title: Antioxidant supplementation enhances bacterial peritonitis in mice by inhibiting phagocytosis.
abstract: Antioxidants are known to exhibit numerous health benefits including anti-ageing, anti-apoptotic and immuno-stimulatory effects. However, we present the data showing counterproductive effects of therapeutically relevant antioxidants on bacterial clearance by the immune system in a murine peritonitic model. The antioxidants ascorbic acid, glutathione and N-acetylcysteine augmented morbidity and mortality in mice carrying Eshcerichia coli-induced acute bacterial peritonitis. Treatment of peritonitic mice with antioxidants significantly increased their bacterial load in the range of 0.3-2 logs. Antioxidant administration to peritonitic mice resulted in decreased numbers of macrophages, B-cells and dendritic cells at the primary site of infection and increased neutrophil infiltration. Serum TNF-α levels were also decreased in antioxidant-treated peritonitic mice. In vitro experiments showed that antioxidants reduced the phagocytic efficacy of peritoneal macrophages by ~60-75% and also decreased E. coli-induced oxidative burst in macrophages cells. Taken together, our data indicate that the antioxidants increased the severity of peritonitis by decreasing the phagocytic efficiency, oxidative burst, and TNF-α production, and increasing neutrophil infiltration. Based on these results, we propose that antioxidant supplementation during the course of bacterial infection is not recommended as it could be detrimental for the host. In addition, the present study underlines the importance of timing and context of antioxidant administration rather than indiscriminate usage to gain the best possible therapeutic advantage of these redox compounds.
authors.affiliation: Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Goswami
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Nazir M
authors.initials: NM
authors.lastname: Khan
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Checker
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Sandur
authors.affiliation: Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Narendra
authors.initials: N
authors.lastname: Jawali
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000187:drug effects / Q000276:immunology* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D048168:Escherichia coli K12 / Q000187:drug effects / Q000276:immunology; D005260:Female; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D010538:Peritonitis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis / Q000187:drug effects*; D016897:Respiratory Burst / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects
chemical_list: D000975:Antioxidants; D014409:Tumor Necrosis Factor-alpha