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Dexamethasone improves heat stroke-induced multiorgan dysfunction and damage in rats.

Liu CC, Shih MF, Wen YS, Lai YH, Yang TH - Int J Mol Sci (2014)

Bottom Line: The results indicated that all the rats suffering from heat stroke showed high serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), accompanied with increased prothrombin time, activated partial thromboplastin time and D-D dimer, and decreased protein C.High striatal levels of glycerol, glutamate, and lactate/pyruvate were simultaneously detected.On the contrary, the mean arterial pressure, plasma levels of interleukin-10 (IL-10), and local cerebral blood flow at the striatum were all decreased.

View Article: PubMed Central - PubMed

Affiliation: Department and Institute of Cosmetic Science, Chia-Nan University of Pharmacy and Science, Tainan 717, Taiwan. ccliu@mail.cnu.edu.tw.

ABSTRACT
Dexamethasone (DXM) is known as an immunosuppressive drug used for inflammation control. In the present study, we attempted to examine whether DXM administration could attenuate the hypercoagulable state and the overproduction of pro-inflammatory cytokines, improve arterial hypotension, cerebral ischemia and damage, and vital organ failure in a rat model of heat stroke. The results indicated that all the rats suffering from heat stroke showed high serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), accompanied with increased prothrombin time, activated partial thromboplastin time and D-D dimer, and decreased protein C. During the induction period of heat stroke, plasma levels of blood urea nitrogen (BUN), creatinine, glutamic oxaloacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT), and alkaline phosphatase (ALP), were consistently increased. High striatal levels of glycerol, glutamate, and lactate/pyruvate were simultaneously detected. On the contrary, the mean arterial pressure, plasma levels of interleukin-10 (IL-10), and local cerebral blood flow at the striatum were all decreased. Importantly, intravenous administration of DXM substantially ameliorated the circulatory dysfunction, systematic inflammation, hypercoagulable state, cerebral ischemia and damage during the induction period of heat stroke. These findings demonstrated that DXM may be an alternative therapy that can ameliorate heat stroke victims by attenuating activated coagulation, systemic inflammation, and vital organ ischemia/injury during heat stroke.

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Effects of heat exposure (43 °C) on plasma levels of prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen degradation products (FDP), D-D dimer, and protein C in normothermic control rats (white bar), saline-treated (black bar) or dexamethasone-treated rats (grey bar, 8 mk/kg b.w., i.v.). *p < 0.05, in comparison with normothermic control rats; †p < 0.05, in comparison with saline-treated rats (ANOVA followed by Duncan’s test). The values were obtained 85 min after the initiation of heat exposure (or 15 min after the onset of heat stroke) in heat stroke rats or the equivalent time in normothermic controls. Bars are each the mean ± S.E. of 8 rats for each groups.
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ijms-15-21299-f002: Effects of heat exposure (43 °C) on plasma levels of prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen degradation products (FDP), D-D dimer, and protein C in normothermic control rats (white bar), saline-treated (black bar) or dexamethasone-treated rats (grey bar, 8 mk/kg b.w., i.v.). *p < 0.05, in comparison with normothermic control rats; †p < 0.05, in comparison with saline-treated rats (ANOVA followed by Duncan’s test). The values were obtained 85 min after the initiation of heat exposure (or 15 min after the onset of heat stroke) in heat stroke rats or the equivalent time in normothermic controls. Bars are each the mean ± S.E. of 8 rats for each groups.

Mentions: Figure 2 summarizes the plasma levels of prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen degradation products (FDP), protein C, and D-D dimer for normothermic controls, normal saline-treated heat stroke rats, and DXM-treated heat stroke rats. It can be seen from Figure 2 that PT, aPTT, FDP, and D-D dimer values during heat stroke for rats treated with normal saline (1 mL/kg b.w., i.v.) are all significantly higher at 85 min after the start of heat exposure than those of the normothermic controls. On the contrary, the value for plasma of protein C is significantly lower than that of the normothermic controls. In turn, administration with DXM (8 mg/mL b.w., i.v.) at 70 min after initiation of heat exposure (or immediately at the onset of heat stroke) appreciably attenuates the heat stress-induced increased plasma levels of PT, aPTT, FDP, and D-D dimer as well as the decreased plasma levels of protein C.


Dexamethasone improves heat stroke-induced multiorgan dysfunction and damage in rats.

Liu CC, Shih MF, Wen YS, Lai YH, Yang TH - Int J Mol Sci (2014)

Effects of heat exposure (43 °C) on plasma levels of prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen degradation products (FDP), D-D dimer, and protein C in normothermic control rats (white bar), saline-treated (black bar) or dexamethasone-treated rats (grey bar, 8 mk/kg b.w., i.v.). *p < 0.05, in comparison with normothermic control rats; †p < 0.05, in comparison with saline-treated rats (ANOVA followed by Duncan’s test). The values were obtained 85 min after the initiation of heat exposure (or 15 min after the onset of heat stroke) in heat stroke rats or the equivalent time in normothermic controls. Bars are each the mean ± S.E. of 8 rats for each groups.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264226&req=5

ijms-15-21299-f002: Effects of heat exposure (43 °C) on plasma levels of prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen degradation products (FDP), D-D dimer, and protein C in normothermic control rats (white bar), saline-treated (black bar) or dexamethasone-treated rats (grey bar, 8 mk/kg b.w., i.v.). *p < 0.05, in comparison with normothermic control rats; †p < 0.05, in comparison with saline-treated rats (ANOVA followed by Duncan’s test). The values were obtained 85 min after the initiation of heat exposure (or 15 min after the onset of heat stroke) in heat stroke rats or the equivalent time in normothermic controls. Bars are each the mean ± S.E. of 8 rats for each groups.
Mentions: Figure 2 summarizes the plasma levels of prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen degradation products (FDP), protein C, and D-D dimer for normothermic controls, normal saline-treated heat stroke rats, and DXM-treated heat stroke rats. It can be seen from Figure 2 that PT, aPTT, FDP, and D-D dimer values during heat stroke for rats treated with normal saline (1 mL/kg b.w., i.v.) are all significantly higher at 85 min after the start of heat exposure than those of the normothermic controls. On the contrary, the value for plasma of protein C is significantly lower than that of the normothermic controls. In turn, administration with DXM (8 mg/mL b.w., i.v.) at 70 min after initiation of heat exposure (or immediately at the onset of heat stroke) appreciably attenuates the heat stress-induced increased plasma levels of PT, aPTT, FDP, and D-D dimer as well as the decreased plasma levels of protein C.

Bottom Line: The results indicated that all the rats suffering from heat stroke showed high serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), accompanied with increased prothrombin time, activated partial thromboplastin time and D-D dimer, and decreased protein C.High striatal levels of glycerol, glutamate, and lactate/pyruvate were simultaneously detected.On the contrary, the mean arterial pressure, plasma levels of interleukin-10 (IL-10), and local cerebral blood flow at the striatum were all decreased.

View Article: PubMed Central - PubMed

Affiliation: Department and Institute of Cosmetic Science, Chia-Nan University of Pharmacy and Science, Tainan 717, Taiwan. ccliu@mail.cnu.edu.tw.

ABSTRACT
Dexamethasone (DXM) is known as an immunosuppressive drug used for inflammation control. In the present study, we attempted to examine whether DXM administration could attenuate the hypercoagulable state and the overproduction of pro-inflammatory cytokines, improve arterial hypotension, cerebral ischemia and damage, and vital organ failure in a rat model of heat stroke. The results indicated that all the rats suffering from heat stroke showed high serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), accompanied with increased prothrombin time, activated partial thromboplastin time and D-D dimer, and decreased protein C. During the induction period of heat stroke, plasma levels of blood urea nitrogen (BUN), creatinine, glutamic oxaloacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT), and alkaline phosphatase (ALP), were consistently increased. High striatal levels of glycerol, glutamate, and lactate/pyruvate were simultaneously detected. On the contrary, the mean arterial pressure, plasma levels of interleukin-10 (IL-10), and local cerebral blood flow at the striatum were all decreased. Importantly, intravenous administration of DXM substantially ameliorated the circulatory dysfunction, systematic inflammation, hypercoagulable state, cerebral ischemia and damage during the induction period of heat stroke. These findings demonstrated that DXM may be an alternative therapy that can ameliorate heat stroke victims by attenuating activated coagulation, systemic inflammation, and vital organ ischemia/injury during heat stroke.

Show MeSH
Related in: MedlinePlus