cortisol-succinate--sodium-salt and Cataract

The etiopathogenesis of steroid-induced cataracts is unknown. One hypothesis is that the higher reactive oxygen species (ROS) levels play an important role in the pathogenesis of several disorders, including the evolution of cataracts. This study investigated the antioxidant effects of piperine in our steroid-induced chick embryo lens model.. The study included 36 specific pathogen-free (SPF) fertilized eggs divided into six groups: phosphate buffer saline (PBS, pH 7.4 Saline Solution (0.9%) isotonic) group (G1), hydrocortisone succinate sodium (HC)-treated group (G2), 100 mg/kg piperine and HC treated group (G3), 50 mg/kg piperine and HC treated group (G4), 25 mg/kg piperine and HC treated group (G5), and 10 mg/kg piperine and HC treated group (G6). On the 15th day of incubation, the SPF eggs in the six groups were removed from the incubator; all were injected using insulin injectors into the chorioallantoic membrane. On day 17, all of the chick embryos were removed from the eggs and all lenses were dissected from the embryos. Cataract formation was evaluated in all lenses, and total antioxidant status (TAS), total oxidant status (TOS), reduced glutathione (GSH), and lipid peroxidation (MDA, malondialdehyde) levels were measured in all lens.. The lenses in the G1 group had higher levels of GSH and TAS (p < 0.01), and lower levels of MDA and TOS than the G2 group (p < 0.05 and p < 0.01, respectively). Group 3 had higher levels of GSH and TAS (p < 0.001 and p < 0.001 respectively), and lower levels of MDA and TOS than the G2 group (p < 0.01 and p < 0.001, respectively).. Steroid therapy causes a decrease in GSH and TAS levels and an increase in TOS and MDA levels in lens tissues, indicating increased oxidative stress. Piperine exerts its effects as an antioxidant substance, in increasing doses.

Topics: Alkaloids; Animals; Antioxidants; Benzodioxoles; Cataract; Chick Embryo; Glutathione; Hydrocortisone; Lens, Crystalline; Malondialdehyde; Piperidines; Polyunsaturated Alkamides

The present study evaluated the protective action of calcium dobesilate (CDO) in various experimental models of cataract. CDO was studied in hydrocortisone-induced cataract in developing chick embryos and selenite-induced cataract in pups. CDO anti-cataract activity was also evaluated after oral and topical application as eye drops in galactose (30%) fed rats. This study was further extended to evaluate the intraocular penetration of a single dose of 1% CDO (50 microL) in rabbits. CDO exhibited significant protection against cataract in experimental models and considerable penetration after single topical application. Anti-cataract activity may be due to its antioxidant as well as aldose reductase inhibitor properties. Further studies are in progress to evaluate its clinical efficacy in diabetic cataract.

Topics: Administration, Oral; Administration, Topical; Aldehyde Reductase; Animals; Calcium Dobesilate; Cataract; Chick Embryo; Disease Models, Animal; Female; Galactose; Hemostatics; Hydrocortisone; Male; Ophthalmic Solutions; Oxidative Stress; Rabbits; Rats; Rats, Wistar; Sodium Selenite

To determine the reversible effect of insulin on glucocorticoid (GC)-induced cataract formation in relation to systemic metabolic changes in the developing chick embryo.. Hydrocortisone sodium succinate (HC; 0.25 micromoles) was administered to 15-day-old embryos followed by administration of long-acting recombinant human insulin, 4 and 28 hours later. At the indicated time after HC administration, the incidence of cataractous lenses and any changes in the components of the lenses, liver, and blood were determined.. At 48 hours after HC administration, the following observations were made: opacification of lenses; an elevation of glucose and lipids in the blood and lenses; an increase in lipid peroxide (LPO) in the blood, liver, and lenses; a decrease in glutathione (GSH) in the lens and liver (at 24 hours after HC administration); and a depletion of adenosine triphosphate (ATP) in the liver. These changes in response to HC administration were reversed by a double application of insulin.. Insulin antagonizes GC-induced gluconeogenesis, stimulates glycolysis, and ultimately leads to recovery of decreased activity in the citric acid cycle. The restoration of ATP by the recovered citric acid cycle may facilitate de novo synthesis of GSH, which in turn may diminish GC-induced elevation of LPO in the liver. Thus, the metabolic changes in response to HC-accelerated gluconeogenesis in the liver, which can be reversed by insulin, are likely to produce oxidative stress that leads to cataract formation. GC-induced metabolic changes in the liver, which are antagonized by insulin, may relate to production of one of the risk factors for cataract formation.

Topics: Adenosine Triphosphate; Animals; Cataract; Chick Embryo; Diabetes Mellitus, Experimental; Glucocorticoids; Gluconeogenesis; Glucose; Glutathione; Glycolysis; Hydrocortisone; Insulin; Ketone Bodies; Lens, Crystalline; Lipid Metabolism; Lipid Peroxides; Liver; Recombinant Proteins

Administration of glucocorticoids induces transient cataract in 15-day-old chick embryos within 48 hr, and the opaque lens again becomes clear within the subsequent 48 hr. Oxidative stress is likely to be involved in the process of cataract formation, resulting in the appearance of numerous vacuoles around the perinuclear region. Chick lens contained low amounts of glycosphingolipids, which mainly consists of GM3, GD3, sialyl-LewisX gangliosides and glucosylceramide. Most lens gangliosides were immunohistochemically detected in lens epithelia, annular pads and developing fibers, but not in perinuclear and nuclear regions. Since cell surface gangliosides, for example GM3 and sialyl-LewisX gangliosides, are involved in cell adhesion, weak cell-to-cell interactions in the perinuclear and nuclear regions may allow vacuole formation in steroid-induced cataractogenesis.

Topics: Animals; Anti-Inflammatory Agents; Cataract; Chick Embryo; Chromatography, Thin Layer; Gangliosides; Glycosphingolipids; Hydrocortisone; Immunoenzyme Techniques; Lens, Crystalline

In this paper various changes in glutathione level, which were influenced by balance of its synthesis, degradation, transport and utilization, were analysed in chick embryos administered with glucocorticoid (GC) or buthionine sulfoximine (BSO; an inhibitor of glutathione synthesis). When BSO (30 mumol egg-1) was administered twice to chick embryos on day 14 and 15, the GSH in both the lens and the liver decreased to 15-20% and 30-40% of the age-matched control level, respectively, between 24 and 48 hr after the second treatment, then began to recover. Although this decline in the GSH level in these tissues was greater and more prolonged in embryos treated with BSO than with GC, the former embryos maintained lens transparency even up to 144 hr by a visual examination. However, histological changes in the lens occurred after 96 hr and more significantly 144 hr after second administration of BSO. The changes mainly consisted of pale epithelial cells on the anterior peripheral surface of the lens, irregular height of the epithelial cells at the equator, clefts between the epithelium and the cortex and swelling of almost all the cortical fibers. These observations may suggest that BSO treatment could produce the beginning of a cataract. Embryos with GC-cataract revealed the following changes at 48 hr: loss of transparency, elevation of LPO (TBA-reacting substance) in the lens, the blood and the liver. These were not observed in BSO-treated embryos during the experimental period. The GC-cataract may well depend on the generation of LPO. BSO cataract, having a distinct mechanism compared to that caused by GC, develops more slowly in GSH-depleted lenses. The BSO-treated chick embryos will be a useful model to screen the risk factors which accelerate cataract formation.

Topics: Animals; Anti-Inflammatory Agents; Buthionine Sulfoximine; Cataract; Chick Embryo; Glutathione; Hydrocortisone; Lens, Crystalline; Lipid Peroxides; Liver; Microscopy, Electron

In order to develop an effective screening model for anticataract agents, we examined the age dependence of cataract induction by glucocorticoid in developing chick embryos. Hydrocortisone sodium succinate (0.25 mumol) was administered to chick embryos on day 15 (15-day-old) and cataract formation was examined 48 hr later. Administration earlier than on day 13 or later than on day 15 was a little or ineffective. These results indicate that the formation of glucocorticoid-induced cataract in developing chick embryos depends on developing stages. The embryos treated with hydrocortisone sodium succinate on day 15 decreased GSH amount in the lens, approximately 50% of the control in 48hr. However, the embryos treated at other ages, in which cataract was not induced, showed little or no decrease of GSH. The cataract formation in chick embryos appeared to depend on structure of steroid and was due to biological activities of glucocorticoids. Since cataract is easily produced in a reproducible manner with high incidence by glucocorticoid, our chick embryo model will be a valuable model system for screening anticataract agents.

Topics: Animals; Anti-Inflammatory Agents; Cataract; Chick Embryo; Disease Models, Animal; Drug Evaluation, Preclinical; Glutathione; Hydrocortisone; Incidence; Lens, Crystalline; Reproducibility of Results; Structure-Activity Relationship

When 0.25 mumol of hydrocortisone succinate sodium (HC) was administered to 15-day-old hen's fertile eggs, almost all lenses of the embryos became cataractous with stages IV-V (> 90%) 48 h after the treatment. However, a triple application of propylene glycol (1.5 mmol/egg) at 3, 10 and 20 h after HC treatment effectively prevented the HC-induced cataract formation (I: 84%, II: 12%, III: 4%, IV-V: 0%) and repressed the decline of glutathione and the elevation of lipid peroxide in the lens caused by HC. Propylene glycol is metabolized to lactate and pyruvate producing NADH and is known to possess protective activities against X-ray irradiation. These properties have modified the HC-induced effects and decreased the production of oxidative stress in ovo, protecting the lens from losing its transparency after HC administration. Furthermore, a marked elevation of glucose in cataractous lenses noted after HC administration was not directly involved in opacification of the lenses.

Topics: Animals; Cataract; Chick Embryo; Glutathione; Hydrocortisone; Incidence; Lens, Crystalline; Lipid Peroxides; Liver; Propylene Glycol; Propylene Glycols

The preventive effect of SA3443 [(4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid] against glucocorticoid-induced cataract of developing chick embryos was studied. When hydrocortisone succinate sodium (HC: 0.25 mumol per egg) was administered to 15-day-old embryos, almost all lenses became opaque (stage I:O%, II: 2.5 +/- 4.6%, III: 5 +/- 5.4%, IV-V 92.5 +/- 7.1%) at 48 hr after the treatment. However, a double application of SA3443 (10 mumol per egg) at 3 and 10 hr after HC treatment effectively prevented the cataract formation (stage I: 52.8 +/- 13.7%, II: 11.6 +/- 6.3%, III: 22.9 +/- 8.9%, IV-V: 13.9 +/- 11.0%) and diminished the decline in glutathione in the lens at 48 hr and in the liver at 24 hr after HC administration. The cleavage of the cyclic disulfide bond of SA3443 did not occur in the lens homogenate but in the liver homogenate. These results suggest that the appearance of sulfhydryl residue in the liver may contribute to the anticataract effects by representing radical scavenger activities.

Topics: Animals; Azocines; Cataract; Chick Embryo; Disulfides; Glutathione; Hydrocortisone; Lens, Crystalline; Liver

Nishigori et al. reported a transient cataract model after administering glucocorticoid to a 15-day-old chick. Biochemically, the mechanism of onset of this cataract was though to be related to damage caused by the formation of oxidative stresses and by a protein-water phase separation. There appear to be no reports on changes in the fine structure. After hydrocortisone succinate sodium was administered to 15-day-old chick embryos, the lenses were removed at 12, 24, 30, 48, 72 and 96 h and put in 4% glutaraldehyde. The specimens were examined by light, transmission and scanning electron microscopy. Twelve to 24 h after administration to chick embryos, lens fibers containing electron-dense cytoplasm began to appear in the bow area of the equator and were still present thereafter. Thirty to 48 h after administration, numerous vacuoles of varying sizes began to appear in the lens in sites corresponding to the opaque region. These vacuoles, ranging from 2 to 8 microns in diameter, were distributed in the intercellular spaces between the lens fibers. The vacuoles had disappeared by 96 h after administration, but during that period, the height of the epithelial cells in the equatorial region and the elongation of the equatorial lens fibers had become irregular. Transient opacity was due to the presence of vacuoles of various sizes, occurring in the intercellular space between the lens fibers around the lens nucleus. Moreover, the effect of glucocorticoid administration was noted in the lens epithelium and the lens fibers in the equatorial region.

Topics: Animals; Cataract; Chick Embryo; Chickens; Disease Models, Animal; Epithelium; Hydrocortisone; Lens Nucleus, Crystalline; Lens, Crystalline; Microscopy, Electron, Scanning; Vacuoles

Glucocorticoid-induced cataract formation appears to proceed via oxidation or peroxidation steps possibly caused by multiple activities of glucocorticoid in the living system. Attempts were made to modify GC-induced metabolic changes and prevent cataract formation using intermediates of the citric acid cycle. The compounds were applied to the embryos at 3, 10 and 20 hr after the administration of hydrocortisone succinate sodium (HC:0.25 mumol/egg) to 15-day-old eggs. At 48 hr after HC treatment the lenses were classified and analyzed. Almost all lenses were classified as stage IV-V (greater than 94%). However, the application of sodium isocitrate (IC:15 mumol/egg) which was the most potent among several intermediates tested showed a significant preventive effect against cataract formation. The administration of IC prevented the decline of GSH, the elevations of LPO and reduced the marked elevation of glucose in the lens caused by HC. The IC treatment also diminished the elevation of LPO in blood and liver. The above effects by IC on HC-induced events may be due to the action of IC in preventing the early decline of hepatic GSH caused by HC. Possibly IC was utilized as an intermediate of the citric acid cycle and a substrate for isocitrate dehydrogenase in cytosol to modify GC-induced metabolic changes.

Topics: Animals; Cataract; Chick Embryo; Glucose; Glutathione; Hydrocortisone; Isocitrates; Lens, Crystalline; Lipid Peroxides; Liver

When 15-day-old developing chick embryos were administered hydrocortisone hemisuccinate sodium (HC:0.25 mumol per egg) the concentration of glucose in both the aqueous humor and the vitreous body began to increase significantly after 3 hr and reached 24.4 +/- 0.3 mM and 22.3 +/- 0.9 mM, respectively, at 48 hr. Thereafter, the levels decreased to the control by 100 hr. During the treatment period, the glucose concentration of the control aqueous humor and vitreous body remained at approximately 7.5 mM and 4.3 mM, respectively. These changes in glucose after HC administration were quite different from that of the lens in regard to the extent of increase and the lag time required to produce glucose accumulation. By in vitro and in ovo experiments, it was found that the environment surrounding lens, medium and ocular fluids, greatly influenced the level of lenticular glucose rather than any changes metabolic activities in the lens. A glucose threshold of near 15 mM in milieu was required to promote the accumulation glucose in the lens.

Topics: Animals; Aqueous Humor; Cataract; Chick Embryo; Glucose; Hydrocortisone; Vitreous Body

Topics: Aldosterone; Animals; Cataract; Chick Embryo; Disease Models, Animal; Hydrocortisone

Glucocorticoid administration to developing chick embryos is known to promote cataract formation with a decreasing level of glutathione in the lens. To gain further understanding of this process, the level of ascorbic acid, a biological antioxidant, in the lenses was measured during the course of glucocorticoid treatment. When 0.25 mumol of hydrocortisone hemisuccinate sodium (HC) were administered to 15-day-old chick embryos, the level of ascorbic acid in the lens began to decline after 30 hr and became around 40% of the control value at 48 hr after HC treatment. At this time about 90% of the lenses showed opacity in the nuclear region. However, the level of ascorbic acid in the cataractous lens recovered to the control level at 96 hr, a time when the lens has recovered from cataract formation. A triple application of ascorbic acid (20 mumol/egg) at 3, 10 and 20 hr after HC treatment significantly prevented lens opacification. The administration of ascorbic acid prevented the decline of ascorbic acid content and partially that of glutathione content in the lens caused by HC.

Topics: Animals; Ascorbic Acid; Cataract; Chick Embryo; Glutathione; Hydrocortisone; Lens, Crystalline