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.

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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.

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