Ethyl Pyruvate Group Research Articles

Effects of N-acetylcysteine and ethyl pyruvate on ischemia-reperfusion injury in experimental electrical burn model

ObjectivesThis study was planned as a histopathologic evaluation of the effectiveness of ethyl pyruvate (EP) and N-acetylcysteine (NAC) in reducing electric burn–related organ damage in an experimental model. MethodsFour groups of 7 female Wister rats were established. The first was a sham group, the second an electrical burn control group receiving 600 V, the third group received NAC therapy of 20 mg/kg 1 hour after 600 V electrical burn, and the fourth group received 50 mg/kg EP 1 hour after 600 V electrical burn. Heart, kidney, striated muscle, brain, and lung tissues obtained 24 hours postprocedurally were subjected to histopathologic examination, and injury scores were determined. The values determined were then subjected to statistical analysis. ResultsElectrical fire caused significant damage in heart, striated muscle, kidney, and brain tissues. A statistically significant decrease in injury scores in total striated muscle and heart tissue was observed in the 2 treatment groups administered NAC or EP compared to the control group (P= .001). Total kidney injury scores among the groups were significantly lower in the NAC and EP groups compared to the control group (P= .002 and P= .001, respectively). Brain injury examination revealed a significant decrease in injury scores with NAC and EP therapy, both antioxidant agents, in terms of neuron degeneration (P= .004 and P= .001, respectively). ConclusionsElectrical burn was observed to cause injury in heart, striated muscle, kidney, and brain tissue. This injury was reduced by the administration of NAC and EP.

The potential beneficial effects of ethyl pyruvate on diabetic nephropathy: an experimental and ultrastructural study.

Oxidative stress is one of the main causes of diabetic nephropathy, which is a complication of diabetes mellitus (DM). The aim of this study was to investigate the possible role of ethyl pyruvate (EP) in streptozotocin-induced diabetic rats' kidney. Four groups (n = 8) of male Wistar albino rats were used as follows: control group rats received only sodium citrate buffer solution intraperitoneally (ip). The EP group was given 50 mg/kg EP ip. In the DM group, diabetes was induced by streptozotocin. The DM + EP group received 50 mg/kg EP ip. All animals received daily treatment for 14 days, and at the end of the study the kidneys were removed: the left kidney of the rats was used for malondialdehyde (MDA) analysis and the right kidney for histological examination. There was normal appearance of the kidney tissues in the control and the EP-administered groups. In the DM group, there was evident basement membrane thickening and enlargement of mesangial matrix; swelling in some tubular epithelial cells was also noticeable. In the DM+EP administered group, nearly the same appearance as the control group and relative thickening in the glomerular basal membrane were observed. The antioxidant effect of ethyl pyruvate improved the renal structures in the DM + EP group.

Ethyl pyruvate attenuates murine allergic rhinitis partly by decreasing high mobility group box 1 release.

High-mobility group box 1 (HMGB1) protein, a pro-inflammatory DNA-binding protein, meditates inflammatory responses through Toll-like receptor-4 signals and amplifies allergic inflammation by interacting with the receptor for advanced glycation end products. Previous studies have shown that HMGB1 is elevated in the nasal lavage fluids (NLF) of children suffering from allergic rhinitis (AR) and is associated with the severity of this disease. Furthermore, HMGB1 has been implicated in the pathogenesis of lower airway allergic diseases, such as asthma. Ethyl pyruvate (EP) has proven to be an effective anti-inflammatory agent for numerous airway diseases. Moreover, EP can inhibit the secretion of HMGB1. However, few studies have examined the effect of EP on AR. We hypothesized that HMGB1 plays an important role in the pathogenesis of AR and studied it using an AR mouse model. Forty BALB/c mice were divided into four groups: the control group, AR group, 50 mg/kg EP group, and 100 mg/kg EP group. The mice in the AR and EP administration groups received ovalbumin (OVA) sensitization and challenge, whereas those in the control group were given sterile saline instead of OVA. The mice in the EP administration group were given an intraperitoneal injection of EP 30 min before each OVA treatment. The number of nasal rubbings and sneezes of each mouse was counted after final treatment. Hematoxylin-eosin staining, AB-PAS staining, interleukin-4 and 13 in NLF, IgE, and the protein expression of HMGB1 were measured. Various features of the allergic inflammation after OVA exposure, including airway eosinophilia, Th-2 cytokine production, total IgE, and goblet cell hyperplasia were significantly inhibited by treatment with EP and the expression and release of HMGB1 were reduced after EP administration in a dose-dependent manner. These results indicate that HMGB1 is a potential therapeutic target of AR and that EP attenuates AR by decreasing HMGB1 expression.

Protective effect of ethyl pyruvate on ischemia–reperfusion injury in rat ovary: biochemical and histopathological evaluation

BackgroundTo investigate the protective effect of ethyl pyruvate (EP), an anti-oxidant agent, against ischemia–reperfusion injury in a rat model of ovarian torsion, considering biochemical and histopathological aspects. MethodsForty Wistar Albino rats were divided into five groups: Group I, sham operation; Group II, ischemia alone, Group III, ischemia–reperfusion; Group IV, ischemia–reperfusion+50mg/kg EP; and Group V, ischemia–reperfusion+100mg/kg EP. Through laparotomy, 360° torsion was performed and maintained for 3h, and detorsion was maintained for a further 3h. Intraperitoneal EP was given 30min before the surgical procedure. Ovarian tissues and blood samples were obtained after surgery. Malondialdehyde (MDA) and asymmetric dimethyl arginine (ADMA) levels were measured in both plasma and tissue samples. Tissue sections were evaluated histopatologically. Analysis of variance was used for statistical analyses. ResultsIn both serum and tissue samples, ADMA and MDA levels were found to be significantly lower in the EP groups compared with the ischemia alone and ischemia–reperfusion groups (p=0.0001). However, no significant difference was found between groups treated with 50mg/kg or 100mg/kg EP. On histopathological evaluation, the total tissue injury score was found to be lower in rats treated with EP. No significant difference was detected between groups treated with 50mg/kg or 100mg/kg EP. ConclusionEthyl pyruvate may exert positive effects in ischemia–reperfusion injury in cases of ovarian torsion. However, no difference was detected between 50mg/kg and 100mg/kg EP.

Preventing intraperitoneal adhesions with ethyl pyruvate and hyaluronic acid/carboxymethylcellulose: a comparative study in an experimental model

ObjectiveTo compare the effectiveness of ethyl pyruvate (EP) with that of hyaluronic acid+carboxymethyl cellulose (Seprafilm) for the prevention of intraperitoneal adhesions. Seprafilm has been shown to be effective in many experimental and clinical studies. Study designThirty rats were divided into three groups at random, and uterine horn abrasion was performed by laparotomy. One group received no treatment (control group), one group received a single intraperitoneal dose of EP 50mg/kg (EP group), and a 2×1-cm patch of Seprafilm was applied in the third group (Seprafilm group). All rats were killed 14 days after surgery. Macroscopic and histopathological evaluation were performed by a surgeon and a pathologist who were blinded to group allocation. Histopathologically, inflammation, fibroblastic activity, foreign body reaction, collagen proliferation, vascular proliferation, Masson-Trichrome score, matrix metalloproteinase-2 score and vascular endothelial growth factor score were studied. ResultsMedian macroscopic intraperitoneal adhesion scores for the control, EP and Seprafilm groups were 2.8, 1.2 and 1.1, respectively. Multiple comparisons between groups showed a significant difference (p<0.05). In binary comparisons, significant differences were found between the control group and the EP group, and between the control group and the Seprafilm group (p<0.05). No significant difference was found between the adhesion scores for the EP group and the Seprafilm group (p>0.05). After histopathological evaluation, significant differences in all parameters were found between the groups (p<0.05). In the paired comparison, significant differences were found between the control group and the EP group, and between the control group and the Seprafilm group (p<0.0167), but no significant difference was found between the EP group and the Seprafilm group (p>0.0167). ConclusionsIn comparison with the untreated control group, EP and Seprafilm were found to reduce the formation of intraperitoneal adhesions. No significant difference was found between EP and Seprafilm.

Protective effects of ethyl pyruvate in cisplatin-induced nephrotoxicity

This study was performed to investigate the effect of ethyl pyruvate on changes in renal functions and oxidative stress related renal injury caused by cisplatin (cis-dichlorodiammine platinum-II; CDDP).Male Wistar albino rats were divided into four groups (n = 8): (1) control group (1 ml Ringer's lactate solution i.p.); (2) ethyl pyruvate (EP) group (50 mg/kg Ringer's EP solution (REPS) i.p.); (3) cisplatin group (a single dose of cisplatin (5 mg/kg, i.p.); and (4) cisplatin + EP group (a single dose of cisplatin (5 mg/kg, i.p.) + REPS 50 mg/kg/day, i.p.) for five days. At the sixth day, kidneys of rats were mounted to a Langendorff apparatus. Renal perfusion pressures were recorded. Blood samples were taken for serum urea, creatinine, total oxidant status (TOS), total antioxidant status (TAS) and oxidative stres index (OSI) evaluations. Kidney tissues were obtained for malondialdehyde (MDA) analyses and histopathological examination.Perfusion pressures, serum urea, creatinine, TOS, OSI and tissue MDA levels were found significantly higher, whereas TAS was notably lower in cisplatin group. Histopathological examination showed apparent renal paranchymal injury in cisplatin group. In cisplatin + REPS group, perfusion pressures, serum urea, creatinine and tissue MDA levels were decreased. Moreover, EP co-administration provided less inflammatory cell infiltration, tubular dilatation, whereas TOS, TAS and OSI improved significantly versus cisplatin group.These findings show that EP has protective effects against cisplatin nephrotoxicity.

Effects of ethyl pyruvate on cardiac function recovery and apoptosis reduction after global cold ischemia and reperfusion.

The present study used an in vitro model of cold cardioplegia in isolated working rat hearts to evaluate the possible role of ethyl pyruvate (EP) in promoting cardiac function and preventing apoptosis. Two groups of rats were evaluated; the EP (2 mM EP; n=8) and control (n=8) groups. Isolated rat hearts were perfused with Krebs-Henseleit buffer (KHB) for 30 min, arrested with cardioplegic solution and stored for 4 h in B21 solution at 4°C. The hearts were reperfused with KHB for 45 min. EP was added to the cardioplegic and storage solutions and also to KHB for reperfusion. Cardiac parameters of the heart rate, including left ventricular systolic pressure, left ventricular end-diastolic pressure, left ventricular developed pressure and maximal rise rate of the left ventricular pressure, were monitored. In addition, coronary flow, adenosine triphosphate (ATP) levels and malondialdehyde (MDA) content were recorded and apoptotic cell determination was detected. The functional parameters in the EP group were significantly higher compared with those in the control group during the reperfusion period (P<0.05). In addition, ATP levels were higher in the EP group than in the control group and the content of MDA was lower in the EP group than in the control group. A concentration of 2 mM EP significantly reduced the number of apoptotic cells in the EP group compared with that of the control group (P<0.05). Therefore, EP significantly preserved cardiac function, enhanced tissue ATP levels, attenuated myocardial oxidative injury and markedly reduced apoptosis following myocardial ischemia in an in vitro model of 4 h of cold cardioplegia and reperfusion.

Role of Ethyl Pyruvate in Systemic Inflammatory Response and Lung Injury in an Experimental Model of Ruptured Abdominal Aortic Aneurysm

Objectıve. The purpose of this study is to evaluate the effect of ethyl pyruvate (EP) on systemic inflammatory response and lung injury in an experimental rat model of ruptured abdominal aortic anurysm (RAAA). Methods. Anaesthetized 30 Sprague-Dawley male rats were randomized to sham (Sh n : 6) (Sh + EP n : 6) or shock and clamp (S/C) groups (S/C n : 9) (S/C + EP n : 9). In the S/C and S/C + EP groups, hemorrhagic shock, lower torso ischemia, and reperfusion were created, S/C group was given 1 mL saline and S/C + EP group was given 40 mg/kg EP. At the end of reperfusion process some biochemical and histological parameters were studied in serum and lung tissues. Results. An increase was observed in all parameters except interleukin-6 (IL-6) in the S/C group in comparison to the sham groups. In the S/C + EP group, serum myeloperoxydase (MPO), malondialdehyde (MDA), and tumor necrosis factor alpha (TNF-α) as well as lung MPO and MDA values decreased significantly (P < 0.016). In the lung tissues, histological injury scores and lung tissue wet/dry ratio were significantly decreased in the S/C + EP group as compared to the S/C group (P < 0.016). Conclusions. Ethyl pyruvate may reduce systemic inflammatory response and lung injury which resulted from shock and ischemia/reperfusion in an experimental model of RAAA.

Effect of Ethyl Pyruvate on Paclitaxel-Induced Neuropathic Pain in Rats

BackgroundAlthough paclitaxel is a widely used chemotherapeutic agent for the treatment of solid cancers, side effects such as neuropathic pain lead to poor compliance and discontinuation of the therapy. Ethyl pyruvate (EP) is known to have analgesic effects in several pain models and may inhibit apoptosis. The present study was designed to investigate the analgesic effects of EP on mechanical allodynia and apoptosis in dorsal root ganglion (DRG) cells after paclitaxel administration.MethodsRats were randomly divided into 3 groups: 1) a control group, which received only vehicle; 2) a paclitaxel group, which received paclitaxel; and 3) an EP group, which received EP after paclitaxel administration. Mechanical allodynia was tested before and at 7 and 14 days after final paclitaxel administration. Fourteen days after paclitaxel treatment, DRG apoptosis was determined by activated caspase-3 immunoreactivity (IR).ResultsPost-treatment with EP did not significantly affect paclitaxel-induced allodynia, although it tended to slightly reduce sensitivities to mechanical stimuli after paclitaxel administration. After paclitaxel administration, an increase in caspase-3 IR in DRG cells was observed, which was co-localized with NF200-positive myelinated neurons. Post-treatment with EP decreased the paclitaxel-induced caspase-3 IR. Paclitaxel administration or post-treatment with EP did not alter the glial fibrillary acidic protein IRs in DRG cells.ConclusionsInhibition of apoptosis in DRG neurons by EP may not be critical in paclitaxel-induced mechanical allodynia.

Glycyrrhizin protects against porcine endotoxemia through modulation of systemic inflammatory response

IntroductionGlycyrrhizin (GL) was recently found to suppress high-mobility group box 1 (HMGB1)-induced injury by binding directly to it. However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear.MethodsTwenty-one pigs were divided into four groups: sham group (n = 3), control group (n = 6), ethyl pyruvate group (n = 6) and glycyrrhizin group (n = 6). Pigs were anesthetized, mechanically ventilated, monitored and given a continuous intravenous infusion of lipopolysaccharide (LPS). Twelve hours after the start of the LPS infusion, ethyl pyruvate (30 mg/kg/hr) or glycyrrhizin (1 mg/kg/hr) was administered for 12 hours. Systemic and pulmonary hemodynamics, oxygen exchange, and metabolic status were measured. The concentrations of cytokines in serum and the corresponding gene and protein expressions in tissue samples from liver, lungs, kidneys, small intestine and lymph nodes were measured.ResultsGL maintained the stability of systemic hemodynamics and improved pulmonary oxygen exchange and metabolic status. GL also attenuated organ injury and decreased the serum levels of HMGB1 and other pro-inflammatory cytokines by inhibiting their gene and protein expression.ConclusionsGL improved systemic hemodynamics and protected vital organs against porcine endotoxemia through modulation of the systemic inflammatory response. By reducing the serum level and gene expression of HMGB1 and other pro-inflammatory cytokines, GL may become a potential agent for the treatment of sepsis.

A comparison of the effects of N-acetylcysteine and ethyl pyruvate on experimental testicular ischemia-reperfusion injury

To compare the effects of N-acetylcysteine (NAC) and ethyl pyruvate (EP) on experimental testicular ischemia-reperfusion (I/R) injury. Randomized, controlled, experimental study. University hospital. Twenty-four mature male Wistar rats. Rats were divided into four groups: control group, torsion-detorsion (T/D) group, EP group, and NAC group. In the pretreatment of the NAC and EP groups, 20 mg/kg NAC and 50 mg/kg EP were given intraperitoneally (IP) 30 minutes before detorsion. Serum ischemia-modified albumin (IMA), tissue and serum malondialdehyde, and myeloperoxidase activity levels and histopathological damage scores were then compared. Ethyl pyruvate and N-acetylcysteine exhibited a protective effect against I/R injury. Of the biochemical parameters evaluated as a result of testicular I/R, only IMA levels were significantly elevated. There was a strong and significant correlation between serum IMA levels and histopathological injury scores, and the increase in serum IMA level exhibited a strong parallel with the increase in histopathological injury. In the EP group, although the histopathological injury score was similar to that of the control group, serum IMA levels were significantly elevated. Both NAC and EP, the effects of which on I/R injury are evaluated in the present study, reduce such injury in testicular torsion-detorsion. Comparing their effects on IMA levels, NAC may be regarded as a relatively more effective treatment than EP.

Ethyl pyruvate protects against myocardial ischemia/reperfusion injury via mitochondrial membrane potential dependent and anti‐apoptotic mechanisms

PurposeA role Ethyl pyruvate (EP) in ischemia/reperfusion (I/R) injury is not clear. We investigated whether EP could inhibit cardiac myocyte apoptosis and reduce mitochondrial injury in the ischemic/reperfused heart of the mice.MethodsMale C57BL/6 mice of 12–15 weeks of age were subjected to 25 min of ischemia followed by 45 min of reperfusion. A modified KH perfusion fluid was used, contained except where EP levels were varied. JC‐1 staining flow cytometry was used to examine mitochondrial membrane potential. We investigated mitochondrial structure, apoptosis rate and Bcl‐2, Bax, Caspase‐3 proteins. RT‐PCR was used to determine the expression of P38MAPK mRNA and JNK mRNA. Western blotting was used to measure the expression of P38MAPK, JNK and NFκB P65.ResultsOur results show that 4.0 mM EP group increased LVDP recovery rate and decreased mitochondrial ultrastructural damage as compared to other EP groups. The apoptosis rate and PCI of Bax, Caspase‐3 proteins in the 4.0 mM EP group were decreased, while the PCI of Bcl‐2 protein was increased. The expression of P38MAPK mRNA, JNK mRNA and protein of P38MAPK, JNK and NFκB P65 in free EP group was increased. The rate of loss Δψm cells in the 4.0 mM EP group was lower than in the other groups.ConclusionOur dates suggest that the EP plays an important role in protection of the myocardium against I/R injury and may represent a novel therapeutic target.

Beneficial Effects of Ethyl Pyruvate through Inhibiting High-Mobility Group Box 1 Expression and TLR4/NF-κB Pathway after Traumatic Brain Injury in the Rat

Ethyl pyruvate (EP) has demonstrated neuroprotective effects against acute brain injury through its anti-inflammatory action. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from dying cells. This study was designed to investigate the protective effects of EP against secondary brain injury in rats after Traumatic Brain Injury (TBI). Adult male rats were randomly divided into three groups: (1) Sham + vehicle group, (2) TBI + vehicle group, and (3) TBI + EP group (n = 30 per group). Right parietal cortical contusion was made by using a weight-dropping TBI method. In TBI + EP group, EP was administered intraperitoneally at a dosage of 75 mg/kg at 5 min, 1 and 6 h after TBI. Brain samples were harvested at 24 h after TBI. We found that EP treatment markedly inhibited the expressions of HMGB1 and TLR4, NF-κB DNA binding activity and inflammatory mediators, such as IL-1β, TNF-α and IL-6. Also, EP treatment significantly ameliorated beam walking performance, brain edema, and cortical apoptotic cell death. These results suggest that the protective effects of EP may be mediated by the reduction of HMGB1/TLR4/NF-κB-mediated inflammatory response in the injured rat brain.

Effect of Ethyl Pyruvate on Physical and Immunological Barriers of the Small Intestine in a Rat Model of Sepsis

Physical and immunologic barriers of the small intestine play an important role in development and treatment of sepsis, so a rat model of sepsis was used to investigate the effect of ethyl pyruvate (EP) on the barriers. Male Wistar rats were divided into sham operated, cecal ligation and puncture, and EP groups. Survival and bacterial translocation were measured in response to EP administration. Physical barrier (including mitochondria of enterocyte, tight junction, microvilli, and the grade of small intestinal mucosa damage) and immunologic barrier (including distribution of T-cell subgroups in small intestinal villi, proportion of T-cell subgroups in mesenteric lymph nodes and spleens, proliferation and cytokines release of splenocytes) were determined by electron and light microscopy, immunohistochemistry, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Sepsis induced morphologic alteration and immunosuppression in the small intestine. EP administration can prevent these changes, especially immunologic change. Distribution of CD4+ T cells in villi, proportions of CD4+ T cells in mesenteric lymph nodes and spleens, and proliferative capacity of splenocytes were increased in rats treated with EP. Interferon-gamma and Interleukin-4 release were also modulated. Moreover, EP improved survival from 37.1% to 57.1% and reduced bacterial translocation. EP administration ameliorated physical and immunologic barriers dysfunction of small intestine in a rat model of sepsis. EP may be used to treat sepsis as an immunologic modulator.

The Role of High-Mobility Group Box–1 in Renal Ischemia and Reperfusion Injury and the Effect of Ethyl Pyruvate

Purpose High mobility group box-1(HMGB1) was identified as a DNA-binding protein that functions as a cofactor for proper transcriptional regulation in somatic cells. Extracellular HMGB1 acts as a potent proinflammatory cytokine that contributes to the pathogenesis of diverse inflammatory and infectious disorders. Ethyl pyruvate (EP), a stable aliphatic ester derived from pyruvic acid, was first described as a pharmacological inhibitor of HMGB1 secretion. We designed this study to identify changes in HMGB1 expression in rat kidney tissues after ischemia reperfusion injury and effects of EP on the expression of HMGB1. Materials and Methods Sprague-Dawley rats (200–300 g) were subjected to 40 minutes of renal warm ischemia. The animals were divided into 3 groups: sham group without warm ischemia, EP group (EP given before ischemia), and ischemic control group. Kidneys were harvested and serum creatinine and TNF-α measured at 6 hours, 1 day, 3 days, and 5 days after reperfusion. We performed immunohistochemical staining of HMGB1. Results Serum creatinine and TNF-α level were elevated in the ischemic control group and the EP injection group. In the EP injection group, serum creatinine and TNF-α levels were lower than the ischemic control group. In the 40-minute ischemia-reperfusion model, HMGB1 expression increased at 6 hours after reperfusion and decreased gradually at 1, 3, and 5 days after reperfusion. HMGB1 expression was more distinct at the outer medullary area. intraperitoneal EP injection had no effect on HMGB1 expression. Conclusion From these results, we deduced that the preventive effect of EP on rat kidney ischemia-reperfusion injury was not due to the decreased expression of HMGB1 but the prevention of HMGB1 release.

Effects of ethyl pyruvate on myocardial apoptosis and expression of Bcl-2 and Bax proteins after ischemia-reperfusion in rats

In order to study the effects of ethyl pyruvate on cardiomyocyte apoptosis following ischemia/reperfusion (I/R) in vitro and the expression of Bcl-2 and Bax proteins, isolated rat hearts were perfused in a Langendorff model. Twenty-four rats were randomly divided into 3 groups (n=8 in each group): control group was perfused for 120 min. In the I/R group, after 30 min stabilization the injury was induced by 30 min global ischemia followed by 60 min reperfusion. Ethyl pyruvate (EP) group was set up with the same protocol as I/R group except that it was supplied with 2 mmol/L EP 15 min before ischemia and throughout reperfusion. Myocardial malonaldehyde (MDA) content was measured. Myocardial apoptotic index (AI) was tested by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. The expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in cardiac myocytes was detected by immunohistochemistry. As compared with control group, the content of MDA, myocardial AI and the expression of Bcl-2, Bax proteins were increased significantly in I/R group, but the content of MDA, myocardial AI and the expression of Bax protein were decreased obviously and the expression of Bcl-2 protein was up-regulated in EP group (P<0.05). These results demonstrate that EP could inhibit apoptosis of cardiac myocytes possibly via alleviating oxidative stress, up-regulating Bcl-2 and down-regulating Bax proteins.

Ethyl Pyruvate Ameliorates Liver Injury Secondary to Severe Acute Pancreatitis

Ethyl pyruvate (EP) is capable of significantly decreasing serum alanine aminotransferase and reducing hepatic necrosis in a murine model of severe acute pancreatitis (SAP); however, the working mechanism is still unclear. This study aims to elucidate the underlying mechanism of EP solution ameliorating SAP-induced liver injury and provide a new therapeutic agent to treat liver injury. Acute necrotizing pancreatitis was induced in C57Bl/6 male mice by feeding the animals a choline-deficient diet supplemented with 0.5% ethionine for 24 h; then the animals were challenged with 7 hourly 50 mug/kg cerulein i.p. injections and a single i.p. injection of Escherichia coli lipopolysaccharide (4 mg/kg). Two hours after the injection of lipopolysaccharide, 40 mg/kg EP, the same volume of Ringers lactate solution (RLS), or saline solution were i.p. injected to animals of EP, RLS, and control groups every 6 h for a total 48-h period. When mice were treated with EP, hepatic mRNA expression of tumor necrosis factor-alpha, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 was significantly lower than that in pancreatitis mice treated with RLS. Compared to RLS treatment, treatment with EP significantly decreased the number of inflammatory cell infiltration and markedly inhibited hepatic nuclear factor-kappa B DNA binding; EP therapy dramatically inhibited high motility group B1 release from inflamed hepatic tissue and significantly decreased the concentration of hepatic tissue malondialdehyde, an oxidative stress parameter. EP treatment also significantly improved body circulating blood volume. EP is a potent anti-inflammatory and anti-oxidative agent to ameliorate hepatic local inflammatory response and resultantly decreases liver injury secondary to SAP.

The effect of ethyl pyruvate on dapsone-induced methemoglobinemia in rats

Introduction. Dapsone induces methemoglobinemia by oxidant stress; ethyl pyruvate (EP) is an antioxidant and radical oxygen species scavenger. This study was conducted to evaluate the effect of EP on methemoglobinemia induced by dapsone. Methods. Male Sprague–Dawley rats were divided into an EP group and a control group. Rats in the EP group were administered dapsone (40 mg/kg) via the stomach and then EP (40 mg/kg) was injected intraperitoneally. Rats in the control group were administered dapsone followed by Ringer's lactate solution. Methemoglobin concentrations were measured at 90, 180, and 360 min after dapsone administration. Results. Methemoglobin concentrations were not different between time points in the control group. However, in the EP group, the methemoglobin concentrations were significantly lower than those of the control group at 90 and 180 min, but this difference was no longer apparent at 360 min. Conclusion. A single intraperitoneal dose of EP was able to reduce methemoglobinemia induced by dapsone for a short period of time, but this effect was not sustained.

Effect of ethyl pyruvate on renal high mobility group box-1 protein expression and acute kidney injury in rats with delayed resuscitation after thermal injury

To investigate the effect of ethyl pyruvate (EP) on high mobility group box-1 protein (HMGB1) expression in renal tissue and acute kidney injury in rats with delayed resuscitation after thermal injury. Seventy-eight Wistar rats subjected to 30% total body surface area full-thickness thermal injury followed with delayed resuscitation were divided into 3 groups: sham group (n = 18), injury group (n = 30) and EP group (n = 30). Renal tissue and blood samples were harvested to determine HMGB1 mRNA as well as its protein expression and renal function parameter at the 8, 24, 72 h post the "injury". HMGB1 mRNA was semi-quantitatively measured by reverse transcription polymerase chain reaction taking GAPDH as an internal standard, and HMGB1 protein expression was determined by Western blot and immunohistochemistry. Blood urea nitrogen (BUN) levels were measured with automatic biochemistry analyzer. The pathological changes of renal tissues were examined using HE staining. Compared with sham controls, both mRNA and protein expressions of HMGB1 in injury group were significantly enhanced in kidneys at 8 - 72 h after thermal injury (P < 0.05), meanwhile serum BUN levels were markedly increased (P < 0.05). Compared with injury group, the renal HMGB1 mRNA and protein expressions were markedly down-regulated in EP group at 8 h, 24 h and 72 h post injury (P < 0.05), respectively, and meanwhile serum BUN levels were reduced significantly (P < 0.05). Inflammatory cell infiltration was found in renal tissues following injury, and kidney injury was markedly alleviated after treatment with EP. It indicated that HMGB1 appears to be involved in the pathogenesis of post-burn acute kidney injury. Treatment with EP reduces renal HMGB1 expression, and protects against acute kidney injury secondary to delayed resuscitation after major burns.

The Effect of Ethyl Pyruvate on Oxidative Stress in Intestine and Bacterial Translocation After Thermal Injury

Thermal injury causes a breakdown in the intestinal mucosal barrier due to ischemia reperfusion injury, which can induce bacterial translocation (BT), sepsis, and multiple organ failure in burn patients. The aim of this study was to investigate the effect of ethyl pyruvate (EP) on intestinal oxidant damage and BT in burn injury. Thirty-two rats were randomly divided into four groups. The sham group was exposed to 21 degrees C water and injected intraperitoneal with saline (1 mL/100 g). The sham + EP group received EP (40 mg/kg) intraperitoneally 6 h after the sham procedure. The burn group was exposed to thermal injury and given intraperitoneal saline injection (1 mL/100 g). The burn + EP group received EP (40 mg/kg) intraperitoneally 6 h after thermal injury. Twenty-four hours later, tissue samples were obtained from mesenteric lymph nodes, spleen, and liver for microbiological analysis and ileum samples were harvested for biochemical analysis. Thermal injury caused severe BT in burn group. EP supplementation decreased BT in mesenteric lymph nodes and spleen in the burn + EP group compared with the burn group (P < 0.05). Also, burn caused BT in liver, but this finding was not statistically significant among all groups. Thermal injury caused a statistically significant increase in malondialdehyde and myeloperoxidase levels, and EP prevented this effects in the burn + EP group compared with the burn group (P < 0.05). Our data suggested that EP can inhibit the BT and myeloperoxidase and malondialdehyde production in intestine following thermal injury, suggesting anti-inflammatory and anti-oxidant properties of EP.