Hydrogen sulphide-induced hypothermia attenuates stress-related ulceration in rats.
1. Hydrogen sulphide (H(2)S) acts as a gaseous cellular messenger and has recently been reported to induce a suspended animation-like state in mice. The aim of the present study was to investigate the protective role of H(2)S exposure in stress gastric ulcer. 2. In the present study, we used a rat model of water immersion and restraint stress (WRS) to induce the typical stress disease, namely stress gastric ulcer. Rats were treated with WRS for 4 h, with or without pre-exposure to H(2)S (160 p.p.m. H(2)S for 2.5 h). 3. In H(2)S-exposed rats, body temperature was significantly reduced by 2.5C (P < 0.01) and oxygen consumption was reduced by 37.1% (P < 0.01) compared with control rats. Plasma levels of H(2)S were increased by 20.8% (P < 0.01) following pre-exposure. Pre-exposure to H(2)S significantly reduced the gastric ulcer index, from 24 +/- 9 to 9 +/- 2 (P < 0.01), in WRS rats. In addition, WRS increased plasma levels of adrenocorticotropin (ACTH) and corticosterone 4.7- and 4.8-fold, respectively (both P < 0.01). Pre-exposure to H(2)S markedly suppressed plasma ACTH and corticosterone level by 34.4 and 53.2%, respectively (both P < 0.01), and reduced WRS-elevated myeloperoxidase (MPO) activity by 19%. In the present study, WRS increased gastric malondialdehyde and conjugated diene content by 42 and 68%, respectively (both P < 0.01), and H(2)S exposure reduced lipid peroxide production. Finally, H(2)S exposure inhibited the WRS-elevated expression of glucose-regulated protein 78 and caspase 12, markers of endoplasmic reticulum stress. 4. In conclusion, a low concentration of H(2)S may be a new pharmacological tool for induced hypothermia to prevent severe stress-induced diseases and multifarious trauma in the clinical setting.
Lou
Li-Xia
LX
Institute of Cardiovascular Diseases, Peking University First Hospital, Beijing, China.
Geng
Bin
B
Du
Jun-Bao
JB
Tang
Chao-Shu
CS
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D053454:Caspase 12 / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology* / Q000627:therapeutic use; D007036:Hypothermia, Induced / Q000379:methods*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism / Q000473:pathology
D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D008315:Malondialdehyde; D000324:Adrenocorticotropic Hormone; D009195:Peroxidase; C506443:Casp12 protein, rat; D053454:Caspase 12; D003345:Corticosterone; D006862:Hydrogen Sulfide