Therapeutic Treatment With L-Arginine Rescues Mice From Heat Stroke-Induced Death: Physiological and Molecular Mechanisms

Abstract

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.

Systemic Hyperthermia Induces Ischemic Brain Injury in Neonatal Mice With Ligated Carotid Artery and Jugular Vein

“…Heat stroke is characterized by the development of cerebral ischemic injury following severe heat exposure (30,31). The ambient temperature (38.5°C) used in this study was significantly lower compared with that used in heat-stroke models in rats (43°C) (32) and mice (41.8°C) (33). Nevertheless, the CAϩJV-ligated mice developed brain infarcts ipsilateral to the ligation side.…”

Transplantation of Human Dental Pulp-Derived Stem Cells Protects against Heatstroke in Mice

“…According to the findings of Chatterjee et al (5,6), WBH-treated mice were unable to maintain their normal thermoregulation. When they were exposed to room temperature (26°C), they displayed thermoregulatory deficits (e.g., hypothermia).…”

“…ICR male mice 8 to 10 weeks old were exposed to WBH (41.2°C, relative humidity 50-55%, for 1 h) in an environmental temperature-controlled chamber (5,6,9). The heated mice were returned to the normal room temperature (26°C) after the end of WBH.…”

Cyclooxygenase inhibitor induces the upregulation of connexin-43 expression in C6 glioma cells

“…Gliomas are characterized by an intense local invasiveness that limits the usefulness of preferred surgical treatment (2,3). Therefore, reducing the invasiveness of glioma will allow for a significant treatment option for brain tumors.…”