Curcumin alleviates acute kidney injury in a dry-heat environment by reducing oxidative stress and inflammation in a rat model.

Curcumin exhibits anti-inflammatory and antioxidant activities. We investigated the protective effects of curcumin in a renal injury rat model under dry-heat conditions. We divided Sprague-Dawley rats into four groups: dry-heat 0- (normal temperature control group), 50-, 100-, and 150-minute groups. Each group was divided into five subgroups (n = 10): normal saline (NS), sodium carboxymethylcellulose (CMCNa), and curcumin pretreated low, medium, and high-dose (50, 100, and 200 mg/kg, respectively) groups. Compared to the normal temperature group, serum creatinine, blood urea nitrogen, urinary kidney injury molecule-1, and neutrophil gelatinase-associated load changes in lipoprotein (NGAL) levels were significantly increased in the dry-heat environment group (P < .05); inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and malondialdehyde (MDA) and related inflammatory factor levels were increased in the kidney tissue. Superoxide dismutase (SOD) and catalase (CAT) levels were decreased. However, following all curcumin pretreatment, the serum levels of kidney injury indicators and NGAL were decreased in the urine compared to those in the NS and CMCNa groups (P < .05), whereas renal SOD and CAT activities were increased and MDA was decreased (P < .05). Renal tissues of the 150-minute group showed obvious pathological changes. Compared to the NS group, pathological changes in the renal tissues of the 100- and 200-mg/kg curcumin groups were significantly reduced. Furthermore, iNOS and COX-2 expression and inflammatory factor levels were decreased after curcumin treatment. Curcumin exerted renoprotective effects that were likely mediated by its antioxidant and anti-inflammatory effects in a dry-heat environment rat model.

Effect of curcumin on expressions of CD11b and CD19 in peripheral blood of heat stroke rats in a simulation dry-heat environment / 中华危重病急救医学

Objective? To?investigate?the?effects?of?different?doses?of?curcumin?on?the?levels?of?immune?factors?CD11b?and?CD19?in?peripheral?blood?of?heat?stroke?rats?in?a?simulation?dry-heat?environment.? Methods? 160?SPF??healthy?male?Sprague-Dawley?(SD)?rats?were?selected?and?divided?into?different?groups?according?to?random?number?table?method:?normal?saline?(NS)?control?group?(given?NS),?solvent?control?group?[given?sodium?carboxymethylcellulose?(CMCNa)],?and?curcumin?low,?medium?and?high?dose?pretreatment?group?(given?0.05,?0.10,?0.20?mg/g?of?curcumin+0.5%?CMCNa?solution).?There?were?32?rats?in?each?group,?and?were?challenged?only?by?10?mL·kg-1·d-1?lavage,?and?continuous?dosing?for?7?days.?On?the?8th?day,?rats?were?challenged?at?ambient?temperature?(41.0±0.5)?℃,?relative?humidity?(10±1)%?of?the?northwest?in?the?special?environment?of?artificial?lab,?placed?in?0?(normal?temperature),?50,?100?and??150?minutes?respectively.?The?levels?of?CD19?and?CD11b?in?peripheral?blood?of?each?rat?were?detected?by?flow?cytometry?instrument.? Results? With?the?extension?of?time?in?the?simulated?dry?and?heat?environment,?the?level?of?CD11b?in?peripheral?blood?was?gradually?increased?in?each?group,?and?the?peak?value?was?reached?at?150?minutes,?the?NS?control?group,?solvent?control?group?and?curcumin?low,?medium?and?high?dose?pretreatment?groups?were?0.346±0.013,?0.342±0.013,?0.342±0.012,?0.325±0.012,?and?0.281±0.012,?respectively.?In?each?group,?the?level?of?CD19?was? first?increased?and?then?decreased,?reaching?its?peak?value?at?100?minutes,?and?the?level?of?the?NS?control?group,?solvent?control?group?and?curcumin?low,?medium?and?high?dose?pretreatment?groups?were?0.586±0.010,?0.601±0.014,?0.684±0.009,?0.613±0.012?and?0.604±0.006,?respectively.?The?level?of?CD11b?in?the?curcumin?medium?and?high?dose?pretreatment?groups?were?significantly?lower?than?those?in?the?NS?control?group?and?solvent?control?group??(50?minutes:?0.237±0.011,?0.188±0.006?vs.?0.283±0.009,?0.289±0.012;?100?minutes:?0.260±0.010,?0.248±0.008?vs.?0.293±0.008,?0.290±0.007,?all?P?<?0.05),?and?after?placement?for?150?minutes,?the?level?of?CD11b?in?the?curcumin?high?dose?pretreatment?group?was?significantly?lower?than?that?in?the?NS?control?group,?solvent?control?group?and?curcumin?low?dose?pretreatment?group?(0.281±0.012?vs.?0.346±0.013,?0.342±0.013,?0.342±0.012,?all?P?<?0.05).?The?level?of?CD19?in?the?curcumin?low,?medium?and?high?dose?pretreatment?groups?were?significantly?higher?than?those?in?the?NS?control?group?and?solvent?control?group?at?50?minutes?in?the?dry?and?hot?environment?(0.394±0.001,?0.436±0.009,?0.553±0.011?vs.?0.205±0.005,?0.197±0.003,?all?P?<?0.05),?at?100?minutes,?the?level?of?CD19?in?the?curcumin?low?dose?pretreatment?group?was?significantly?higher?than?that?in?the?NS?control?group?and?solvent?control?group?(0.684±0.009?vs.?0.586±0.010,?0.601±0.014,?both?P?<?0.05),?there?was?no?significant?difference?in?CD19?level?between?the?other?dose?pretreatment?groups?and?NS?control?group;?at?150?minutes,?there?was?no?significant?difference?in?CD19?level?between?the?curcumin?pretreatment?groups,?the?NS?control?group,?and?the?solvent?control?group.?The?peripheral?blood?immune?factors?CD11b?and?CD19?levels?in?the?NS?control?group?and?solvent?control?group?were?not?significantly?changed,?and?there?was?no?significant?difference?between?two?groups.? Conclusion? Curcumin?pretreatment?can?reduce?the?level?of?CD11b?and?increase?the?level?of?CD19?in?peripheral?blood?of?rats?with?dry?heat?stroke?in?the?early?and?middle?stages,?which?may?enhance?the?heat?resistance?and?prevent?the?occurrence?of?multiple?organ?dysfunction?by?increasing?the?body?immunity,?and?this?effect?has?nothing?to?do?with?the?dose?of?curcumin.

Effect of different concentrations of curcumin on inflammatory factors and endotoxin changes in lung tissues of rats with heatstroke in dry-heat environment / 医学研究生学报

Objective Thermal injury causes pulmonary edema, which may lead to acute respiratory distress syndrome, sepsis, multiorgan failure and even death. The article aimed to study the mechanism of curcumin pretreatment on inflammatory factors in lung tissues and serum endotoxin of rats with dry-heat environment.Methods A total of 50 SD rats were randomly divided into 5 groups (n=10): normal control group, dry heat control group, low concentraion group (50mg/kg curcumin pretreatment group), middle concentraion group (100mg/kg curcumin pretreatment group), and high concentration group (200mg/kg curcumin pretreatment group). Rats in normal control group and dry heat control group were given normal saline by gavage, while rats in 3 curcumin pretreatment groups were given curcumin of different concentrations (50 mg/kg, 100 mg/kg, 200 mg/kg) by gavage once a day for 7 consecutive days. At 8d, all the other 4 groups except normal control group were transferred to the climate cabin (The Simulated Climate Cabin for Special Environment of Northwest of China) with the condition of (41±0.5)℃, (10±1)% relative humidity.The rats were put in the dry-heat environment for 150min, then they were anaesthetized and sacrificed at 150min to collect the blood, lung tissues for further analysis. Observation was made on the pathological changes of lung tissues of rats in each group and the changes of inflammatory factors such as IL-1β, IL-6, TNF-α and LPS.Results Compared with dry heat control group, the concentrations of IL-1β, IL-6, TNF-α and LPS in normal control group, curcumin pretreatment groups with low concentration, middle concentration and high concentration were significantly higher(P<0.01). The concentrations of IL-1β, IL-6, TNF-α and LPS in curcumin pretreatment group with low concentration were significantly lower than those curcumin pretreatment groups with middle concentration and high concentration(P<0.05). Compared with curcumin pretreatment group with middle concentration, LPS concentration of curcumin pretreatment group with high concentration decreased significantly (P<0.01). Pearson correlation analysis showed that there was a positive correlation between the plasma of LPS and inflammatory cytokines of IL-1β, IL-6, and TNF-α in lung tissues (correlation coefficient r=0.866, r=0.900, r=0.885, P=0.000).Conclusion Curcumin inhibits bacterial endotoxin in blood, reduces the expression of inflammatory factors, and plays an important role in alleviating secondary multiple organ damage, which means curcumin pretreatment can relieve lung damage caused by heatstroke and reduce the mortality of heatstroke.

The features of serum K+variation in swine with traumatic hemorrhagic shock within the dry-heat environment / 中华急诊医学杂志

Objective To observe the changes of potassium ion (K+), lactic acid (Lac) and glucose (Glu) in swine with traumatic hemorrhagic shock (THS) inside the dry-heat environment and to explore its possible mechanism. Methods A total of 40 local Landrace piglets were randomly(random number) divided equally into 4 groups: the normal temperature sham operation group (NS), the normal temperature traumatic hemorrhagic shock group (NTHS), the dry-heat sham operation group (DS group) and the dry-heat traumatic hemorrhagic shock group (DTHS). The experiment was carried out in the artifi cia climate cabin simulated the special environment of northwest of China. After exposed to their respective environment[dry-heat environment: (40.5±0.5), plus(10±2)% humidity; normal temperature environment: (25±0.5), plus(35±5)% humidity] for 3 h. Laparotomy were performed in swine of all groups, and then splenectomy and partial hepatectomy were performed only in NTHS and DTHS. The process of exsanguination from the external iliac artery was established to make the MAP reaching to 40-50 mmHg, and thus the traumatic hemorrhagic shock model of swine was successfully made. Blood samples were collected from external iliac artery at different intervals including the time just after exposure for 3 h and the successful establishment of traumatic hemorrhagic shock model (0 h) and then every 30 min after 0 h, serum levels of K+, Lac and Glu were detected. The features of varied serum K+, Lac and Glu were observed in each group. All data were statistically analyzed using One-way ANOVA and Pearson correlation analysis. Results After exposed , the level of serum K+inside the dry-heat environment was higher than that of swine inside the normal temperature group ( P<0.01), however the Glu level was lower in the swine inside dry-heat environment than that of swine inside the normal temperature ( P<0.01).The level of serum K+and Lac of DTHS group were rapidly increased from the establishment of the model to the death in about 3 h, while those of NTHS group were increased slowly. The level of K+and Lac were positively correlated in the two groups amd the correlation coeffi cient were rDTHS=0.927 (P<0.01) and rNTHS=0.539 (P<0.01),respectively. The level of Glu was progressively decrease in DTHS group, while in NTHS group, it was not noticeable. The level of K+and Glu were negatively correlated in the two group, the correlation coeffi cient were rDTHS=-0.804 (P<0.01) and rNTHS=0.420 (P<0.01),respectively. Conclusions The changes of serum K+, Lac and Glu occurred sooner and more obvious in traumatic hemorrhagic shock models inside dry heat environment (DTHS) group than those in NTHS group. The level of serum K+positively correlated with Lac, however, negatively correlated with Glu, which suggested that hyperkalemia and acidosis should be paid more attention to the treatment of traumatic hemorrhagic shock inside the dry heat environment, and the hypoglycemia should be treated at the same time.

The changes of oxidative stress and caspase-3 in swine with traumatic hemorrhagic shock in dry-heat environment of desert / 中华急诊医学杂志

Objective To study the changes of oxidative stress and caspase-3 in swine with traumatic hemorrhagic shock in dry-heat environment of desert.Methods A total of 48 Landrace small swine were randomly(random number)divided into 2 groups(n=24 in each group), and then the traumatic hemorrhagic shock was established in room temperature environment and in dry-heat environmentin swine.Dry-heat environment traumatic hemorrhagic shock group (DHS), which was made in an artificial experiment cabin mimic the reality included swine exposed in the dry-heat environment of desert for 3 h (T0, n=6), T1 (50 min after shock modeling, n=6), T2 (100 min after shock modeling, n=6), T3 (150 min after shock modeling, n=6).At each interval, blood sample was collected to detect urea nitrogen (BUN) and creatinine, urine sample was collected to detect neutrophil gelatinase-associated lipoprotein (NGAL), kidney tissue samples were collected to evaluate renal morphological and tubular scores, as well as to detect catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA).Western blot was used to detect the level of caspase-3.Traumatic hemorrhagic shock group of room temperature environment (RTS) was established and variety of assays were carried out as same as those deteced in the dry-heat environment group.Results Compared with the room temperature environment exposed group,kidney damage index, antioxidant and caspase-3 were increased in desert dry-heat environment exposed for 3 h group, but there were no statistically significant difference(P> 0.05).And from T1 then on, the levels of NGAL, CAT and SOD in DHS groups were increased which were significant different from those in RTS group (P<0.05 or P<0.01).There were significant differences in BUN and creatinine at T2 between two groups(P<0.05).At T3, caspase-3 protein content in DHS group was significantly different from that in RTS group (P<0.01).Correlation analysis showed that the NGAL level was correlated with the levels to MDA (rRTS=0.935, rDHS =0.858, P<0.01) in RTS group and DHS group.Compared with RTS group, renal tissue under light microscope showed that Bowman appeared dilated with degeneration and exfoliated epithelial cells, proximal tubule epithelial shedding, and interstitial edema in DHS group.Electron microscope showed that mitochondria became pleomorphic, endoplasmic reticulum with fold broadening.Conclusions When traumatic hemorrhagic shock happened in the desert dry-heat environment, desert dry-heat environment can aggravate kidney damage, possibly by reducing the renal tissue antioxidant enzyme content and increase renal tissue caspase-3 activity to promote renal tissue apoptosis.Antioxidant stress and apoptosis may be an important role in the prevention of the secondary kidney injury induced by traumatic hemorrhagic shock in dry-heat environment.

The studies on the changes of nitric oxide synthase in the lung tissue of traumatic hemorrhagic shock rats under dry heat environment of desert and their relations to the secondary lung injuris / 中华急诊医学杂志

Objective To study the pathological changes and expressions of NO and iNOS mRNA in the lung tissue of traumatic hemorrhagic shock rats under dry heat environment of desert and their relations to the lung injury.Methods A total of 140 male SD rats were randomly (random number) ivided into the room temperature (25 ℃) environment traumatic hemorrhagic shock group (room temperature group) and the dry heat traumatic hemorrhagic shock groups (dry heat group,temperature 40℃,humidity 10％),respectively,and each groups was further randomly divided into 7 subgroups:the control subgroup,post shock subgroups at 0,0.5,1,1.5,2and 3 h (n =10 in each subgroup).The rats of control subgroup were not treated,and rats of dry heat group were placed in dry heat environment for 60 min,then anesthetized,fixed,and insertion of intravenous indwelling needles and catherization of right carotid artery,jugular vein and the right femoral artery were performed.After stabilization for 10 min,2500 g iron wheel was used to be dropped from 30 m height and vertically hit the upper left femoral of SD rats in order to make comminuted fracture,wounds were quickly dressed after injury.Exsanguination from right femoral artery was kept until MAP maintained at (35 ± 5) mmHg,and resuscitation was carried out after continue monitoring for 60 min.After the establishment of traumatic hemorrhagic shock model in each environment,the rats were sacrificed at given intervals,and thoracotomy was performed to take broncho-alveolar lavage fluid (BALF) and lung tissue.Pathological changes of lung tissues were observed by using HE staining and NO concentration of lung tissue was detected by one-step method,and changes of the iNOS mRNA expressions were detected by using fluorescence quantitative PCR.Then t test,ANOVA and Pearson correlation analysis were used for the data analysis.Results The pathological change in dry heat group at each interval was more severe,and pulmonary histopathological injury score was higher,and the protein exudation was more profuse compared with the room temperature group.NO concentration in lung tissue homogenate of dry heat group was higher than that of room temperature group (t =2.472,P ＜ 0.05),and the difference in NO level between different intervals within the dry heat group was statistically significant (F =6.77,P ＜ 0.01).The NO concentration in dry heat group reached its maximum at 2 h (3.35 ± 0.23) μmol / g and the peak value emerged sooner than that in room temperature group.The difference was statistically significant in overall expression of iNOS mRNA between two groups analyzed with t test (t =3.619,P ＜ 0.01),and there was statistically significant difference between intervals within the dry heat group (F =12.34,P ＜0.01).The values of iNOS mRNA in the dry heat group were higher than those in the room temperature group at the same given intervals,and the peak value appears at 1.5 h in dry heat group,and the room temperature group it began to increase at 2 h.The concentration of NO and the expression of iNOS mRNA were positively correlated with each other in two groups (r =0.680,r =0.376).The expression of iNOS mRNA and lung histopathological injury score was positively correlated in two groups (r =0.846,r =0.899).Conclusions When traumatic hemorrhagic shock occurred in the dry heat desert environment,the lung injury was more severe and appeared sooner than that in the room temperature environment.NO and iNOS played important roles in the secondary lung injury in the wake of traumatic hemorrhagic shock in rats under the dry heat environmengt of desert.

Changes in blood gas parameters of heatstroke rats in dry-heat environment of desert / 中华危重病急救医学

ObjectiveTo investigate the changes in characteristics of blood gas analysis of heatstroke rats residing in dry-heat environment of desert, and to provide a theoretical reference for its treatment in clinic.Methods Forty-eight male Sprague-Dawley (SD) adult rats under anesthesia were divided into six groups by random number table, with 8 rats in each group: namely mild, moderate, severe heatstroke groups and their corresponding control groups. The rats were placed in an artificial chamber with simulated desert dry-heat environment (temperature 41℃, humidity 10%) for about 70, 110, 145 minutes, respectively, to reproduce mild, moderate, severe heatstroke models. The rats in control groups were placed in a normothermic environment for corresponding duration. Abdominal aorta blood of each group was collected for blood gas analysis, and electrolytes were determined by a portable blood gas analyzer.Results① Arterial partial pressure of carbon dioxide (PaCO2) in mild heatstroke group was increased to (45.64±8.19) mmHg (1 mmHg = 0.133 kPa), arterial oxygen saturation (SaO2) was decreased to 0.84±0.08, pH value was lowered to 7.36±0.11, showing that respiratory acid-base imbalance was resulted. Base excess of extracellular fluid (BEecf) in moderate heatstroke group was decreased to (-3.00±0.76) mmol/L, HCO3- was decreased to (19.39±1.89) mmol/L, and pH value was lowered to 7.21±0.07, indicating that metabolic acid-base imbalance was aggravated gradually. The changes in parameters in severe heatstroke group gradually became more serious, and a significant difference was found as compared with those of mild and moderate heatstroke groups (PaCO2:F = 6.537,P = 0.006; SaO2:F = 5.174,P = 0.015; pH value:F = 10.736,P = 0.001;BEecf:F = 67.136,P = 0.000; HCO3-:F = 5.612,P = 0.011), manifesting an obvious combination of respiratory acidosis and metabolic acidosis, and a serious mixed acid-base disturbance was produced.② Compared with corresponding control groups, hemoglobin (Hb) was significantly increased in moderate heatstroke group (g/L: 15.31±1.84 vs. 13.28±0.94,t = 2.791,P = 0.014), Hb and hematocrit (HCT) in severe heatstroke group were significantly increased [Hb (g/L): 16.59±2.52 vs. 13.42±1.15,t = 3.224,P = 0.006; HCT: (53.50±6.63)% vs. (45.50±4.47)%,t = 2.828, P = 0.013], showing that the degree of dehydration was aggravated gradually from mild to serious degree.③ Serum sodium content in mild heatstroke group was normal (t = 0.665,P = 0.517), serum potassium content was lowered significantly (t = -2.526,P = 0.024); serum sodium content in moderate heatstroke group was increased significantly (t = 2.162,P = 0.048), serum potassium content was lowered significantly (t = -5.458,P = 0.000); and serum sodium content in severe heatstroke group rose obviously (U = 12.500,P = 0.038), and most of the rats showed hypokalemia, with a small proportion of rats showed obvious hyperkalemia (U = 19.500,P = 0.195).ConclusionsAcidosis, electrolyte disturbance, respiratory failure and dehydration in heatstroke occurred in dry-heat environment of desert. It indicates that resuscitation should focus on correction of respiratory acidosis, with simultaneous correction of metabolic acidosis, and one should be alert to correct dehydration and electrolyte disturbance. During the moderate phase and the serious phase, correction of aggravated metabolic acidosis should be reinforced, and the prevention and treatment of the severe dehydration and electrolyte disturbance should be undertaken actively.

A research in renal injury of heatstroke rats in dry-heat atmosphere of desert / 中华急诊医学杂志

Objective To observe the function of kidney compromised and histopathological changes of renal tissue in heatstroke rats under the dry-heat atmosphere of desert in order to find the mechanism for provide a rationale of clinical treatment.Methods Forty-eight anaesthetized rats were divided into six groups (n =8 in each group):mild heatstroke group with its control group,moderate heatstroke group with its control group,and severe heatstroke group with its control group.The rats of three heatstroke groups were placed in a dry-heat environment prolonged with 41 ℃ and 10％ humidity,and the three control groups were placed in a room temperature prolonged with 25 ℃ and 35％ humidity.At heatstroke status of each group,arterial blood samples were collected from each group for testing creatine kinase (CK),creatinine (CREAT),uric acid (UA) and urea,kidney tissues and muscle tissues were taken for pathological examinations.Results Pathological examination showed dilatation and congestion of vessels,thrombosis,bleeding,protein casts and endothelium injury were found in the heatstroke rats.In mild heatstroke,the pathological changes mainly manifested as dilatation and congestion of vessels ; in moderate one,the changes mainly manifested as thrombosis; and in severe one,changes mainly manifested as bleeding and protein casts.Muscle tissues presented rhabdomyolysis,especially in severe one.The differences in biomarkers between three different degrees of heatstroke showed statistical significance (CK:F =136.204,P =0.000;CREAT:F =172.865,P=0.000; UA:F=546.454,P=0.000; urea:F=73.823,P=0.000).There was no significant difference in UA between mild heatstroke group and its control group (t =1.943 ;P =0.072),and the differences in rest biomarkers showed statistical significance between each heatstroke group and its control group (P =0.000).Conclusions The kidney injury developed during heatstroke in dry-heat environment of desert suggests that we should be alert to disseminated intravascular coagulation (DIC),myolysis and acute kidney failure,and should monitor the blood biochemical changes closely and treat it energetically,rescuing a heatstroke patient in dry-heat environment of desert.