Effects of hemin on heat stress-induced renal injury in rats
碩士 === 國防醫學院 === 生理學研究所 === 96 === Heat stroke is a serious life-threatening disease characterized by hyperthermia (body temperature >40.5°C), central nervous system abnor- malities and multi-organ dysfunction. Despite through adequate lowering body temperature and aggressive treatment, the progr...
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ndltd-TW-096NDMC01160082016-05-16T04:09:53Z http://ndltd.ncl.edu.tw/handle/15069194186951659418 Effects of hemin on heat stress-induced renal injury in rats 探討Hemin對熱傷害所誘發腎臟損傷之影響 Yi-chia Huang 黃怡嘉 碩士 國防醫學院 生理學研究所 96 Heat stroke is a serious life-threatening disease characterized by hyperthermia (body temperature >40.5°C), central nervous system abnor- malities and multi-organ dysfunction. Despite through adequate lowering body temperature and aggressive treatment, the progression of this disease is still unsatisfactorily. The morbidity of acute renal failure occurred in patients with heat stroke is about 50%. Heme oxygenase-1 (HO-1) is a key enzyme accounting for the heme degradation, producing iron, carbon monoxide (CO), and biliverdin which is rapidly converted to bilirubin. The protective effects of HO-1 were related to the biological actions of bilirubin, a potent antioxidant, and CO have vasodilation and anti-inflammation by enhancing guanylyl cyclase activity and c-GMP formation. It has been demonstrated that induction of HO-1 possesses a cytoprotective effect in various types of renal injury. However, whether treatment with hemin, a HO-1 inducer, has a protective activity in heat stress-induced renal injury is still unknown. In this study, we first evaluated the effect of hemin on heat stress-induced renal injury in rats, and further investigated the possible mechanisms involved. The heat stress model was established by putting the male Sprague-Dawley (SD) rats into a chamber at 40°C for 1 hour. Our results showed that pre-treatment with hemin (30 mg/kg, i.p.) at 24 hour before heat stress significantly inhibited the heat stress-induced hyperthermia, hypotension, decreased renal blood flow, increase of serum levels of creatinine and expression of neutrophil gelatinase-associated lipocalin (NGAL) mRNA in renal tissue, accompanied by significant improvement of the pathological changes of renal tissue. In addition, increase of HO-1 expression by hemin also significantly reduced heat stress-induced increase of malondialdehyde, nitric oxide (NO) formation, pro-inflammatory cytokines including interleukin-1 and interleukin-6, and expression of cyclooxygenase-2 (COX-2) mRNA in the kidney. Importantly, the survival rate of heat-treated rats was also markedly increased by hemin from 30% to 70%. However, combined treatment with SnPP, a HO-1 inhibitor, the protective effects of hemin was strongly attenuated. In conclusion, we demonstrated that hemin has a protective effect in heat stress-induced renal injury, which may be associated with the activation of HO-1-mediated pathways and inhibition of pro-inflammatory mediators formation. Tz-Chong Chou 周志中 2008 學位論文 ; thesis 89 zh-TW |
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碩士 === 國防醫學院 === 生理學研究所 === 96 === Heat stroke is a serious life-threatening disease characterized by hyperthermia (body temperature >40.5°C), central nervous system abnor- malities and multi-organ dysfunction. Despite through adequate lowering body temperature and aggressive treatment, the progression of this disease is still unsatisfactorily. The morbidity of acute renal failure occurred in patients with heat stroke is about 50%. Heme oxygenase-1 (HO-1) is a key enzyme accounting for the heme degradation, producing iron, carbon monoxide (CO), and biliverdin which is rapidly converted to bilirubin. The protective effects of HO-1 were related to the biological actions of bilirubin, a potent antioxidant, and CO have vasodilation and anti-inflammation by enhancing guanylyl cyclase activity and c-GMP formation. It has been demonstrated that induction of HO-1 possesses a cytoprotective effect in various types of renal injury. However, whether treatment with hemin, a HO-1 inducer, has a protective activity in heat stress-induced renal injury is still unknown. In this study, we first evaluated the effect of hemin on heat stress-induced renal injury in rats, and further investigated the possible mechanisms involved. The heat stress model was established by putting the male Sprague-Dawley (SD) rats into a chamber at 40°C for 1 hour. Our results showed that pre-treatment with hemin (30 mg/kg, i.p.) at 24 hour before heat stress significantly inhibited the heat stress-induced hyperthermia, hypotension, decreased renal blood flow, increase of serum levels of creatinine and expression of neutrophil gelatinase-associated lipocalin (NGAL) mRNA in renal tissue, accompanied by significant improvement of the pathological changes of renal tissue. In addition, increase of HO-1 expression by hemin also significantly reduced heat stress-induced increase of malondialdehyde, nitric oxide (NO) formation, pro-inflammatory cytokines including interleukin-1 and interleukin-6, and expression of cyclooxygenase-2 (COX-2) mRNA in the kidney. Importantly, the survival rate of heat-treated rats was also markedly increased by hemin from 30% to 70%. However, combined treatment with SnPP, a HO-1 inhibitor, the protective effects of hemin was strongly attenuated. In conclusion, we demonstrated that hemin has a protective effect in heat stress-induced renal injury, which may be associated with the activation of HO-1-mediated pathways and inhibition of pro-inflammatory mediators formation.
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author2 |
Tz-Chong Chou |
author_facet |
Tz-Chong Chou Yi-chia Huang 黃怡嘉 |
author |
Yi-chia Huang 黃怡嘉 |
spellingShingle |
Yi-chia Huang 黃怡嘉 Effects of hemin on heat stress-induced renal injury in rats |
author_sort |
Yi-chia Huang |
title |
Effects of hemin on heat stress-induced renal injury in rats |
title_short |
Effects of hemin on heat stress-induced renal injury in rats |
title_full |
Effects of hemin on heat stress-induced renal injury in rats |
title_fullStr |
Effects of hemin on heat stress-induced renal injury in rats |
title_full_unstemmed |
Effects of hemin on heat stress-induced renal injury in rats |
title_sort |
effects of hemin on heat stress-induced renal injury in rats |
publishDate |
2008 |
url |
http://ndltd.ncl.edu.tw/handle/15069194186951659418 |
work_keys_str_mv |
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