title: Copper sulfate pentahydrate reduced epithelial cytotoxicity induced by lipopolysaccharide from enterogenic bacteria.
abstract: The over usage of multiple antibiotics contributes to the emergence of a whole range of antibiotic-resistant strains of bacteria causing enterogenic infections in poultry science. Therefore, finding an appropriate alternative natural substance carrying an antibacterial capacity would be immensely beneficial. It has been previously discovered that the different types of cupric salts, especially copper sulfate pentahydrate (CuSO4·5H2O), to carry a potent bactericidal capacity. We investigated the neutralizing effect of CuSO4·5H2O (6.25μg/ml) on the reactive oxygen species generation, and expression of MyD88, an essential adaptor protein of Toll-like receptor, and NF-κB in three intestinal epithelial cell lines exposed to 50ng/ml lipopolysaccharide. In order to find the optimal cupric sulfate concentration without enteritis-inducing toxicity, broiler chickens were initially fed with water containing 0.4, 0.5, and 1mg/l during a period of 4days. After determination of appropriate dosage, two broiler chickens and turkey flocks with enteritis were fed with cupric compound for 4days. We found that cupric sulfate can lessen the cytotoxic effect of lipopolysaccharide by reducing the reactive oxygen species content (p<0.05). Additionally, the expression of MyD88 and NF-κB was remarkably down-regulated in the presence of lipopolysaccharide and cupric sulfate. The copper sulfate in doses lower than 0.4mg/ml expressed no cytotoxic effect on the liver, kidney, and the intestinal tract while a concentration of 0.5 and 1mg/ml contributed to a moderate to severe tissue injuries. Pearson Chi-Square analysis revealed the copper cation significantly diminished the rate of mortality during 4-day feeding of broiler chicken and turkey with enteritis (p=0.000). Thus, the results briefed above all confirm the potent anti-bactericidal feature of cupric sulfate during the course of enteritis.
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
authors.forename: Adel
authors.initials: A
authors.lastname: Feyzi
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
authors.forename: Aref
authors.initials: A
authors.lastname: Delkhosh
authors.affiliation: Department of Anatomical Science, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hamid Tayefi
authors.initials: HT
authors.lastname: Nasrabadi
authors.affiliation: Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Omid
authors.initials: O
authors.lastname: Cheraghi
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
authors.forename: Mansour
authors.initials: M
authors.lastname: Khakpour
authors.affiliation: Department of Physiology & Biophysics, Case Western Reserve University- School of Medicine, Cleveland, OH, United States.
authors.forename: Mazyar
authors.initials: M
authors.lastname: Barekati-Mowahed
authors.affiliation: Department of Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Sina
authors.initials: S
authors.lastname: Soltani
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Seyede Momeneh
authors.initials: SM
authors.lastname: Mohammadi
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Kazemi
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hassanpour
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Aysa
authors.initials: A
authors.lastname: Rezabakhsh
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: malekins@tbzmed.ac.ir.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Maleki-Dizaji
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: Rahbarghazir@tbzmed.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Rahbarghazi
authors.affiliation: Department of Poultry disease, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Namdarian
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002645:Chickens; D019327:Copper Sulfate / Q000494:pharmacology*; D004751:Enteritis / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary; D004847:Epithelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000633:toxicity*; D008826:Microbial Sensitivity Tests; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D011201:Poultry Diseases / Q000517:prevention & control; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D017382:Reactive Oxygen Species; D019327:Copper Sulfate
keywords: Broiler chickens; Copper sulfate pentahydrate; Intestinal epithelial cells; Lipopolysaccharide; Toll-like receptor signaling