title: Analysis of a metalloporphyrin antioxidant mimetic (MnTE-2-PyP) as a radiomitigator: prostate tumor and immune status.
abstract: Due to radiation-induced immune depression and development of pathologies such as cancer, there is increasing urgency to identify radiomitigators that are effective when administered after radiation exposure. The main goal of this study was to determine the radiomitigation capacity of MnTE-2-PyP[Mn(III) tetrakis (N-ethylpyridinium-2-yl) porphyrin], a superoxide dismutase (SOD) mimetic, and evaluate leukocyte parameters in spleen and blood. C57BL/6 mice were total-body exposed to 2 Gy γ-rays (Co-60), i.e., well below a lethal dose, followed by subcutaneous implantation of 5 × 10(5) RM-9 prostate tumor cells and initiation of MnTE-2-PyP treatment (day 0); interval between each procedure was 1-2 h. The drug was administered daily (12 times). Tumor progression was monitored and immunological analyses were performed on a subset per group on day 12. Animals treated with MnTE-2-PyP alone had significantly slower tumor growth compared to mice that did not receive the drug (P < 0.05), while radiation alone had no effect. Treatment of tumor-bearing mice with MnTE-2-PyP alone significantly increased spleen mass relative to body mass; the numbers of splenic white blood cells (WBC) and lymphocytes (B and T), as well as circulating WBC, granulocytes, and platelets, were high compared to one of more of the other groups (P < 0.05). The results show that MnTE-2-PyP slowed RM-9 tumor progression and up-regulated immune parameters, but mitigation of the effects of 2 Gy total-body irradiation were minimal.
authors.affiliation: Department of Basic Sciences, Divisions of Biochemistry and Microbiology, Loma Linda University and Medical Center, Loma Linda, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mehrotra
authors.forename: M J
authors.initials: MJ
authors.lastname: Pecaut
authors.forename: T L
authors.initials: TL
authors.lastname: Freeman
authors.forename: J D
authors.initials: JD
authors.lastname: Crapo
authors.forename: A
authors.initials: A
authors.lastname: Rizvi
authors.forename: X
authors.initials: X
authors.lastname: Luo-Owen
authors.forename: J M
authors.initials: JM
authors.lastname: Slater
authors.forename: D S
authors.initials: DS
authors.lastname: Gridley
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001772:Blood Cell Count; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry; D009929:Organ Size; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D013154:Spleen / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D013482:Superoxide Dismutase / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects; D014916:Whole-Body Irradiation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000975:Antioxidants; D008665:Metalloporphyrins; D011837:Radiation-Protective Agents; C520506:manganese tetrakis-(N-ethyl-2 pyridyl) porphyrin; D013482:Superoxide Dismutase