title: L-arginine mitigates radiation-induced early changes in cardiac dysfunction: the role of inflammatory pathways.
abstract: Our earlier studies demonstrated the ability of L-arginine (L-Arg) to reverse radiation-induced immune dysfunction. The aim of the present study was to investigate cardiac dysfunction up to 24 h after 2 Gy of total-body irradiation (TBI) and its mitigation by L-Arg. The current studies also explore the association of radiation-induced inflammation and electrocardiographic (ECG) abnormalities. TBI-induced cardiac iNOS and kinin B1 R, changes in the ECG profile like bradycardia, increased RR interval, ST elevation and increased QRS duration at 4 h and 24 h after TBI. TBI with 2 Gy induced inflammatory responses in spleen and cardiac tissue. L-Arg administered 2 h after TBI (TBI+L-Arg) mitigated the entire inflammatory response and ECG profile toward normalcy. L-Arg administered just before TBI (L-Arg +TBI) could not reverse the above-mentioned changes. Radiation-induced inflammatory responses at +4 h and +24 h after TBI in spleen and cardiac tissue correlated with the changes in ECG profile at the corresponding time. The results suggest the ability of L-Arg administered at the correct therapeutic window to mitigate radiation-induced cardiac dysfunction at 4 and 24 h after TBI.
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: Nazir M
authors.initials: NM
authors.lastname: Khan
authors.forename: Vikas S
authors.initials: VS
authors.lastname: Thakur
authors.forename: T Balakrishna
authors.initials: TB
authors.lastname: Poduval
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001919:Bradycardia / Q000188:drug therapy / Q000209:etiology; D016207:Cytokines / Q000378:metabolism; D004562:Electrocardiography; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology / Q000528:radiation effects*; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011837:Radiation-Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D043783:Receptor, Bradykinin B1 / Q000235:genetics; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D013997:Time Factors
chemical_list: D015415:Biomarkers; D016207:Cytokines; D011837:Radiation-Protective Agents; D043783:Receptor, Bradykinin B1; D001120:Arginine; D052247:Nitric Oxide Synthase Type II