Protective effects of alpha-tocopherol and mannitol in both circulatory shock and cerebral ischaemia injury in rat heatstroke.
1. There is evidence that hydroxyl radicals are accumulated and oxidative stress is produced in multiple organs, including the brain, of rats with heat stroke. Herein, we investigated the effect on heat stroke-induced circulatory shock and cerebral ischaemic injury of two free radical scavengers, namely mannitol and alpha-tocopherol. 2. Urethane-anaesthetized rats were exposed to heat stress (ambient temperature 42 degrees C) to induce heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure and cerebral blood flow after the onset of heat stroke were significantly lower in heat stroke rats than in control rats. However, cerebral free radicals, lipid peroxidation and the neuronal damage score were greater in heat stroke rats compared with control rats. Similarly, plasma cytokines, including tumour necrosis factor-alpha, interleukin (IL)-1beta and IL-6, were significantly higher in heat stroke rats compared with their normothermic controls. 3. Pretreatment with alpha-tocopherol (20 mg/kg, i.v.) or mannitol (10%, i.v.) 30 min before the onset of heat exposure significantly attenuated heat stroke-induced arterial hypotension, cerebral ischaemia and neuronal damage, the increased free radical formation and lipid peroxidation in the brain and the increased plasma levels of cytokines. Pretreatment with alpha-tocopherol or mannitol resulted in a prolongation of survival time in heat stroke. 4. These results demonstrate that although pretreatment with alpha-tocopherol and mannitol does not prevent the heat stroke syndrome entirely, an attenuation of the syndrome is observed.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018883:Heat Stroke / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017665:Hydroxyl Radical / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008353:Mannitol / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D024502:alpha-Tocopherol / Q000494:pharmacology / Q000627:therapeutic use*
D017665:Hydroxyl Radical; D008353:Mannitol; D024502:alpha-Tocopherol