A considerable amount of clinical and experimental evidence exists suggesting the involvement of reactive oxygen substances (ROS) in the aetiology of uveitis. The activated phagocytic system of polymorphonuclear leucocytes in uveitis is involved in the generation of ROS. In addition to their direct free radical scavenging action, aprotinin, melatonin and vitamin C are known to protect against oedema formation and can preserve plasma membrane fluidity and free radical production. Histological changes in the retina that occur during uveitis are not well explained. The purpose of this study was to determine whether vitamin C, aprotinin and melatonin can protect the retina from damage accompanying experimental uveitis (EU). Thirty adult male guinea pigs were divided into five groups of six animals each. The first group was used as control. The right eyes of groups 2, 3, 4 and 5 received an intravitreal injection of bovine serum albumin for induction of experimental uveitis. At the same time and also on the consecutive third day, groups 3, 4 and 5 received intraperitoneal injections of vitamin C (ascorbic acid, 100 mg kg(-1) body wt), aprotinin (20,000 kIU kg(-1) body wt) and melatonin (10 mg kg(-1) body wt), respectively. The animals were killed on the sixth day. The average thickness of the retina and inner plexiform layer for each eye was measured in sagittal section near the optic nerve and expressed in microns. The thickness of the retina and inner plexiform layer in the control group was significantly (p < 0.01) lower than in the group EU as compared with the group EU plus vitamin C, group EU plus aprotinin, group EU plus melatonin (p < 0.05). The thicknesses of the retina and inner plexiform layer in group EU plus vitamin C, group EU plus aprotinin and group EU plus melatonin were significantly (p < 0.01) lower than that in the group EU. The difference in thickness of the retina and inner plexiform layer among the groups 3, 4 and 5 was not significant (p > 0.05). In conclusion, this study demonstrated that oedematous effects of EU on the retina were reduced by the administration of intraperitoneal vitamin C, aprotinin and melatonin, i.e. these antioxidants had significant protective effects on the retina of guinea pigs against oedematous damage in EU. However, the reductive effect of vitamin C on EU was greater than that of aprotinin and melatonin. The intraperitoneal vitamin C, aprotinin and melatonin supplementations may strengthen the antioxidant defence system because of decreased ROS, and these agents may play a role in treating uveitis.
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http://dx.doi.org/10.1002/cbf.1105 | DOI Listing |
Crit Rev Toxicol
September 2012
Temasek Laboratories, National University of Singapore, Singapore.
Victims exposed to sulfur mustard (HD) in World War I and Iran-Iraq war, and those suffered occupational or accidental exposure have endured discomfort in the respiratory system at early stages after exposure, and marked general physical deterioration at late stages due to pulmonary fibrosis, bronchiolitis obliterans or lung cancer. At molecule levels, significant changes of cytokines and chemokines in bronchoalveolar lavage and serum, and of selectins (in particular sE-selectin) and soluble Fas ligand in the serum have been reported in recent studies of patients exposed to HD in Iran-Iraq war, suggesting that these molecules may be associated with the pathophysiological development of pulmonary diseases. Experimental studies in rodents have revealed that reactive oxygen and nitrogen species, their product peroxynitrite (ONOO(-)), nitric oxide synthase, glutathione, poly (adenosine diphosphate-ribose) polymerase, activating protein-1 signaling pathway are promising drug targets for preventing HD-induced toxicity, whereas N-acetyl cysteine, tocopherols, melatonin, aprotinin and many other molecules have been proved to be effective in prevention of HD-induced damage to the respiratory system in different animal models.
View Article and Find Full Text PDFPulm Pharmacol Ther
February 2011
Department of Pediatrics, Division of Neonatology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 1 Robert Wood Johnson Place, New Brunswick, NJ 08903, USA.
Sulfur mustard (SM) is highly toxic to the lung inducing both acute and chronic effects including upper and lower obstructive disease, airway inflammation, and acute respiratory distress syndrome, and with time, tracheobronchial stenosis, bronchitis, and bronchiolitis obliterans. Thus it is essential to identify effective strategies to mitigate the toxicity of SM and related vesicants. Studies in animals and in cell culture models have identified key mechanistic pathways mediating their toxicity, which may be relevant targets for the development of countermeasures.
View Article and Find Full Text PDFActa Ophthalmol Scand
February 2006
Department of Histology and Embryology, Izzet Baysal Medical Faculty, Abant Izzet Baysal University, Bolu, Turkey.
Purpose: To observe ultrastructural changes and leptin expression in the guinea pig eye during experimental uveitis (EU) and the effects of vitamin E, melatonin and aprotinin on leptin expression.
Methods: Thirty male guinea pigs were randomly classified into five groups. Group 1 was the control group.
Cell Biochem Funct
March 2005
Department of Ophthalmology, Medical Faculty, Abant Izzet Baysal University, Bolu, Turkey.
A considerable amount of clinical and experimental evidence exists suggesting the involvement of reactive oxygen substances (ROS) in the aetiology of uveitis. The activated phagocytic system of polymorphonuclear leucocytes in uveitis is involved in the generation of ROS. In addition to their direct free radical scavenging action, aprotinin, melatonin and vitamin C are known to protect against oedema formation and can preserve plasma membrane fluidity and free radical production.
View Article and Find Full Text PDFJ Dairy Sci
March 2002
Dairy and Swine Research and Development Centre, Agriculture Agri-Food Canada, Lennoxville, Quebec.
The effect of several antioxidants and a proteinase inhibitor on bovine neutrophil-induced mammary epithelial cell damage was investigated using an in vitro model of co-culturing bovine neutrophils and MAC-T cells, a mammary epithelial cell line. Epithelial cell damages were evaluated by measuring lactate dehydrogenase activity in culture media and by morphological observations of cells after acridine orange staining. Activation of neutrophils with Escherichia coli lipopolysaccharide and phorbol 12-myristate 13-acetate caused superoxide and gelatinase release in media.
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