Therapeutic treatment with L-arginine rescues mice from heat stroke-induced death: physiological and molecular mechanisms.
Heat stroke-induced death is a major killer worldwide. Mice were subjected to acute heat stress by exposing them to whole-body hyperthermia (WBH) treatment and were used as a model to study heat stroke. Administration of L-arginine (L-arg, 120 mg/kg, i.p) 2 h after the cessation of WBH rescued the mice from heat-induced death and reduced the hypothermia. Heat shock protein 70 levels in the liver were increased significantly in heat-stressed mice administered L-arg compared with the heat-stressed group. WBH induced apoptosis, as indicated by DNA fragmentation, and increased levels of p53 and caspase-3 activity, which were significantly reduced by the administration of L-arg. The levels of inducible nitric oxide synthase in the liver, nitrite, and inflammatory cytokines like interleukin 1beta and tumor necrosis factor-alpha in the serum increased in WBH-treated mice. The levels of the above markers of heat stress significantly decreased in L-arg-treated mice. Kinin-B1 receptor (kinin-B1R) in cardiac tissue that is upregulated in heat stressed mice was significantly lower in L-arg-administered mice. These data suggest the potential use of L-arg, a nonessential amino acid that is used as an enteral diet supplement, to treat heat stroke-related injury when administered at the appropriate dose and time.
Chatterjee
Saurabh
S
Immunology and Hyperthermia Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai-400 085, India.
Premachandran
Sudha
S
Sharma
Deepak
D
Bagewadikar
Raghavendra S
RS
Poduval
T B
TB
D000601:Amino Acids, Essential / Q000737:chemistry; D000818:Animals; D017209:Apoptosis; D001120:Arginine / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006321:Heart / Q000502:physiology; D018883:Heat Stroke; D006358:Hot Temperature; D006979:Hyperthermia, Induced / Q000379:methods*; D008099:Liver / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D043783:Receptor, Bradykinin B1 / Q000502:physiology* / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
D000601:Amino Acids, Essential; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D009573:Nitrites; D011506:Proteins; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D001120:Arginine; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases