The role of purslane in modulating diverse effects of high fat diet on biochemical, histological, and molecular parameters of rats' liver / O papel da beldroega na modulação de diversos efeitos da dieta rica em gordura nos parâmetros bioquímicos, histológicos e moleculares do fígado de ratos

Abstract Consuming a high-fat diet causes a harmful accumulation of fat in the liver, which may not reverse even after switching to a healthier diet. Different reports dealt with the role of purslane as an extract against high-fat diet; meanwhile, it was necessary to study the potential role of fresh purslane as a hypolipidemic agent. This study is supposed to investigate further the potential mechanism in the hypolipidemic effect of fresh purslane, by measuring cholesterol 7a-hydroxylase (CYP7A1) and low-density lipoprotein receptor (Ldlr). Rats were divided into two main groups: the first one is the normal control group (n=7 rats) and the second group (n=28 rats) received a high fat diet for 28 weeks to induce obesity. Then the high fat diet group was divided into equal four subgroups. As, the positive control group still fed on a high fat diet only. Meanwhile, the other three groups were received high-fat diet supplemented with a different percent of fresh purslane (25, 50 and 75%) respectively. At the end of the experiment, rats were sacrificed and samples were collected for molecular, biochemical, and histological studies. Current study reported that, supplementation of fresh purslane especially at a concentration of 75% play an important role against harmful effects of high-fat diet at both cellular and organ level, by increasing CYP7A1 as well as Ldlr mRNA expression. Also, there were an improvement on the tested liver functions, thyroid hormones, and lipid profile. Fresh purslane plays the potential role as a hypolipidemic agent via modulation of both Ldlr and Cyp7A, which will point to use fresh purslane against harmful effects of obesity.

Resumo O consumo de uma dieta rica em gordura causa um acúmulo prejudicial de gordura no fígado, que pode não reverter mesmo após a mudança para uma dieta mais saudável. Diferentes relatórios trataram do papel da beldroega como um extrato contra uma dieta rica em gordura; entretanto, foi necessário estudar o papel potencial da beldroega fresca como agente hipolipemiante. Este estudo pretende investigar mais profundamente o mecanismo potencial no efeito hipolipidêmico da beldroega fresca, medindo o colesterol 7a-hidroxilase (CYP7A1) e o receptor de lipoproteína de baixa densidade (Ldlr). Os ratos foram divididos em dois grupos principais: o primeiro é o grupo controle normal (n = 7 ratos) e o segundo grupo (n = 28 ratos) recebeu dieta rica em gorduras por 28 semanas para induzir a obesidade. Em seguida, o grupo de dieta rica em gordura foi dividido em quatro subgrupos iguais. Como, o grupo de controle positivo ainda se alimentava apenas com dieta rica em gordura. Enquanto isso, os outros três grupos receberam dieta rica em gordura suplementada com diferentes porcentagens de beldroegas frescas (25%, 50% e 75%), respectivamente. Ao final do experimento, os ratos foram sacrificados e amostras coletadas para estudos moleculares, bioquímica e histológicos. O estudo atual relatou que a suplementação de beldroegas frescas, especialmente a uma concentração de 75%, desempenha papel importante contra os efeitos prejudiciais da dieta rica em gordura em nível celular e orgânico, aumentando a expressão de CYP7A1 e Ldlr mRNA. Além disso, houve melhora nas funções hepáticas testadas, nos hormônios tireoidianos e no perfil lipídico. Beldroegas frescas desempenham papel potencial como agente hipolipemiante por meio da modulação de Ldlr e Cyp7A, o que apontará para o uso de beldroegas frescas contra os efeitos nocivos da obesidade.

Biochemical and immunohistochemical examination of the effects of ephedrine in rat ovary tissue

Purpose: It was aimed to investigate the biochemical and immunohistochemical effects of ephedrine (EPH) in bilateral ovariectomized rats. Methods: Twenty-four Sprague Dawley female rats were divided into three groups: control group: The abdomen was opened and closed without any treatment; ischemia-reperfusion (IR) group: 2 h of ischemia followed by 2 h of reperfusion were allowed to cause IR injury; IR+EPH group: oral EPH solution (5 mg/kg) was administered for 28 days. Results: Biochemical parameters were statistically significant in group comparisons. Increased interleukin-6 (IL-6) expression, degenerative preantral and antral follicle cells and inflammatory cells around blood vessels were seen in IR group. Negative IL-6 expression was observed in seminal epithelial cells, preantral and antral follicle cells in IR+EPH group. While caspase-3 activity increased in granulosa cells and stromal cells in IR group, caspase-3 expression was negative in preantral and antral follicle cells in the germinal epithelium and cortex in IR+EPH group. Conclusion: The effect of apoptosis, which occurs with the signaling that starts in the cell nucleus, caused the cessation of the stimulating effect at the nuclear level after EPH administration, and a decrease in the antioxidative effect in IR damage and inflammation in the apoptotic process.

Tarantula cubensis extract (Theranekron®) inhibits inflammation in carrageenan-induced acute paw edema in rats / [Extrato de tarântula cubensis (Theranekron®) inibe a inflamação no edema induzido por algas vermelhas na pata de ratos]

The aim of this study was to investigate the anti-inflammatory effect of alcoholic extract of Tarantula cubensis alcoholic extract (TCAE) in experimentally induced inflammation in rats. Fifty-four adult Sprague-Dawley male rats were randomly divided into nine groups. Paw edema was induced by 0.2mL subplantar (s.p.) injection of 1% carrageenan (CAR) into the right hind paw. Rats were treated with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (INDO) (10mg/kg, p.o.) or TCAE at different doses (1, 10 or 100µg/kg) injected s.c. for systemic or s.p. for local anti-inflammatory effect. Saline was used as control. Changes in paw thickness, volume, and weight were calculated as percentages. Formalin-fixed paws were used for histopathological examination. We detected that TCAE applied s.c. at 10µg/kg and 100µg/kg doses resulted in thinner paw thickness, lower paw volume, and lower paw weights four hours after the induction of inflammation when compared with the INDO group (p<0.05). The paw edema inhibitory effect of TCAE applied at a dose of 10µg/kg, s.c. was 68% when compared with the INDO which had an inhibitory effect of 56%. These results were verified with similar histopathological findings. The anti-inflammatory feature of 10µg/kg of TCAE given systematically was similar to the effects of INDO. Our results suggest that TCAE has anti-inflammatory effects by reducing edema and decreasing inflammatory reaction. These results may be attributed to the inhibition of the production of proinflammatory mediators. Thus, TCAE may be considered as a potential anti-inflammatory agent for treating acute inflammatory conditions.

O objetivo deste estudo foi investigar o efeito anti-inflamatório do extrato alcoólico de Tarantula cubensis (TCAE) na inflamação induzida experimentalmente em ratos. Cinqüenta e quatro ratos Sprague-Dawley adultos machos foram divididos aleatoriamente em nove grupos. O edema da pata foi induzido pela injeção de 0,2mL de subplantar (s.p.) de 1% de carragena (CAR) na pata traseira direita. Ratos foram tratados com o medicamento antiinflamatório não esteróide (NSAID) indometacina (INDO) (10mg/kg, p.o.) ou TCAE em doses diferentes (1, 10 ou 100µg/kg) injetado s.c. para efeito sistêmico ou s.p. para efeito antiinflamatório local. A soro fisiológico foi usado como controle. As mudanças na espessura da pata, volume e peso foram calculadas como porcentagens. As patas fixadas com fórmalina foram usadas para exame histopatológico. Detectamos que o TCAE aplicado s.c. em doses de 10µg/kg e 100µg/kg resultou em menor espessura da pata, menor volume da pata e menor peso da pata quatro horas após a indução da inflamação quando comparado com o grupo INDO (p<0,05). O efeito inibidor do edema da pata de TCAE aplicado na dose de 10µg/kg, s.c. foi de 68% quando comparado com o INDO que teve um efeito inibidor de 56%. Estes resultados foram verificados com resultados histopatológicos semelhantes. A característica anti-inflamatória de 10µg/kg de TCAE dada sistematicamente foi semelhante aos efeitos do INDO. Nossos resultados sugerem que o TCAE tem efeitos anti-inflamatórios reduzindo o edema e diminuindo a reação inflamatória. Estes resultados podem ser atribuídos à inibição da produção de mediadores pró-inflamatórios. Assim, o TCAE pode ser considerado como um agente antiinflamatório potencial para o tratamento de condições inflamatórias agudas.

Pin1 aggravates renal injury induced by ischemia and reperfusion in rats via Nrf2/HO-1 mediated endoplasmic reticulum stress

Purpose: To investigate the role of peptidyl-prolyl cis/trans isomerase 1 (Pin1) on renal ischemia-reperfusion (I/R) injury and underlying mechanism. Methods: By establishing the in vitro and in vivo models of renal I/R, the role of Pin1 was explored by using molecular assays. Results: In renal I/R, endogenous Pin1 level was up-regulated in I/R-impaired kidney. Suppression of Pin1 with juglone afforded protection against I/R-mediated kidney dysfunction, and reduced I/R-induced endoplasmic reticulum (ER) stress in vivo. Consistent with the in vivo results, repression of Pin1 with juglone or gene knockdown with si-Pin1 conferred cytoprotection and restricted hypoxia/reoxygenation (H/R)-driven ER stress in HK-2 cells. Simultaneously, further study uncovered that Nrf-2/HO-1 signals was the association between Pin1 and ER stress in response to renal I/R. In addition, Nrf-2/HO-1 signal pathway was inactivated after kidney exposed to I/R, as indicated by the down-regulation of Nrf-2/HO-1 levels. Furthermore, inhibition of Pin1 remarkably rescued the inactivation ofNrf-2/HO-1. Conclusions: Pin1 modulated I/R-mediated kidney injury in ER stress manner dependent on Nrf2-HO-1 pathway in I/R injury.

Experimental model for controlled endoscopic subepithelial vocal fold injury in rats

Purpose: To present a detailed, reproducible, cost-efficient surgical model for controlled subepithelial endoscopic vocal fold injury in the rat model. Methods: Six male Sprague Dawley rats were enrolled in the experiment. The left vocal folds were used to carry out the injury model, and the right vocal fold served as control. After deep sedation, the rats were placed on a custom operating platform. The vocal fold injury by subepithelial stripping was carried out using custom-made microsurgical instruments under endoscopic guidance. Data were analyzed for procedural time and post-procedural pain. Microcomputed tomography (micro-CT) scan and histologic images were obtained to assess the length, area, and depth of injury to the vocal fold. Results: The mean procedural time was 112 s. The mean control vocal fold length was 0.96 ± 0.04 mm. The mean vocal fold injury length was 0.53 ± 0.04 mm. The mean vocal fold surface was 0.18 ± 0.01 mm2 with a mean lesion area of 0.05 ± 0.00 mm2. Mean vocal fold injury depth was 375.4 ± 42.8 µm. The lesion length to vocal fold length ratio was 0.55 ± 0.03, as well as lesion area to vocal fold surface area was 0.29 ± 0.02. Conclusions: Our described experimental vocal fold injury model in rats is found to be fast, safe, cost-efficient, and reproducible with a rapid learning curve.

The neuroprotective effects of Lutongkeli in traumatic brain injury rats by anti-apoptosis mechanism

Purpose: To explore the neuroprotective effects of Lutongkeli (LTKL) in traumatic brain injury (TBI) and detect the related mechanism. Methods: TBI model was established with LTKL administration (2 and 4 g/kg/d, p.o.). Motor function of rats was examined by Rotarod test. Nissl staining was used to show neuron morphology. Furthermore, the disease-medicine common targets were obtained with the network pharmacology and analyzed with Kyoto Encyclopedia of Genes and Genomes. Lastly, the predicted targets were validated by real-time polymerase chain reaction. Results: After LTKL administration, neural behavior was significantly improved, and the number of spared neurons in brain was largely increased. Moreover, 68 bioactive compounds were identified, corresponding to 148 LTKL targets; 2,855 genes were closely associated with TBI, of which 87 overlapped with the LTKL targets and were considered to be therapeutically relevant. Functional enrichment analysis suggested LTKL exerted its pharmacological effects in TBI by modulating multiple pathways including apoptosis, inflammation, etc. Lastly, we found LTKL administration could increase the mRNA level of Bcl-2 and decrease the expression of Bax and caspase-3. Conclusions: This study reported the neuroprotective effect of LTKL against TBI is accompanied with anti-apoptosis mechanism, which provides a scientific explanation for the clinical application of LTKL in the treatment of TBI.

Protective effect and mechanism of Shenkang injection on adenine-induced chronic renal failure in rats

Purpose: To investigate the protective effects of Shenkang injection (SKI) on adenine-induced chronic renal failure (CRF) in rat. Methods: Sprague Dawley rats were randomly divided into five groups: control, model, and SKI groups (5, 10, 20 mL/kg). Rats in model and SKI groups were treated with adenine i.g. at a dose of 150 mg/kg every day for 12 weeks to induce CRF. Twelve weeks later, SKI was administered to the rat i.p. for four weeks. The effects of SKI on kidney injury and fibrosis were detected. Results: SKI inhibited the elevation of the urine level of N-acetyl-b-D-glucosaminidase, kidney injury molecule-1, beta-2-microglobulin, urea protein in CRF rats. The serum levels of uric acid and serum creatinine increased and albumin decreased in the model group, which was prevented by SKI. SKI inhibited the release of inflammatory cytokines and increasing the activities of antioxidant enzymes in serum. SKI inhibited the expression of transforming growth factor-β1, vascular cell adhesion molecule 1, intercellular adhesion molecule 1, collagen I, collagen III, endothelin-1, laminin in kidney of CRF rats. Conclusions: SKI protected against adenine-induced kidney injury and fibrosis and exerted anti-inflammatory, and antioxidant effects in CRF rats.

Genistein improves mitochondrial function and inflammatory in rats with diabetic nephropathy via inhibiting MAPK/NF-κB pathway

Purpose: To investigate the effect of genistein on inflammation and mitochondrial function of diabetic nephropathy. Methods: Diabetic nephropathy model was established in Sprague-Dawley rats. Automatic biochemical analyzer was employed to detect the kidney function index, serum creatinine, serum urea nitrogen, and 24 h-urine protein and blood glucose. Hematoxylin and eosin staining and periodic acid Schiff staining were used to observe renal morphology. Mitochondrial changes and podocyte integrity were monitored by transmission electron microscope. The expression levels of mfn2, NOX4, P53, MAPK, and NF-κB were detected by Western blotting. The changes of mitochondrial membrane potential were measured by JC-1. The level of mfn2 was assessed by immunofluorescence assay. Results: Genistein ameliorated the kidney function with reduced Scr and blood glucose. The expressions of NOX4, MAPK, p65 and p53 were downregulated, while the expression of mnf2 was the opposite in genistein-treated kidneys. Further investigations revealed that genistein reduced expansion of mesangial matrix and oxidative stress, protected podocyte integrity and increased mitochondrial membrane potential. Conclusions: Genistein could alleviate diabetic nephropathy through inhibiting MAPK/NF-κB pathway, improving mitochondrial function and anti-inflammatory.To investigate the effect of genistein on inflammation and mitochondrial function of diabetic nephropathy. Diabetic nephropathy model was established in Sprague-Dawley rats. Automatic biochemical analyzer was employed to detect the kidney function index, serum creatinine, serum urea nitrogen, and 24 h-urine protein and blood glucose. Hematoxylin and eosin staining and periodic acid Schiff staining were used to observe renal morphology. Mitochondrial changes and podocyte integrity were monitored by transmission electron microscope. The expression levels of mfn2, NOX4, P53, MAPK, and NF-κB were detected by Western blotting. The changes of mitochondrial membrane potential were measured by JC-1. The level of mfn2 was assessed by immunofluorescence assay. Genistein ameliorated the kidney function with reduced Scr and blood glucose. The expressions of NOX4, MAPK, p65 and p53 were downregulated, while the expression of mnf2 was the opposite in genistein-treated kidneys. Further investigations revealed that genistein reduced expansion of mesangial matrix and oxidative stress, protected podocyte integrity and increased mitochondrial membrane potential. Genistein could alleviate diabetic nephropathy through inhibiting MAPK/NF-κB pathway, improving mitochondrial function and anti-inflammatory.

Changes of renal histopathology and the role of Nrf2/HO-1 in asphyxial cardiac arrest model in rats

ABSTRACT Purpose To investigate the role of Nrf2/HO-1 in renal histopathological ailments time-dependently in asphyxial cardiac arrest (CA) rat model. Methods Eighty-eight Sprague Dawley male rats were divided into five groups of eight rats each. Asphyxial CA was induced in all the experimental rats except for the sham group. The rats were sacrificed at 6 hours, 12 hours, one day and two days post-CA. Serum blood urea nitrogen (BUN), creatinine (Crtn) and malondialdehyde from the renal tissues were evaluated. Hematoxylin and eosin and periodic acid-Schiff staining were done to evaluate the renal histopathological changes in the renal cortex. Furthermore, Nrf2/HO-1 immunohistochemistry (ihc) and western blot analysis were performed after CA. Results The survival rate of rats decreased in a time-dependent manner: 66.6% at 6 hours, 50% at 12 hours, 38.1% in one day, and 25.8% in two days. BUN and serum Crtn markedly increased in CA-operated groups. Histopathological ailments of the renal cortical tissues increased significantly from 6 hours until two days post-CA. Furthermore, Nrf2/HO-1 expression level significantly increased at 6 hours, 12 hours, and one day. Conclusions The survival rate decreased time-dependently, and Nrf/HO-1 expression increased from 6 hours with the peak times at 12 hours, and one day post-CA.

Protective effects of ischemic postconditioning on skeletal muscle following crush syndrome in the rat

ABSTRACT Purpose To investigate the effect of ischemic postconditioning (IPostC) on skeletal muscle and its optimal protocol. Methods This article is about an animal study of rat model of crush syndrome. Sixty rats were randomized into nine different IPostC intervention groups and a control group. The anesthetized rats were subjected to unilateral hindlimb 3-kg compression with a compression device for 6 h, followed by nine different IPostC intervention protocols. Results Serum levels of creatine kinase (CK) at 3 h post-crush became 2.3-3.9 times among all 10 groups after crush. At 72 h post-crush, serum CK level was reduced to 0.28-0.53 time in all intervention groups. The creatinine (CREA) level in the control group was elevated to 3.11 times at 3 h post-crush and reduced to1.77 time at 72 h post-crush. The potassium (K+) level in the control group was elevated to 1.65 and 1.41 time at 3 and 72 h post-crush, respectively. Conclusions Our IPostC intervention protocols can effectively protect rats from crush-induced elevation of serum CK, CREA, and K+ levels. The timing of IPostC intervention should be as early as possible, to ensure the protective effect.

Cardiac and renal effects of liver cirrhosis in a growing animal model

ABSTRACT Purpose: To assess the biochemical, histological, histomorphometric and molecular effects of biliary duct ligation (BDL) induced liver cirrhosis in the heart and kidneys. Methods: Thirty-two weaning rats (21 days old, 50-70 g) underwent BDL and were divided in four groups (euthanasia after two, four, six, and eight weeks, respectively) and compared to control groups. Results: The animals' hearts of group 3 were bigger than those of the control group (p=0.042), including thinner right ventricle wall, decreased internal diameter of ventricles, and increased perivascular collagen deposition in left ventricle, as well as increased interstitial collagen in right ventricle after six weeks. In the kidneys of groups 3 and 4, bilirubin impregnation in the tubules, hydropic degeneration, loss of nuclei and lack of plasmatic membrane limits were noted. Nitric oxide synthase (NOS) gene expressions were higher in group 1 (p=0.008), and endothelial nitric oxide synthase (eNOS) gene expressions were elevated in all experimental groups (p=0.008, p=0.001, p=0.022, and p=0.013, respectively). In the heart, a decreased expression of eNOS in group 1 (p=0.04) was observed. Conclusions: Liver cirrhosis leads to histological and histomorphometric alterations in the heart and kidneys, with changes in the NOS and eNOS gene expressions, that may suggest a role in the associated myocardial and renal manifestations.

Effect of hyperbaric oxygenation on random rat skin flaps vascularization

ABSTRACT Purpose: To evaluate the effect of hyperbaric oxygenation (HBO) on angiogenesis in random rat skin flaps, by immunoexpression of vascular endothelial growth factor A (VEGF-A). Methods: Forty adult rats were divided into four groups: GE) epilated; GE/HBO) epilated subjected to HBO; GER) epilated submitted to dorsal skin flap; GER/HBO) epilated subjected to dorsal skin flap + HBO. HBO was performed with rats inside a chamber under atmosphere close to 100% oxygen and pressure of 2.4 absolute atmospheres, 2h per day during seven consecutive days. GE and GER groups were placed in the hyperbaric chamber without HBO. Then, under anesthesia, skin flaps were removed and separated into three portions relative to pedicle fixation. The samples were fixed in formalin and processed for paraffin embedding. Histological sections were submitted to immunohistochemistry for VEGF-A detection. The number of immunostained-blood vessels were counted under light microscopy. Results: GE and GE/HBO groups showed normal and similar skin morphology in the three flap portions. A fibrin-leukocyte crust, along with denatured collagen and intense leukocyte infiltrate, was mainly observed in the dermis of the medial and distal flap portions of GER group. Meanwhile, the GER/HBO group presented more regions with intact collagen and small areas of leukocyte infiltrate in the three flap regions. VEGF-A-immunostained blood vessels were largely seen in all regions of GE and GE/HBO groups, whereas no significant differences were found between these groups. A decrease in vascularization was noticed in GER and GER/HBO groups, which was more evident in the most distal portion of the flaps. However, the number of VEGF-A-immunostained blood vessels in GER/HBO group was significantly higher when compared to GER group. Conclusions: Hyperbaric oxygenation was associated with increased angiogenesis and improved viability of rat skin flaps.

Effects of glycerol and sodium pentaborate containing new formulation on sleeve gastrectomy model in rats

ABSTRACT Purpose: The development of cutting surface leakage and postoperative peritoneal adhesions (PPA) after sleeve gastrectomy (SG) are the most serious operative complications. We investigated the effectiveness of the newly developed glycerol and sodium pentaborate containing formulation on the prevention of these complications. Methods: Sixteen Sprague Dawley rats (mean weight 310 ± 50 g, mean age 3 months old) were divided into two groups, consisting of eight rats in each. SG and a double-layer suture technique were performed for each group. In study group, there was the mixture of 2 mL 3% glycerol plus 3% sodium pentaborate formulation, and in the control group 2 mL 0.9% NaCl was injected into the peritoneal cavity. Rats were sacrificed after 30 days, then macroscopic adhesion grade scoring and histopathological evaluations were assessed. Results: Macroscopic PPA scores in the control and study groups were 2.75 ± 0.16 and 1.50 ± 0.327, respectively (p = 0.004). Histopatologic fibrosis scores in the control and study groups were 0.87 ± 0.125 and 2.00 ± 0.26, respectively (p = 0.002). Conclusions: In SG operation model, glycerol plus sodium pentaborate compound decreased PPA formation and also increased stomach cut surface line fibrosis. This new formulation is hopeful for more safe SG operations.

Ferulic acid improves motor function induced by spinal cord injury in rats via inhibiting neuroinflammation and apoptosis

ABSTRACT Purpose To investigate the effect of ferulic acid (FA) on spinal cord injury (SCI)-induced motor dysfunction and to explore the possible pharmacological mechanisms. Methods Adult male Wistar rats were used in our study. SCI was achieved by clipping the spinal cord T9 of the rat by a vascular clip for 2 minutes. The motor function of the rat was evaluated by Basso, Beattie, and Bresnahan scoring method (BBB) and inclined plane test. Hematoxylin and eosin (HE) staining, NISSL staining, and transmission electron microscopic examination were used to evaluate alterations at the histological level. Polymerase chain reaction (PCR), Western blots, and enzyme-linked immunosorbent assays (ELISA) were employed in biochemical analysis. Results The BBB score and inclined plane test score significantly decreased after SCI surgery, whereas chronic FA treatment (dose of 90 mg/kg, i.g.) for 28 days improved SCI-induced motor dysfunction. HE staining showed that SCI surgery induced internal spinal cord edema, but the structural changes of the spinal cord could be reversed by FA treatment. NISSL staining and transmission electron microscopic examination confirmed the improvement of the effect of FA on the injury site. In the biochemical analysis, it could be found that FA inhibitedSCI-induced mRNA and protein overexpression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), as well as iNOS and COX-2 via the modulation of NF-κB level in the spinal cord of SCI rat. Moreover, the SCI-induced decrease of Bcl-2/Bax ratio was also reversed by FA treatment. However, the effect of FA on the expression of Beclin-1 was not statistically significant. Conclusions FA showed a therapeutic effect on SCI, which may be associated with the regulation of neuroinflammation and apoptosis.

Parecoxib mitigates lung ischemia-reperfusion injury in rats by reducing oxidative stress and inflammation and up-regulating HO-1 expression

ABSTRACT Purpose: To investigate the protective effect of parecoxib against lung ischemia-reperfusion injury (LIRI) in rats and the mechanism. Methods: Thirty rats were divided into sham-operated, LIRI and LIRI+parecoxib groups. LIRI model (ischemia for 60 min, followed by reperfusion for 120 min) was constructed in LIRI and LIRI+parecoxib groups. In LIRI+parecoxib group, 10 mg/kg parecoxib was given via femoral vein 15 min before ischemia beginning. At the end of the reperfusion, blood gas analysis, lung wet to dry mass ratio measurement, lung tissue biochemical determination and heme oxygenase-1 (HO-1) protein expression determination were performed. Results: Compared with LIRI group, in LIRI+parecoxib group the oxygenation index was significantly increased, the alveolar-arterial oxygen partial pressure difference was significantly decreased, the lung wet to dry mass ratio was significantly decreased, the lung tissue malondialdehyde content was significantly decreased, the lung tissue superoxide dismutase and myeloperoxidase activities were significantly increased, the lung tissue tumor necrosis factor α and interleukin 1β levels were significantly decreased, and the lung tissue HO-1 protein expression level was significantly increased (all P < 0.05). Conclusions: Parecoxib pretreatment can mitigate the LIRI in rats by reducing oxidative stress, inhibiting inflammatory response and up-regulating HO-1 expression in lung tissue.

Effects of propofol on inflammatory response and activation of p38 MAPK signaling pathway in rats with ventilator-induced lung injury

ABSTRACT Purpose: To investigate the effects of propofol on inflammatory response and activation of p38 mitogen-activated protein kinase (MAPK) signaling pathway in rats with ventilator-associated lung injury (VALI). Methods: Thirty-six Sprague Dawley (SD) rats were divided into control, VALI and VALI+propofol groups. The VALI group received the mechanical ventilation for 2 h. The VALI+propofol group received the mechanical ventilation for 2 h, which was accompanied by intravenous injection of propofol with dose of 8 mg·kg-1·h-1. At the end, the mean arterial pressure (MAP) and blood gas indexes were measured, and the lung wet/dry mass ratio (W/D) and biochemical indexes of lung tissue and bronchoalveolar lavage fluid (BALF) were determined. Results: Compared with VALI group, in VALI+propofol group the blood pH, partial pressure of oxygen, partial pressure of carbon dioxide and MAP were increased, the lung W/D, lung tissue myeloperoxidase activity and total protein concentration, white blood cell count, and tumor necrosis factor α, interleukin 1β and interleukin 6 levels in BALF were decreased, and the p-p38 MAPK protein expression level and phosphorylated p38 MAPK (p-p38 MAPK)/p38 MAPK ratio were decreased. Conclusions: Propofol treatment may alleviate the VALI in rats by reducing the inflammatory response and inhibiting the activation of p38 MAPK signaling pathway.

Hydrogen-rich saline alleviates early brain injury through regulating of ER stress and autophagy after experimental subarachnoid hemorrhage

ABSTRACT Purpose: Subarachnoid hemorrhage (SAH) is a common complication of cerebral vascular disease. Hydrogen has been reported to alleviate early brain injury (EBI) through oxidative stress injury, reactive oxygen species (ROS), and autophagy. Autophagy is a programmed cell death mechanism that plays a vital role in neuronal cell death after SAH. However, the precise role of autophagy in hydrogen-mediated neuroprotection following SAH has not been confirmed. Methods: In the present study, the objective was to investigate the neuroprotective effects and potential molecular mechanisms of hydrogen-rich saline in SAH-induced EBI by regulating neural autophagy in the C57BL/6 mice model. Mortality, neurological score, brain water content, ROS, malondialdehyde (MDA), and neuronal death were evaluated. Results: The results show that hydrogen-rich saline treatment markedly increased the survival rate and neurological score, increased neuron survival, downregulated the autophagy protein expression of Beclin-1 and LC3, and endoplasmic reticulum (ER) stress. That indicates that hydrogen-rich saline-mediated inhibition of autophagy and ER stress ameliorate neuronal death after SAH. The neuroprotective capacity of hydrogen-rich saline is partly dependent on the ROS/Nrf2/heme oxygenase-1 (HO-1) signaling pathway. Conclusions: The results of this study demonstrate that hydrogen-rich saline improves neurological outcomes in mice and reduces neuronal death by protecting against neural autophagy and ER stress.

Resveratrol inhibits TNF-alfa-induced inflammation to protect against renal ischemia/reperfusion injury in diabetic rats

Purpose To examine effects of resveratrol on renal ischemia/ reperfusion injury (I/R) in a streptozotocin (STZ)-induced diabetic rat model. Methods Twenty-four male Sprague Dawley rats were treated with STZ injection for the development of diabetes, and divided into the following groups: Sham group, I/R group and Resveratrol group (n=8). Resveratrol (RSV) was administered at a dose of 10 mg.kg-1.d-1 fourteen days prior to suffering from I/R. Renal function, histology, SOD, MDA, TUNEL assay and expression of TNF-alfa, IL-1beta, NF-kB-P65, COX-2 and Caspase3, Bcl2 and Bax were analyzed. Results Administration of RSV significantly reduced the serum levels of renal dysfunction and injury markers, including creatinine, blood urea nitrogen and MDA; in the other hand, it significantly increased the serum levels of SOD. The protective effect of RSV was also reflected on histologic evaluation. RSV reduced the number of apoptotic cells as determined by TUNEL assay. RSV significantly reduced the protein expression of TNF-alfa, IL-1beta, NF-B-P65, COX-2 and Caspase3, and Bax. Meanwhile, RSV significantly increased the protein expression of Bcl2. Conclusion RSV attenuated I/R-induced renal injury in diabetic rats through the modulation of oxidative stress and TNF-alfa-stimulated inflammation.(AU)

Therapeutic effects of vitamin D on acetic acid-induced colitis in rats

Purpose To analyze the effect of calcitriol treatment on acute colitis in an experimental rat model. Methods A total of 24 adult Sprague Dawley albino rats were randomly separated into 3 equal groups: control group (n:8), colitis group (n:8), calcitriol administered group (n:8). A single dose of acetic acid (1 ml of 4% solution) was administered intrarectally to induce colitis. Group 1 was given 1 ml/kg 0.9% NaCl intraperitoneally; rats belonging to Group 2 were administered calcitriol 1 µg/kg for 5 days. Results Plasma tumor necrosis factor alpha, Pentraxin 3, and malondialdehyde levels were significantly lower in the calcitriol administered colitis group than in the standard colitis group (p 0.01). In the Calcitriol group, there was a significant histological improvement in hyperemia, hemorrhage and necrotic areas in the epithelium compared to the placebo group (p 0.000). Conclusion The findings suggest that calcitriol may be an agent that could be used in acute colitis treatment.(AU)

Effect of a new cross-linked hyaluronan gel on the staple line after sleeve gastrectomy in a rat model

Purpose: To evaluate the effect of a new cross-linked hyaluronan (NCHA) gel on healing of the staple line in an experimental sleeve gastrectomy.Methods: Eighteen rats were randomly divided into three groups. The control group (n = 6) received no medication. In the saline group (n = 6) and NCHA gel group (n = 6), saline and NCHA gel were respectively administered onto the staple line and intraperitoneally into the abdominal cavity after the standard stapling procedure.Results: The fibroblast activity and collagen deposition were significantly higher in the NCHA gel group than in the control group (p = 0.00, p = 0.017) and saline group (p = 0.004, p = 0.015). The tissue hydroxyproline protein level was significantly higher in the NCHA gel group than in the control group (p = 0.041). Adhesion formation was significantly lower in the NCHA gel group than in the control and saline groups (p = 0.015, p = 0.041).Conclusions: New cross-linked hyaluronan gel could be an effective approach to improve staple line wound healing and prevent potential leakage after sleeve gastrectomy. Moreover, NCHA gel helps to prevent adhesion formation without compromising healing of the staple line.(AU)