title: Melatonin reduces oxidative damage and increases survival of mice infected with Schistosoma mansoni.
abstract: The tropical parasite Schistosoma mansoni causes granulomatous inflammation after its eggs lodge in hepatic portal capillaries. In vitro studies indicate that the host's response involves the production of reactive oxygen species, although whether this occurs in vivo at the site of the infection is unknown. The role of oxidative processes in mice infected with S. mansoni was investigated in the current study using the antioxidant melatonin. In Experiment 1, the survival rate of infected mice with and without daily melatonin (10 mg/kg) administration was determined. After 56 d, 25 of 25 infected mice that were diluent treated had died. In contrast, 22 or 25 infected mice (88%) given melatonin were still alive at 56 d. Of these 22 surviving mice, melatonin injections were continued in 11 while the 11 others were switched to diluent. Within 10 d, 11 of 11 diluent-injected mice that were infected with S. mansoni were dead while 6 of 11 melatonin-treated mice survived. In Experiment 2, S. mansoni-infected mice were treated for 30 d with either melatonin or diluent. Uninfected, untreated mice served as controls. In these mice, the levels of lipid peroxidation (LPO) products, vitamin E, nitric oxide (NO), glutathione (GSH), and superoxide dismutase (SOD) activity in the liver, kidney, and spleen were measured. In the serum, cholesterol levels and liver damage (alkaline phosphatase (ALP), aspartate transaminases (AST), total protein, and albumin) were monitored. In addition, peroxynitrite anion (ONOO(-)) in the liver and kidney and inducible nitric oxide synthase (iNOS) in the spleen were immunocytochemically localized. Also, histopathological changes in the liver, kidney, and spleen were examined. The results documented increased LPO and NO levels and decreased vitamin E, GSH, and SOD activity in the liver, kidney, and spleen of S. mansoni-infected mice. Also, there was an increase in serum cholesterol and evidence of liver damage in the infected mice. Immunohistochemical results indicated positive staining of ONOO(-) in the liver and kidney and positive iNOS staining in the spleen of S. mansoni-infected mice. Histopathological observations revealed granuloma formation in the liver with eosinophil infiltration, a large number of megakaryocytes in the spleen, and degeneration with necrotic cells in some tubules of the kidney cortex in the infected mice. Melatonin administration after S. mansoni infection prevented most of the previously described changes. These results suggest that oxidative processes occur at the site of inflammation and are involved in the damaging effects of schistosomiasis and indicate that free radicals may be a major component of the disease. Likewise, melatonin, presumably due to its antioxidant and free radical scavenging activity, is highly protective against the pathological changes associated with schistosomiasis.
authors.affiliation: Department of Zoology, Faculty of Science, Assiut University, Assiut, Egypt.
authors.forename: Gamal H
authors.initials: GH
authors.lastname: El-Sokkary
authors.forename: Hosam M
authors.initials: HM
authors.lastname: Omar
authors.forename: Abdel-Fattah M M
authors.initials: AF
authors.lastname: Hassanein
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000469:parasitology; D015227:Lipid Peroxidation; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D012550:Schistosoma mansoni / Q000472:pathogenicity*; D013154:Spleen / Q000166:cytology / Q000469:parasitology; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014810:Vitamin E / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D014810:Vitamin E; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D013482:Superoxide Dismutase; D000469:Alkaline Phosphatase; D005978:Glutathione; D008550:Melatonin