ascorbic-acid and Pancreatitis

The Manchester 'oxidant stress' hypothesis for the development of pancreatitis accommodates published information on both chronic pancreatitis and acute pancreatitis. Oxidant stress, mainly from reactive xenobiotic metabolites, is perceived as the pivotal pre-morbid problem in chronic pancreatitis and, by depleting glutathione, targets the exocytosis mechanism of the pancreatic acinar cell. Inhalation exposure to petrochemical products is identified as an independent risk factor in patients at Manchester Royal Infirmary, where some 50% of patients referred have non-alcoholic disease. This paper describes the development of antioxidant therapy, using supplements of methionine, vitamin C and selenium, and its validation in a placebo-controlled trial, followed by a retrospective cross-sectional study in 94 consecutive patients for an average of 30 months. Antioxidant therapy emerges as a safe and effective medical alternative to surgery for painful chronic pancreatitis.

Topics: Antioxidants; Ascorbic Acid; Chronic Disease; Cross-Sectional Studies; Humans; Methionine; Pancreatitis; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Selenium; United Kingdom

Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis.. We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty-three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE-II score and hospital site, and delivered groups that were similar at baseline.. Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome.. This study provides no evidence to justify continued use of n-acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study.

Topics: Acetylcysteine; Acute Disease; Adult; Aged; Antioxidants; APACHE; Ascorbic Acid; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Oxidative Stress; Pancreatitis; Selenium; Treatment Outcome

Patients with chronic pancreatitis (CP) typically suffer intractable abdominal pain that is resistant to most analgesic strategies. Recent research indicates that the pain of CP may be in part due to oxygen free radical induced pancreatic damage. Using a randomized, double-blind, placebo-controlled crossover trial, we evaluated the efficacy of a combined antioxidant preparation in the management of CP. Patients with confirmed chronic pancreatitis (N = 36) were randomized to receive treatment with either Antox, which contains the antioxidants selenium, betacarotene, L-methionine, and vitamins C and E, or placebo for 10 weeks. Each group of patients then switched to receive the alternative treatment for a further 10 weeks. Markers of antioxidant status were measured by blood sampling, whereas quality of life and pain were assessed using the SF-36 questionnaire. Nineteen patients completed the full 20 weeks of treatment. Treatment with Antox was associated with significant improvements in quality of life in terms of pain (+17 antioxidant vs. -7 placebo), physical (+9 vs. -3) and social functioning (+8 vs. -7), and general health perception (+10 vs. -3). We conclude that treatment with antioxidants may improve quality of life and reduce pain in patients suffering from chronic pancreatitis.

Topics: Abdominal Pain; Adult; Aged; Antioxidants; Ascorbic Acid; Attitude to Health; beta Carotene; Chronic Disease; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Methionine; Middle Aged; Pain Measurement; Pain, Intractable; Pancreatitis; Placebos; Quality of Life; Selenium; Treatment Outcome; Vitamin E

This clinical study compared the dynamics of antioxidants levels in patients with acute pancreatitis (AP), patients operated for colorectal cancer (CA), and healthy control subjects.. This prospective descriptive study enrolled 21 AP and 14 CA patients and 17 healthy controls. Blood was collected from AP patients on days 1, 5, and 9 and from CA patients before surgery and on days 1, 5, and 9 after surgery. We measured concentrations of selenium in plasma, red blood cells (RBCs), and big-toe nails, vitamin A (retinol) in serum, alpha-tocopherol in serum and in RBCs, vitamin C in serum, concentration ratio of 9,11- and 10,12-octadecanoic acids to linoleic acid in RBC membrane, activity of superoxide dismutase, and glutathione peroxidase in RBCs.. Plasma concentrations of selenium, vitamin A, and vitamin C were significantly lower in AP and CA patients than in healthy controls over the monitored period (P < 0.05). Patients with severe AP had a significantly lower concentration of selenium in RBCs than did healthy controls and CA patients (P < 0.05). The concentration of selenium in toe nails of AP patients was significantly lower than that in CA patients and healthy controls (P < 0.001). The marker of increased reactive oxygen species activity the ratio of 9,11- and 10,12-octadecanoic acids to linoleic acid in RBCs was significantly higher in AP and CA patients than in healthy controls (P < 0.05).. Low levels of measured antioxidants and increased activity of reactive oxygen species occurred during the course of AP. These findings applied in particular to patients who had severe AP. Levels of measured antioxidants seemed to be similar in AP and CA patients except for lower levels of selenium in toe nails in AP patients and lower selenium concentrations in RBCs in patients with severe AP.

Topics: Acute Disease; Acute-Phase Reaction; Adult; Aged; Antioxidants; Ascorbic Acid; Biomarkers; Colorectal Neoplasms; Erythrocytes; Female; Glutathione Peroxidase; Humans; Male; Middle Aged; Nails; Pancreatitis; Prospective Studies; Reactive Oxygen Species; Selenium; Superoxide Dismutase; Vitamin A

To observe the therapeutic efficacy of high-dose Vitamin C (Vit. C) on acute pancreatitis (AP), and to explore its potential mechanisms.. Eighty-four AP patients were divided into treatment group and control group, 40 healthy subjects were taken as a normal group. In the treatment group, Vit. C (10 g/day) was given intravenously for 5 days, whereas in the control group, Vit. C (1 g/day) was given intravenously for 5 days. Symptoms, physical signs, duration of hospitalization, complications and mortality rate were monitored. Meanwhile, serum amylase, urine amylase and leukocyte counts were also determined. The concentration of plasma vitamin C (P-VC), plasma lipid peroxide (P-LPO), plasma vitamin E (P-VE), plasma beta-carotene (P-beta-CAR), whole blood glutathione (WB-GSH) and the activity of erythrocyte surperoxide dimutase (E-SOD) and erythrocyte catalase (E-CAT) as well as T lymphocyte phenotype were measured by spectrophotometry in the normal group and before and after treatment with Vit. C in the treatment and the control group.. Compared with the normal group, the average values of P-VC, P-VE, P-beta-CAR, WB-GSH and the activity of E-SOD and E-CAT in AP patients were significantly decreased and the average value of P-LPO was significantly increased, especially in severe acute pancreatitis (SAP) patients (P<0.05. P-VC, P=0.045; P-VE, P=0.038; P=0.041; P-beta-CAR, P=0.046; WB-GSH, P=0.039; E-SOD, P=0.019; E-CAT, P=0.020; P-LPO, P=0.038). Compared with the normal group, CD3 and CD4 positive cells in AP patients were significantly decreased. The ratio of CD4/CD8 and CD4 positive cells were decreased, especially in SAP patients (P<0.05. CD4/CD8, P=0.041; CD4, P =0.019). Fever and vomiting disappeared, and leukocyte counts and amylase in urine and blood become normal quicker in the treatment group than in the control group. Moreover, patients in treatment group also had a higher cure rate, a lower complication rate and a shorter in-ward days compared with those in he control group. After treatment, the average value of P-VC was significantly higher and the values of SIL-2R, TNF-alpha, IL-6 and IL-8 were significantly lower in the treatment group than in the control group (P<0.05 P-VC, P=0.045; SIL-2R, P=0.012; TNF-alpha, P=0.030; IL-6, P=0.015; and IL-8, P=0.043). In addition, the ratio of CD4/CD8 and CD4 positive cells in the patients of treatment group were significantly higher than that of the control group after treatment (P<0.05. CD4/CD8, P=0.039; CD4, P=0.024).. High-dose vitamin C has therapeutic efficacy on acute pancreatitis. The potential mechanisms include promotion of anti-oxidizing ability of AP patients, blocking of lipid peroxidation in the plasma and improvement of cellular immune function.

Topics: Acute Disease; Adult; Aged; Antioxidants; Ascorbic Acid; Cytokines; Female; Humans; Immunity, Cellular; Injections, Intravenous; Lipid Peroxidation; Male; Middle Aged; Pancreatitis

To observe outcome in a cohort of patients with severe acute pancreatitis receiving multiple anti-oxidant therapy.. An observational study was carried out in 46 consecutive patients with acute pancreatitis fulfilling current Atlanta consensus criteria for severe disease. All patients received multiple anti-oxidant therapy based on intravenous selenium, N-acetylcysteine and ascorbic acid plus beta-carotene and alpha-tocopherol delivered via nasogastric tube. Principal outcomes were the effect of anti-oxidant supplementation on anti-oxidant levels, morbidity and mortality in patients on anti-oxidant therapy, case-control analysis of observed survival compared to predicted survival derived from logistic organ dysfunction score (LODS), logistic regression analysis of factors influencing outcome and side effect profile of anti-oxidant therapy.. Paired baseline and post-supplementation data were available for 25 patients and revealed that anti-oxidant supplementation restored vitamin C (P = 0.003) and selenium (P = 0.028) toward normal. In univariate survival analysis, patient survival to discharge was best predicted by admission APACHE-II score with relative risk of death increasing 12.6% for each unit increase (95% CI 6.0% to 19.6%). The mean LODS calculated on admission to hospital was 3.7 (standard error of the mean 4.1) giving a predicted mortality for the cohort of 21%. The observed in-hospital mortality was 43%.. Case-control analyses do not appear to demonstrate any benefit from the multiple anti-oxidant combination of selenium, N-acetylcysteine and ascorbic acid in severe acute pancreatitis.

Topics: Acetylcysteine; Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Oxidative Stress; Pancreatitis; Selenium; Survival Rate

Four indices of free radical activity were measured in fasting serum/plasma samples from 14 consecutive blacks with clinically quiescent chronic pancreatitis and 15 outwardly healthy hospital personnel at Soweto, the township near Johannesburg in South Africa. The patients had higher serum levels than did controls of lipid isomerisation (P < 0.002) and peroxidation (P < 0.05) markers, with lower plasma levels of glutathione (P < 0.0001) and bioactive fraction of vitamin C (P < 0.002). Lipid peroxide and non-bioavailable vitamin C concentrations in Sowetan patients were significantly higher than in their counterparts from Manchester, UK (P < 0.0001, P < 0.0005, respectively). These differences mirrored those in controls in that outwardly healthy Sowetans had much higher serum lipid peroxide levels than Manchester controls (P < 0.001) and much lower plasma concentration of vitamin C (P < 0.001) and hence of the bioavailable fraction ascorbate (P < 0.0002). Heightened free radical activity is thus a common denominator in chronic pancreatitis irrespective of geography, or putative aetiological factors whether alcoholism or idiopathic, since that ratio was approximately 95:5 at Johannesburg and 50:50 at Manchester. The further finding of subclinical oxidative stress in Sowetan controls and the endemic nature of chronic pancreatitis in that area supports the hypothesis that oxidative stress may be involved in its pathogenesis.

Topics: Adult; Ascorbic Acid; Biomarkers; Black People; Chromatography, High Pressure Liquid; Chronic Disease; Cohort Studies; England; Female; Free Radicals; Humans; Lipid Peroxides; Male; Middle Aged; Oxidative Stress; Pancreatitis; Reference Values; South Africa; Urban Population

Severe acute pancreatitis (SAP) is a necrotic pancreatic inflammation associated with high mortality rate (up to 70%). Bone marrow (BM) mesenchymal stem cells (MSCs) have been investigated in pancreatic cellular regeneration, but still their effects are controversial. Therefore, the present study is aimed at examining the enrichment of the stem cells with ascorbic acid (AA) and N-acetylcysteine (NAC) and explore their combined action on the expression of the inflammatory cytokines: interleukin 1

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Body Weight; Caspase 3; Cell Proliferation; Ceruletide; Fluorescent Dyes; Insulin; Interleukin-1beta; Islets of Langerhans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; NF-kappa B; Organic Chemicals; Pancreatitis; Proliferating Cell Nuclear Antigen; Rats; Regeneration; Tumor Necrosis Factor-alpha

To observe the changes of renal function in critically ill patients using vancomycin and analyze the renal protective effect of high dose vitamin C (VC) on vancomycin nephrotoxicity.. Retrospective analysis was carried out to enroll the patients who were hospitalized in emergency intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to October 2019. All patients were administered with vancomycin or VC infusion in addition. According to the infusion of vancomycin alone or in combination with VC, the patients were divided into vancomycin group and vancomycin in combination with VC group; vancomycin group was further divided into two groups according to before vancomycin or after vancomycin usage; combination group were further divided into two groups according to before VC use or after VC. The initial dosage of vancomycin was calculated according to the actual weight of the patient and adjusted according to the renal function. The dosage of VC was determined according to the disease severity of the patient, and the dosage range was 50-200 mg×kg. The incidence of drug-induced renal injury caused by vancomycin is high. Intravenous high dose VC can significantly reduce the nephrotoxicity of vancomycin and shorten the length of hospital stay. When vancomycin is used in critically ill patients, VC can be used in combination to reduce or avoid drug-induced renal injury, improve curative effect and reduce toxic effects.

Topics: Acute Disease; Ascorbic Acid; China; Critical Illness; Humans; Neurotoxicity Syndromes; Pancreatitis; Retrospective Studies; Vancomycin

The prognosis of acute pancreatitis (AP) depends upon the degree of pancreatic necrosis and the intensity of multisystem organ failure. The liver contributes to the systemic manifestations of AP by releasing some cytokines. This study was undertaken to examine comparative effects of melatonin, antioxidant mixture containing L(+)-ascorbic acid and N-acetyl cysteine, pentoxifylline and L-arginine on hepatic damage induced by caerulein-pancreatitis.. The liver specimens of all groups showed histopathological alterations such as hepatocyte necrosis, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration. TEM studies revealed vacuole formation, mitochondrial degeneration, lysosome accumulation and necrosis. The mean histopathological score of the caerulein group was significantly different from that of each treatment group.. L-Arginine and antioxidant administration be important for reducing hepatic damage induced by AP. Improvement of hepatic damage, in turn, might be beneficial for the prognosis of AP.

Topics: Acetylcysteine; Acute Disease; Animals; Antioxidants; Arginine; Ascorbic Acid; Ceruletide; Female; Liver Diseases; Melatonin; Pancreatitis; Pentoxifylline; Rats; Rats, Wistar; Statistics, Nonparametric

To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis and associated liver injury in rats.. Thirty-eight female Wistar rats were used. Acute pancreatitis (AP) was induced by two i.p. injections of caerulein at 2-h intervals (at a total dose of 100 microg/kg b.wt). The other two groups received additional melatonin (20 mg/kg b.wt) or an antioxidant mixture containing L(+)-ascorbic acid (14.3 mg/kb.wt.) and N-acetyl cysteine (181 mg/kg b.wt.) i.p. shortly before each injection of caerulein. The rats were sacrificed by decapitation 12 h after the last injection of caerulein. Pancreatic and hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde (MDA) and changes in tissue antioxidant enzyme levels, catalase (CAT) and glutathione peroxidase (GPx). Histopathological examination was performed using scoring systems.. The degree of hepatic cell degeneration, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration showed a significant difference between caerulein and caerulein + melatonin (P = 0.001), and careulein and caerulein + L(+)-ascorbic acid + N-acetyl cysteine groups (P = 0.002). The degree of aciner cell degeneration, pancreatic edema, intracellular vacuolization and inflammatory infiltration showed a significant difference between caerulein and caerulein + melatonin (P = 0.004), and careulein and caerulein + L(+)-ascorbic acid + N-acetyl cysteine groups (P = 0.002). Caerulein-induced pancreatic and liver damage was accompanied with a significant increase in tissue MDA levels (P = 0.01, P = 0.003, respectively) whereas a significant decrease in CAT (P = 0.002, P = 0.003, respectively) and GPx activities (P = 0.002, P = 0.03, respectively). Melatonin and L(+)-ascorbic acid+N-acetyl cysteine administration significantly decreased MDA levels in pancreas (P=0.03, P=0.002, respectively) and liver (P = 0.007, P = 0.01, respectively). Administration of these agents increased pancreatic and hepatic CAT and GPx activities. Melatonin significantly increased pancreatic and hepatic CAT (P = 0.002, P = 0.001, respectively) and GPx activities (P = 0.002, P = 0.001). Additionally, L(+)-ascorbic acid + N-acetyl cysteine significantly increased pancreatic GPx (P = 0.002) and hepatic CAT and GPx activities (P = 0.001, P = 0.007, respectively).. Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage. Antioxidant agents such as melatonin and ascorbic acid + N-acetyl cysteine, are capable of limiting pancreatic and hepatic damage produced during AP via restoring tissue antioxidant enzyme activities.

Topics: Acetylcysteine; Acute Disease; Animals; Antioxidants; Ascorbic Acid; Ceruletide; Female; Lipid Peroxidation; Liver; Melatonin; Pancreatitis; Rats; Rats, Wistar; Reactive Oxygen Species

The aim of this study was to establish the main determinants of plasma antioxidant potential in different types of human pancreatitis: chronic pancreatitis (CP, n = 19), chronic pancreatitis exacerbated (CPE, n = 16), and acute pancreatitis (AP, n = 8).. We measured the plasma thiobarbituric acid reactive substances (TBARS), total peroxyl radical trapping potential (TRAP), and the levels of antioxidants such as uric acid (UA), SH groups (SH), ascorbic acid (AA), and bilirubin (BIL).. In comparison to healthy volunteers (HV, n = 22) the average levels of TBARS in all types of pancreatitis were significantly higher (by 50%-90%), and plasma SH groups were lower (approximately 30%). In the multivariate regression models, the variability of plasma TRAP was explained in the HV group through UA only (36%), in the CP group through UA, AA, and BIL together (75%), and in CPE group through UA and AA together (81%). Plasma SH concentration did not enter the regression models in all groups. The AP group revealed "paradoxically" high concentrations of AA and TRAP and a negative, linear correlation between the level of TRAP versus UA concentration (R = -0.87).. The multivariate regression analysis points to different structures of antioxidant defense in healthy people and those with pancreatitis: they were much the same in the CP and CPE groups but fundamentally different in the AP group. AP may activate unidentified antioxidant defenses as an adaptive response against oxidative stress.

Topics: Acute Disease; Adult; Aged; Antioxidants; Ascorbic Acid; Bilirubin; Chronic Disease; Humans; Middle Aged; Multivariate Analysis; Oxidative Stress; Pancreatitis; Reference Values; Regression Analysis; Thiobarbituric Acid Reactive Substances; Uric Acid

Oxygen free radicals (OFR) have been implicated in the induction of acute pancreatitis (AP).. The aim of this study was to determine the effect of ascorbic acid and N-acetylcysteine (NAC), potent antioxidants, against oxidative stress in AP.. AP was induced by two i.p. injections of caerulein at 2-hour intervals (50 microg/kg BW). One group received additionally an antioxidant mixture composed of L(+)-ascorbic acid (14.3 mg/kg BW) and NAC (181 mg/kg BW) i.p. The rats were sacrificed 12 h after the last injection. Oxidative stress markers were evaluated. Light-microscopic and ultrastructural examination was performed.. Formation of vacuoles, mitochondrial damage, and dilatation of rough endoplasmic reticulum, margination and clumping of chromatin were major ultrastructural alterations in AP group. Ascorbic acid + NAC prevented these changes. Small vacuoles were present within the cytoplasm of some of the acinar cells. Pancreas damage was accompanied by an increase in tissue malondialdehyde (MDA) levels (p < 0.05), whereas a decrease was seen in catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities and total glutathione (GSH) levels (p < 0.005). Ascorbic acid + NAC decreased MDA levels but increased CAT, SOD, GPx activities and GSH levels (p < 0.005).. These results suggest that ascorbic acid + NAC is potentially capable of limiting pancreatic damage produced during AP via protecting fine structure of acinar cells and tissue antioxidant enzyme activities.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Ceruletide; Female; Gastrointestinal Agents; Oxidative Stress; Pancreas; Pancreatitis; Rats; Rats, Sprague-Dawley

Patients with chronic pancreatitis (CP) are at high risk of antioxidant deficiencies. Furthermore, this disease can lead to diabetes mellitus (DM) that could exacerbate the severity of oxidative stress. Oxidative stress and the resulting LDL oxidation are a major cause of atherosclerosis.. The objective of the study was to ascertain whether diabetes significantly modifies oxidative status in patients with CP.. CP patients with or without DM were compared with type 1 DM patients and healthy control subjects.. Two-way factorial analyses showed that a decrease in the plasma concentrations of vitamin A, vitamin E, and carotenoids accompanied both CP and DM, and CP was also associated with lower plasma concentrations of selenium and zinc, lower catalase activity, and higher plasma concentrations of copper. The lag phase of LDL oxidation was lower in CP patients with or without DM than in the control subjects, whereas there was no significant difference between type 1 DM patients and control subjects. Multivariate analysis showed that LDL vitamin E (R2 = 0.24, P < 0.0001) and fasting plasma glucose (R2 = 0.32, P < 0.0001) concentrations were the main determinants of the lag phase of LDL oxidation.. Antioxidant status is altered in CP patients, particularly in those who also have DM. In these patients, a vitamin E deficiency and an elevated plasma glucose concentration were associated with significantly higher LDL oxidizability.

Topics: Adult; Antioxidants; Ascorbic Acid; Blood Glucose; Body Mass Index; Case-Control Studies; Chronic Disease; Diabetes Mellitus; Humans; Male; Middle Aged; Oxidative Stress; Pancreatitis; Selenium; Vitamin A; Vitamin E; Zinc

Oxidative stress mediates acinar injury in experimental acute pancreatitis (AP) and antioxidants are depleted in human AP. This study tests the hypothesis that exogenous antioxidant supplementation ameliorates experimental AP.. Male Sprague-Dawley rats were randomly allocated to 1 of 4 groups (n = 5/group) and sacrificed at 72 h. AP was induced by 250 mg per 100 g body weight of 20% L-arginine hydrochloride in 0.15 mol/l sodium chloride. Group allocations were: group 1 (control) no intervention; group 2 AP; group 3 early multiple antioxidant (MAOX) intervention comprising 15 microg/kg selenium, 30 microg/kg ascorbate and 300 mg/kg N-acetylcysteine given at 6 and 30 h and group 4 the MAOX combination above given at 24 and 48 h. Endpoints were: serum amylase, antioxidant levels, bronchoalveolar lavage (BAL) protein and lung myeloperoxidase (MPO) activity and histological assessment of pancreatic injury.. L-arginine induced AP characterised by oedema, neutrophil infiltration, acinar cell degranulation and elevated serum amylase. Early MAOX reduced pulmonary MPO and BAL protein and reduced acinar swelling, degranulation and pancreatic parenchymal infiltration by inflammatory cells. These features were absent when intervention was delayed.. In this model, early but not late antioxidant intervention ameliorates pancreatic and pulmonary injury.

Topics: Acetylcysteine; Acute Disease; Amylases; Animals; Antioxidants; Arginine; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Drug Therapy, Combination; Injections, Intravenous; Lung; Male; Pancreas; Pancreatitis; Peroxidase; Proteins; Rats; Rats, Sprague-Dawley; Selenium; Time Factors

Topics: Antioxidants; Arthritis, Rheumatoid; Ascorbic Acid; Cardiovascular Diseases; Chronic Disease; Comorbidity; Diabetes Mellitus; Free Radicals; Gastritis; Inflammation; Oxidation-Reduction; Oxidative Stress; Pancreatitis

Reactive oxygen species have been implicated in the pathogenesis of acute pancreatitis. Few studies have focused on the loss of endogenous antioxidants and molecular oxidative damage. Two acute pancreatitis models in rats; taurocholate (3% intraductal infusion) and cerulein (10 microg/kg/h), were used to study markers of oxidative stress: Glutathione, ascorbic acid, and their oxidized forms (glutathione disulfide and dehydroascorbic acid), malondialdehyde, and 4-hydroxynoneal in plasma and pancreas, as well as 7-hydro-8-oxo-2'-deoxyguanosine in pancreas. In both models, pancreatic glutathione depleted by 36-46% and pancreatic ascorbic acid depleted by 36-40% (p <.05). In the taurocholate model, plasma glutathione was depleted by 34% (p <.05), but there were no significant changes in plasma ascorbic acid or in plasma and pancreas dehydroascorbic acid, malondialdehyde, and 4-hydroxynoneal, and no significant changes in the pancreas glutathione disulfide/glutathione ratio. While pancreas glutathione disulfide/glutathione ratio increased in the cerulein model, there were no significant changes in plasma glutathione, plasma, or pancreas ascorbic acid, dehydroascorbic acid, 4-hydroxynoneal, and malondialdehyde, or in pancreas 7-hydro-8-oxo-2'-deoxyguanosine. Reactive oxygen species have a minor role in the intermediate stages of pancreatitis models.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acute Disease; Aldehydes; Animals; Ascorbic Acid; Biomarkers; Ceruletide; Dehydroascorbic Acid; Deoxyguanosine; Glutathione; Glutathione Disulfide; Male; Malondialdehyde; Oxidation-Reduction; Oxidative Stress; Pancreatitis; Rats; Rats, Wistar; Reactive Oxygen Species; Taurocholic Acid

Ascorbic acid (AA) is an important endogenous antioxidant in plasma and has been shown to be decreased at the time of hospital admission in patients with acute pancreatitis. The aim of this study was to determine whether plasma AA concentration continues to decrease after admission and whether the extent of decrease is related to the severity of pancreatitis.. Consecutive patients with mild (n = 62) and severe (n = 23) acute pancreatitis had plasma AA concentration measured on the day of recruitment and on days 2 and 5 by high-performance liquid chromatography.. The plasma AA concentration in patients with acute pancreatitis was significantly less than that in normal volunteers on days 0, 2 and 5 (P < 0.0001) and this was more marked in those with severe disease. There was a decrease in plasma AA concentration from day 0 to day 2 in patients with mild (P < 0.0001) and severe (P = 0.0005) pancreatitis, and from day 2 to day 5 in patients with severe pancreatitis (P = 0.023).. Endogenous plasma AA continues to decrease over the first 5 days in hospital and the extent is related to the severity of acute pancreatitis. Presented to a meeting of the Australasian Surgical Research Society, Auckland, New Zealand, August 1995 and published in abstract form as Aust N Z J Surg 1996; 66: 243

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Biomarkers; Female; Humans; Male; Middle Aged; Pancreatitis; Time Factors; Treatment Outcome

In patients with an acute destructive pancreatitis the lowering of sulphhydride (SH) groups in proteinic and nonproteinic fraction of the blood plasma, the reduction of the ascorbic acid level and increase of its oxidized forms concentration was noted. After the operation the disordered indexes have restored, moreover, and after the programmed relaparotomy conduction--as after a single operative intervention. Acceleration of the disordered indexes restoration was promoted by application of pentoxifylline and low-intensity laser irradiation as well.

Topics: Acute Disease; Adult; Ascorbic Acid; Combined Modality Therapy; Disulfides; Female; Humans; Infrared Rays; Laser Therapy; Male; Middle Aged; Oxidation-Reduction; Pancreatectomy; Pancreatitis; Pentoxifylline; Phosphodiesterase Inhibitors; Sulfhydryl Compounds

Reactive oxygen species and related oxidative damage have been implicated in the initiation of acute pancreatitis. Changes in these parameters during disease progression merit further investigation.. To evaluate changes and the clinical relevance of superoxide radicals, endogenous antioxidants, and lipid peroxidation during the course of acute pancreatitis.. Superoxide radicals (measured as lucigenin amplified chemiluminescence), ascorbic acid, dehydroascorbic acid, alpha tocopherol, and lipid peroxidation (measured as thiobarbiturate reactive substances) were analysed in blood samples from 56 healthy subjects, 30 patients with mild acute pancreatitis, and 23 patients with severe acute pancreatitis. The association with grades of disease severity was analysed. Measurements were repeated one and two weeks after onset of pancreatitis.. In the blood from patients with acute pancreatitis, there were increased levels of the superoxide radical as well as lipid peroxides. There was notable depletion of ascorbic acid and an increased fraction of dehydroascorbic acid. Changes in alpha tocopherol were not great except in one case with poor prognosis. Differences between severe and mild acute pancreatitis were significant (p < 0.01). Variable but significant correlations with disease severity scores were found for most of these markers. The normalisation of these indexes postdated clinical recovery one or two weeks after onset of disease.. Heightened oxidative stress appears early in the course of acute pancreatitis and lasts longer than the clinical manifestations. The dependence of disease severity on the imbalance between oxidants and natural defences suggests that oxidative stress may have a pivotal role in the progression of pancreatitis and may provide a target for treatment.

Topics: Acute Disease; Antioxidants; Ascorbic Acid; Female; Humans; Lipid Peroxidation; Luminescent Measurements; Male; Middle Aged; Oxidative Stress; Pancreatitis; Statistics, Nonparametric; Superoxides; Thiobarbituric Acid Reactive Substances; Vitamin E

Recent evidence has suggested that ischemia-reperfusion injury is fundamental to the pathogenesis of acute pancreatitis. This study was designed to determine whether acute pancreatitis is associated with elevated serum manganese superoxide dismutase (MnSOD), a key antioxidant enzyme, considered a marker of ischemia-reperfusion injury in myocardial infarction. Thirty-four patients with acute pancreatitis had measurements of MnSOD on days 0, 2, and 5 after recruitment. The patients were recruited within 12 h of admission to hospital and had measurements of MnSOD on days 0, 2, and 5. Patients with severe acute pancreatitis had significantly elevated serum MnSOD concentrations on days 2 and 5 compared with patients with mild acute pancreatitis, but not on the day of recruitment. Elevated serum MnSOD correlated with peripheral plasma markers of lipid peroxidation (malondialdehyde) and neutrophil activation (myeloperoxidase) and was associated with decreased plasma ascorbic acid concentrations. The serial measurement of serum MnSOD may prove useful as a marker of the effectiveness of treatment designed to limit ischemia-reperfusion injury in patients with severe acute pancreatitis.

Topics: Acute Disease; Adult; Aged; Ascorbic Acid; Biomarkers; C-Reactive Protein; Female; Humans; Male; Malondialdehyde; Middle Aged; Pancreatitis; Peroxidase; Reperfusion Injury; Superoxide Dismutase

Vitamin C can be used to overcome oxidative stress and ease pain in chronic pancreatitis. But its use is deprecated in conditions of tissue iron overload, because its bioactive form, ascorbate, can accelerate free-radical reactions that are driven by transition metals. We measured iron, ascorbate and copper in Sowetan Blacks (RSA) with chronic pancreatitis, obtaining serum/plasma from 14 consecutive patients and 15 controls. Compared with data from corresponding groups in Manchester, African samples had less ascorbate (p < 0.0001), but more caeruloplasmin (p < 0.0001). African and British controls had comparable iron and iron-binding capacity. Plasma from African patients had less ascorbate than that from African controls (p < 0.005) and in six samples, ferritin exceeded 300 micrograms/l (677 pmol/l). Low-molecular-mass iron or copper, capable of participating in free radical reactions, was not detected. British patients, had similar caeruloplasmin levels to African patients but higher ascorbate levels. There is no evidence of iron overload in our African samples. Outwardly healthy controls from Soweto have elevated levels of caeruloplasmin, possibly to compensate for dietary deficiency of ascorbate. Persistent oxidative stress is a unifying feature of chronic pancreatitis, but its degree is higher in African than British patients. Supplements of vitamin C should be safe in Blacks of southern Africa.

Topics: Adult; Aged; Ascorbic Acid; Case-Control Studies; Ceruloplasmin; Chronic Disease; Copper; Female; Humans; Iron; Male; Middle Aged; Pancreatitis; South Africa

Biochemical assessments of micronutrient antioxidant status were done in 14 consecutive black patients with calcific chronic pancreatitis and 15 controls at Soweto, near Johannesburg in southern Africa. The patients showed subnormal levels of vitamin C in plasma; selenium, beta-carotene and alpha-tocopherol in serum; and inorganic sulphate (as an index of long-term sulphur amino acid intake) in urine (P < 0.001 for each): furthermore, among the patients ascorbate constituted a lower fraction of vitamin C (P < 0.002), indicating heightened oxidation of the bioactive form. By comparing the results in Sowetan controls with reference ranges from Manchester, UK, the markedly lower vitamin C and, hence, ascorbate levels in the Sowetans was underlined (P < 0.001) and their selenium levels were also lower (P < 0.001), but beta-carotene, alpha-tocopherol and inorganic sulphate levels were comparable. The very low bioavailability of ascorbate among Sowetan controls is reminiscent of our previous finding in outwardly healthy people at Madras in southern India: in both these areas chronic pancreatitis is currently endemic, has a propensity to pancreatic calculi and runs a virulent course towards premature death from diabetes, malnutrition or pancreatic cancer. Considering that low ascorbate levels are a feature in patients with chronic pancreatitis who develop pancreatic calculi at Manchester and that antioxidant supplements ameliorate painful symptoms, we suggest that poor antioxidant intake may predispose underprivileged tropical communities to the disease. If so, there could be an opportunity for prophylaxis through a daily tablet containing vitamin C, perhaps along with selenium at Soweto and beta-carotene at Madras.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Black People; Carotenoids; Chronic Disease; Female; Humans; Male; Micronutrients; Middle Aged; Pancreatitis; Reference Values; Selenium; South Africa; Sulfates; Vitamin E

Vitamin C is a key antioxidant in human blood plasma and hence could influence the outcome of conditions such as acute pancreatitis in which oxidative stress apparently plays a pivotal role. The concentrations of vitamin C and its immediately bioavailable form, ascorbic acid, in fasting plasma samples from 30 healthy volunteers were compared with those in admission samples from 29 consecutive patients with acute pancreatitis and 27 patients with other acute abdominal crises. Median (range) levels of vitamin C and ascorbic acid, respectively, were 15 (6.3-19) and 12 (4.5-18) micrograms/ml in the control group, 2.8 (0.3-10) and < 0.5 (< 0.5-6.0) micrograms/ml in patients with acute pancreatitis, and 3.7 (0.6-15) and 2.3 (< 0.5-15) micrograms/ml in those with other acute abdominal problems. Admission plasma samples showed equally low vitamin C levels in both groups of patients (P < 0.001 versus controls), but those from patients with acute pancreatitis were further characterized by a disproportionate reduction in ascorbic acid, such that the concentration of ascorbic acid and its ratio to vitamin C were both significantly lower than in samples from patients with an acute abdomen (P < 0.005 and P < 0.001 respectively). It is concluded that the stress of an acute intra-abdominal crisis is accompanied by a non-specific decrease in the plasma level of vitamin C. In acute pancreatitis early and profound oxidative stress compounds this problem by denaturing the available vitamin. There may be a case for the judicious parenteral administration of ascorbic acid to patients with acute pancreatitis to boost plasma antioxidant defence.

Topics: Abdomen, Acute; Acute Disease; Adult; Ascorbic Acid; Follow-Up Studies; Humans; Middle Aged; Pancreatitis; Reference Values; Regression Analysis

To define the role of free radicals and of lipid peroxide involvement during the progress of cerulein-induced acute pancreatitis in mice, we evaluated the effect of a novel free radical scavenger, 2-octadecylascorbic acid (CV-3611), on pancreatic edema formation, and the levels of serum enzymes (amylase, lipase) and of lipid peroxide in pancreatic tissue. Mice were divided into three groups: control group, intraperitoneal injection of saline only; pancreatitis group, cerulein 50 micrograms/kg injected intraperitoneally six times at 1-hr intervals; treatment groups, CV-3611 10 mg/kg subcutaneously just after intraperitoneal cerulein injection. After the cerulein injection, the degree of pancreatic edema formation, serum amylase and lipase levels, and the amount of lipid peroxide in pancreatic tissue increased significantly during the observation period of 12 hr. Treatment with CV-3611 resulted in significant reduction in pancreatic edema formation at 3.5 hr (P less than 0.05) and 9 hr (P less than 0.05), serum amylase and lipase levels at 3.5 hr (P less than 0.05) and 12 hr (P less than 0.05), and lipid peroxide levels at 3.5 hr (P less than 0.05), 6 hr (P less than 0.05) and 12 hr (P less than 0.05). These results indicate that a novel free radical scavenger, CV-3611, has a strong therapeutic effect during the development of acute pancreatitis and suggest that oxygen-derived free radicals play an important role in the pathogenesis of acute pancreatitis.

Topics: Acute Disease; Amylases; Animals; Ascorbic Acid; Ceruletide; Female; Free Radical Scavengers; Lipase; Mice; Mice, Inbred BALB C; Pancreatitis; Peroxidases

The therapeutic effects of CV 3611, a new synthetic free radical scavenger prepared from an ascorbic acid derivative, on choline deficient, ethionine enriched (CDE) diet induced acute pancreatitis in mice were evaluated and compared with those of superoxide dismutase. Time/course studies after subcutaneous injection of CV 3611 in normal mice showed a peak plasma concentration of mean (SEM) 0.54 (0.09) micrograms/ml at one hour, with a gradual decrease over the next 10 hours, while a peak concentration in pancreatic tissue of mean (SEM) 425 (33) ng/g tissue was achieved at three hours and the drug was undetectable at 12 hours. Survival rates and activities of pancreatic enzymes (amylase, lipase, elastase I) were compared in control mice and animals that received CV 3611 before or at the time of feeding the CDE diet. The survival rate was observed in a no treatment group and mice given pretreatment or treatment with CV 3611 or superoxide dismutase. The survival rate was significantly better in the treatment group given CV 3611 (p less than 0.02), but superoxide dismutase had no significant effect on survival. The increases in the three serum enzyme activities were significantly less at 48 hours in the groups given pretreatment or treatment with CV 3611 than in the no treatment group. These results indicate that CV 3611, which has been proved to pass through the cell membrane and to have a long half life in plasma and tissue, had an important therapeutic effect on the development of acute pancreatitis. They also suggest that oxygen derived free radicals may play an important role in the development of acute pancreatitis.

Topics: Amylases; Animals; Ascorbic Acid; Ethionine; Female; Free Radical Scavengers; Lipase; Mice; Mice, Inbred BALB C; Pancreas; Pancreatic Elastase; Pancreatitis

In order to clarify the role of free radicals in the pathogenesis of acute pancreatitis, we observed the effect of a new synthetic free radical scavenger (CV-3611) on the pathological state in the models of both caerulein and CDE-diet induced acute pancreatitis in mice. In both models of acute pancreatitis, the levels of serum amylase activity were reduced significantly by the treatment of CV-3611. Pancreatic edema formation was also reduced significantly at 3.5 and 9 h after the first caerulein i.p. injection. The 4 days survival rate in CDE-diet induced pancreatitis was significantly elevated from 41.2% to 81.3% by the treatment of CV-3611. These results indicate that this synthetic scavenger, which has a long circulation half life, high affinity to biomembrane and good cell penetration ability, is effective on the development of both severe and mild pancreatitis. The main pathogenesis of both models is suggested to be radical reactions on the biomembrane which is caused by the interreaction between endothelium and neurophile in caerulein induced pancreatitis, and by the lipid peroxidation on the biomembrane of the organella in the cell in CDE-diet induced pancreatitis.

Topics: Acute Disease; Amylases; Animals; Ascorbic Acid; Ceruletide; Endothelium; Ethionine; Female; Free Radicals; Lipid Peroxidation; Mice; Mice, Inbred BALB C; Neutrophils; Pancreatitis

Topics: Ascorbic Acid; Blood Chemical Analysis; Chromatography, High Pressure Liquid; Dehydroascorbic Acid; Humans; Pancreatitis

Fifteen patients with idiopathic chronic pancreatitis (aged 17-78 years), who had not altered their diet since their first symptoms, completed 7-d weighed dietary records at home. The computed information was compared with that from 15 age- and sex-matched volunteers. Attention was focussed on the intakes of antioxidants and unsaturated fatty acids. The patients ingested less selenium, vitamin E, vitamin C and riboflavin than did controls (P less than 0.001, P less than 0.02, P less than 0.001 and P less than 0.05 respectively, using paired t-tests): selenium was by far the best discriminator on step-wise analysis. When the selenium intakes were examined alongside the results of theophylline tests--which reflect cytochromes P450 activities and, thereby, provide an index of antioxidant demand--a line of discrimination separated the majority of patients (with faster drug clearances and lower selenium intakes) and controls. There were no differences in the intakes of individual unsaturated fatty acids, C14:1 through to C24:6, between the two groups. However, amongst six subjects in the overlap zone, three with chronic pancreatitis habitually ate greater amounts of highly unsaturated fatty acids C20:4 to C24:6 inclusive (1970, 1049, 750 mg/d) than did three controls (329, 320, 82 mg/d). Animal experiments show that suboptimal intakes of dietary antioxidants and/or excessive intakes of highly unsaturated fatty acids and/or induction of cytochromes P450 facilitate peroxidation of cellular lipid membranes by free radicals. Our dietary data, taken in conjunction with pharmacokinetic data, thus suggest that a similar situation--favouring lipid peroxidation--may underlie human chronic pancreatitis.

Topics: Adolescent; Adult; Aged; Antioxidants; Ascorbic Acid; Chronic Disease; Cytochrome P-450 Enzyme System; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Enzyme Induction; Fatty Acids, Unsaturated; Female; Humans; Lipid Peroxides; Male; Middle Aged; Pancreatitis; Riboflavin; Selenium; Vitamin E

Topics: Adult; Ascorbic Acid; Female; Hepatitis; Humans; Male; Middle Aged; Pancreatitis; Peptic Ulcer; Thiamine

Topics: Anesthesia, Conduction; Ascorbic Acid; Blood Protein Disorders; Chronic Disease; Humans; Hydrocortisone; Injections, Intravenous; Injections, Subcutaneous; Lipotropic Agents; Methionine; Pancreatic Extracts; Pancreatin; Pancreatitis; Pituitary Hormones, Posterior; Plasma Substitutes; Prednisolone; Procaine; Protein Hydrolysates; Serine; Serum Albumin; Serum Globulins; Strychnine; Thiamine; Water-Electrolyte Balance

Topics: Aged; Anti-Bacterial Agents; Ascorbic Acid; Humans; Indomethacin; Liver Function Tests; Male; Pancreatitis; Parasympatholytics; Vitamin B Complex