. However, more placebo-controlled, double-blind randomized clinical trials are needed to establish the usefulness of melatonin in the adjunctive treatment of epilepsy.
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PMID:Melatonin in experimental seizures and epilepsy. 2144 6

Melatonin is a neurohormone known to modulate a wide range of circadian functions, including sleep. The synthesis and release of melatonin from the pineal gland is heavily influenced by light stimulation of the retina, particularly through the intrinsically photosensitive retinal ganglion cells. Melatonin is also synthesised within the eye, although to a much lesser extent than in the pineal gland. Melatonin acts directly on ocular structures to mediate a variety of diurnal rhythms and physiological processes within the eye. The interactions between melatonin, the eye, and visual function have been the subject of a considerable body of recent research. This review is intended to provide a broad introduction for eye-care practitioners and researchers to the topic of melatonin and the eye. The first half of the review describes the anatomy and physiology of melatonin production: how visual inputs affect the pineal production of melatonin; how melatonin is involved in a variety of diurnal rhythms within the eye, including photoreceptor disc shedding, neuronal sensitivity, and intraocular pressure control; and melatonin production and physiological roles in retina, ciliary body, lens and cornea. The second half of the review describes clinical implications of light/melatonin interactions. These include light exposure and photoreceptor contributions in melatonin suppression, leading to consideration of how blue blockers, cataract, and light therapy might affect sleep and mood in patients. Additionally, the interactions between melatonin, sleep and refractive error development are discussed. A better understanding of environmental factors that affect melatonin and subsequent effects on physiological processes will allow clinicians to develop treatments and recommend modifiable behaviours to improve sleep, increase daytime alertness, and regulate ocular and systemic processes related to melatonin.
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PMID:Ocular and systemic melatonin and the influence of light exposure. 3007 78