title: Chloride secretion induced by rotavirus is oxidative stress-dependent and inhibited by Saccharomyces boulardii in human enterocytes.
abstract: Rotavirus (RV) infection causes watery diarrhea via multiple mechanisms, primarily chloride secretion in intestinal epithelial cell. The chloride secretion largely depends on non-structural protein 4 (NSP4) enterotoxic activity in human enterocytes through mechanisms that have not been defined. Redox imbalance is a common event in cells infected by viruses, but the role of oxidative stress in RV infection is unknown. RV SA11 induced chloride secretion in association with an increase in reactive oxygen species (ROS) in Caco-2 cells. The ratio between reduced (GSH) and oxidized (GSSG) glutathione was decreased by RV. The same effects were observed when purified NSP4 was added to Caco-2 cells. N-acetylcysteine (NAC), a potent antioxidant, strongly inhibited the increase in ROS and GSH imbalance. These results suggest a link between oxidative stress and RV-induced diarrhea. Because Saccharomyces boulardii (Sb) has been effectively used to treat RV diarrhea, we tested its effects on RV-infected cells. Sb supernatant prevented RV-induced oxidative stress and strongly inhibited chloride secretion in Caco-2 cells. These results were confirmed in an organ culture model using human intestinal biopsies, demonstrating that chloride secretion induced by RV-NSP4 is oxidative stress-dependent and is inhibited by Sb, which produces soluble metabolites that prevent oxidative stress. The results of this study provide novel insights into RV-induced diarrhea and the efficacy of probiotics.
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Buccigrossi
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Laudiero
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Russo
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy.
authors.forename: Erasmo
authors.initials: E
authors.lastname: Miele
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy.
authors.forename: Morena
authors.initials: M
authors.lastname: Sofia
authors.affiliation: Department of Veterinary Public Health & Food Safety, Viral Zoonoses Unit, Istituto Superiore di Sanità Rome - Italy, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Monini
authors.affiliation: Department of Veterinary Public Health & Food Safety, Viral Zoonoses Unit, Istituto Superiore di Sanità Rome - Italy, Rome, Italy.
authors.forename: Franco Maria
authors.initials: FM
authors.lastname: Ruggeri
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Guarino
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002712:Chlorides / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D005978:Glutathione / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology / Q000821:virology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012401:Rotavirus / Q000378:metabolism*; D012400:Rotavirus Infections / Q000378:metabolism / Q000382:microbiology* / Q000821:virology; D012440:Saccharomyces / Q000378:metabolism*; D014118:Toxins, Biological / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002712:Chlorides; D006023:Glycoproteins; C081369:NS28 protein, rotavirus; D017382:Reactive Oxygen Species; D014118:Toxins, Biological; D017361:Viral Nonstructural Proteins; D005978:Glutathione; D000111:Acetylcysteine