title: L-Arginine reverses radiation-induced immune dysfunction: the need for optimum treatment window.
abstract: The aim of the present study was to investigate the protective efficacy of l-arginine in mitigating the injury induced by 2 Gy of total-body gamma radiation (TBI). Mice exposed to radiation (TBI group) had significantly decreased spleen weight, splenocyte numbers and bone marrow cellularity. Administration of l-arginine 2 h after TBI (TBI + l-arginine group) was effective in reducing the radiation-induced depletion of spleen and bone marrow cellularity but was not effective when administered before TBI (l-arginine + TBI group). The radiation-induced decrease in Con A-induced spleen cell proliferation, specific antibody response of spleen B cells to sheep red blood cells, and spleen RNA content was reversed in mice in the TBI + l-arginine group. The radiation-induced increase in serum TNF-alpha levels, serum nitrate/nitrite (NOx) levels, spleen DNA fragmentation, spleen nitric oxide synthase (NOS) activity, spleen inducible NOS (iNOS) activity, and hepatic iNOS activity was reversed in mice in the TBI + l-arginine group. l-Arginine administered before TBI could not reverse these changes. Mice in the TBI + l-arginine group had significantly increased spleen arginase activity compared to mice from either the TBI or l-arginine + TBI group. The results suggest the importance of the time of administration of l-arginine and the l-arginine pathway in mitigating the radiation-induced host immune dysfunction.
authors.affiliation: Immunology and Hyperthermia Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai - 400 085, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Shukla
authors.forename: Saurabh
authors.initials: S
authors.lastname: Chatterjee
authors.forename: V S
authors.initials: VS
authors.lastname: Thakur
authors.forename: Sudha
authors.initials: S
authors.lastname: Premachandran
authors.forename: Rahul
authors.initials: R
authors.lastname: Checker
authors.forename: T B
authors.initials: TB
authors.lastname: Poduval
mesh_terms: D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D017931:DNA Primers; D007154:Immune System Diseases / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha; D001120:Arginine; D052247:Nitric Oxide Synthase Type II