title: Serum-derived bovine immunoglobulin/protein isolate in the alleviation of chemotherapy-induced mucositis.
abstract: BACKGROUND
  Gastrointestinal (GI) mucositis caused by chemotherapy is associated with diarrhoea and intestinal barrier disruption caused by apoptosis, immune dysfunction and microbiome alterations. Serum-derived bovine immunoglobulin/protein isolate (SBI) has been shown to manage HIV-associated enteropathy and irritable bowel syndrome with diarrhoea (IBS-D). We investigated in a rat model whether SBI was effective in alleviating symptoms of irinotecan-induced GI mucositis.
  
  
  METHODS
  Animals were gavaged with 250 or 500 mg/kg of SBI twice daily for 4 days, before intraperitoneal administration of 200 mg/kg irinotecan. Twice daily gavaging of SBI continued for 6 days post-irinotecan. Animals were monitored for bodyweight changes and incidence of diarrhoea and clinical symptoms of stress. Tissues and blood samples were collected at necropsy 6 h, and 2, 4 and 6 days post-irinotecan. H&E-stained colon and jejunum were analysed for histological damage.
  
  
  RESULTS
  The overall incidence, severity and duration of diarrhoea, and clinical symptoms of mucositis were decreased in irinotecan-treated animals that had received SBI. Animals receiving 500 mg/kg SBI also tended to lose less bodyweight than animals treated only with irinotecan (P > 0.10). SBI-gavaged animals had less pronounced irinotecan-induced changes in neutrophil (P = 0.04959) and lymphocyte (P = 0.0035) levels, and lower tissue damage scores than those receiving irinotecan alone (P < 0.0001).
  
  
  CONCLUSIONS
  Twice daily oral gavage of SBI was well-tolerated and reduced the incidence, severity and duration of irinotecan-induced mucositis. SBI was associated with less pronounced changes in inflammatory cell levels and tissue damage to colon and jejunum. Ongoing experiments aim to investigate the mechanisms of SBI-associated gastrointestinal protection.
authors.affiliation: Mucositis Research Group, School of Medicine, Faculty of Health Sciences, University of Adelaide, Level 4 Hanson Institute Building, Frome Road, Adelaide, SA, 5000, Australia. emma.bateman@adelaide.edu.au.
authors.forename: Emma
authors.initials: E
authors.lastname: Bateman
authors.affiliation: Entera Health Inc, Cary, NC, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Weaver
authors.affiliation: Entera Health Inc, Cary, NC, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Klein
authors.affiliation: Mucositis Research Group, School of Medicine, Faculty of Health Sciences, University of Adelaide, Level 4 Hanson Institute Building, Frome Road, Adelaide, SA, 5000, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Wignall
authors.affiliation: Mucositis Research Group, School of Medicine, Faculty of Health Sciences, University of Adelaide, Level 4 Hanson Institute Building, Frome Road, Adelaide, SA, 5000, Australia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Wozniak
authors.affiliation: Mucositis Research Group, School of Medicine, Faculty of Health Sciences, University of Adelaide, Level 4 Hanson Institute Building, Frome Road, Adelaide, SA, 5000, Australia.
authors.forename: Erin
authors.initials: E
authors.lastname: Plews
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
authors.forename: Bronwen
authors.initials: B
authors.lastname: Mayo
authors.affiliation: School of Medical Sciences, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Imogen
authors.initials: I
authors.lastname: White
authors.affiliation: Mucositis Research Group, School of Medicine, Faculty of Health Sciences, University of Adelaide, Level 4 Hanson Institute Building, Frome Road, Adelaide, SA, 5000, Australia.|SA Cancer Service, Royal Adelaide Hospital, Adelaide, SA, Australia.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Keefe
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000633:toxicity; D001798:Blood Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D002417:Cattle; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control; D003967:Diarrhea / Q000139:chemically induced; D004751:Enteritis / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D007136:Immunoglobulins / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D000077146:Irinotecan; D007579:Jejunal Diseases / Q000139:chemically induced / Q000517:prevention & control; D052016:Mucositis / Q000139:chemically induced / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats
chemical_list: D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D001798:Blood Proteins; D007136:Immunoglobulins; D000077146:Irinotecan; D002166:Camptothecin
keywords: Animal model; Enteropathy; Medical food; Mucositis; Serum-derived bovine immunoglobulin/protein isolate (SBI)