title: 28-day repeated dose oral toxicity of human copper-zinc superoxide dismutase from recombinant Pichia pastori in rats.
abstract: Human copper/zinc superoxide dismutase from recombinant Pichia pastori (RH-Cu/Zn-SOD) was orally administered, via gavage, to Sprague-Dawley rats at 500, 1,000, and 2,000 mg/kg body weight/day for 28 days. During the 28-day period, animals were examined for evidence of toxicity; there were no deaths, and in-life physical signs were normal. On day 29, the animals were exsanguinated, examined for gross pathology, and tissues were preserved for histopathology. Although statistical differences were noted in some hematology and clinical chemistry, they were of questionable biological significance. The results of the 28-day oral administration demonstrated a lack of toxicity of RH-Cu/Zn-SOD in rats. There were no treatment-related, toxicologically relevant changes in clinical signs, growth, food consumption, hematology, clinical chemistry, organ weights, or pathology. The no observed adverse effect level was greater than 2,000 mg/kg/day for RH-Cu/Zn-SOD in rats.
authors.affiliation: College of Food and Bioengineering, South China University of Technology, Guangzhou, China. zhuliang@scut.edu.cn
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.forename: Ying-Juan
authors.initials: YJ
authors.lastname: Tian
authors.forename: Si-Ming
authors.initials: SM
authors.lastname: Zhu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001772:Blood Cell Count; D001798:Blood Proteins / Q000378:metabolism; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D004573:Electrolytes / Q000097:blood; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D010843:Pichia / Q000201:enzymology / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000633:toxicity; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000633:toxicity*; D016482:Urinalysis; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D001798:Blood Proteins; D004573:Electrolytes; D006454:Hemoglobins; D011994:Recombinant Proteins; D003404:Creatinine; D013482:Superoxide Dismutase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin