A new antioxidant compound H-290/51 attenuates nitric oxide synthase and heme oxygenase expression following hyperthermic brain injury. An experimental study using immunohistochemistry in the rat.
Influence of a new anti-oxidant compound H-290/51 on expression of nitric oxide synthase (NOS) and heme oxygenase (HO) enzymes responsible for nitric oxide (NO) and carbon monoxide (CO) production, respectively was examined in the CNS following heat stress in relation to cell injury. Exposure of rats to 4h heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator (relative humidity 50-55%, wind velocity 20-25cm/sec) resulted in profound edema and cell injury in many parts of the cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus and brain stem. Immunostaining of constitutive isoforms of neuronal NOS (nNOS) and HO-2 revealed marked upregulation in damaged and distorted neurons located within the edematous brain regions. Pretreatment with H-290/51 (50 mg/kg, p.o., 30 min before heat stress) significantly reduced the edematous swelling and cell injury and resulted in a marked attenuation of nNOS and HO-2 expression. These observations suggest that upregulation of NOS and HO is associated with cell injury, and the antioxidant compound H-290/51 is neuroprotective in heat stress.
Alm
P
P
Department of Pathology, University Hospital, Lund, Sweden.
Sharma
H S
HS
Sjöquist
P O
PO
Westman
J
J
D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology*; D001812:Blood-Brain Barrier; D001930:Brain Injuries / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D005334:Fever / Q000201:enzymology*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007150:Immunohistochemistry; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D004791:Enzyme Inhibitors; C088233:H290-51; D007211:Indoles; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D006419:Heme Oxygenase (Decyclizing)