title: Safety, bioavailability and mechanism of action of nitric oxide to control Bovine Respiratory Disease Complex in calves entering a feedlot.
abstract: Bovine Respiratory Disease Complex (BRDc), a multi-factorial disease, negatively impacts the cattle industry. Nitric oxide (NO), a naturally occurring molecule, may have utility controlling incidence of BRDc. Safety, bioavailability, toxicology and tolerance/stress of administering NO to cattle is evaluated herein. Thirteen, crossbred, multiple-sourced, commingled commercial weaned beef calves were treated multiple times intranasally over a 4 week period with either a nitric oxide releasing solution (treatment) or saline (control). Exhaled NO, methemoglobin percent (MetHg) and serum nitrites demonstrated biological availability as a result of treatment. Cortisol levels, tissue nitrites, behavior and gross and macroscopic pathology of organs were all normal. Moreover, preliminary in vitro studies using Mannheimia haemolytica, Infectious Bovine Rhinotracheitis, Bovine Parainfluenza-3 and Bovine Respiratory Syncytial Virus, suggest a potential explanation for the previously demonstrated efficacy for BRDc. These data confirm the bioavailability, safety and lack of residual of NO treatment to cattle, along with the bactericidal and virucidal effects.
authors.affiliation: Faculty of Medicine, Respiratory Division, University of British Columbia, Vancouver, BC, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Regev-Shoshani
authors.affiliation: Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Vimalanathan
authors.affiliation: Department of Natural Resource Sciences, Thompson Rivers University, Kamloops, BC, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Prema
authors.affiliation: Department of Natural Resource Sciences, Thompson Rivers University, Kamloops, BC, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Church
authors.affiliation: Department of Biological Sciences, Thompson Rivers University, Kamloops, BC, Canada.
authors.forename: M W
authors.initials: MW
authors.lastname: Reudink
authors.affiliation: Animal Pathology Services (APS) Ltd., 18208 Ellerslie Road, Edmonton, Alberta, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Nation
authors.affiliation: Faculty of Medicine, Respiratory Division, University of British Columbia, Vancouver, BC, Canada. Electronic address: miller42@mail.ubc.ca.
authors.forename: C C
authors.initials: CC
authors.lastname: Miller
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048090:Bovine Respiratory Disease Complex / Q000188:drug therapy* / Q000382:microbiology / Q000821:virology; D002417:Cattle; D006651:Histocytochemistry / Q000662:veterinary; D006854:Hydrocortisone / Q000097:blood; D008168:Lung / Q000382:microbiology* / Q000821:virology*; D008706:Methemoglobin / Q000032:analysis; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009573:Nitrites / Q000097:blood; D014741:Video Recording
chemical_list: D009573:Nitrites; D009569:Nitric Oxide; D008706:Methemoglobin; D006854:Hydrocortisone
keywords: Antimicrobial; Bovine Respiratory Disease; Nitric oxide; Shipping fever; Sustainability; Undifferentiated fever