Antioxidant value and element content in some tinctures used in medication.

Tinctures are almost the oldest medicines and their use is substantial in the medication nowadays as well. The antioxidant values by ferric reducing/antioxidant power (FRAP) method and element content by inductively coupled plasma optical emission spectrometry (ICP-OES) were investigated in some tinctures official in the VII. and VIII. Pharmacopoeia Hungarica. The highest FRAP values were found for volatile oil containing Tinctura Aurantii amari epicarpii et mesocarpii, Tinctura Amara and Tinctura Valerianae (764.54 ± 19.90; 757.37 ± 14.46; 826.40 ± 5.89 µmol l⁻¹, respectively). The correlations between the FRAP values and dilution with different alcohol content in Tinctura Chinae, Tinctura Ipecacuanhae normata and Tinctura Strychni were also investigated. Remarkable differences were found between the element concentrations in the different tinctures. The element contents in tinctures are not so high in absolute values nevertheless the presence of essential selenium, zinc, manganese and copper is important since they have key role in the antioxidant system. The common feature of the tinctures seems to be the lithium content. The Ca to Mg concentration ratio was found to be shifted towards magnesium in some of the tinctures that can show a higher Mg absorption which could affect against the proinflammatoric processes in the cases of gastrointestinal diseases.

Different administration schedules of darbepoetin alfa affect oxidized and reduced glutathione levels to a similar extent in 5/6 nephrectomized rats.

BACKGROUND: The development of erythropoiesis-stimulating agents (ESAs) with extended serum half-lives has allowed marked prolongation of the administration intervals. The level of oxidative stress is increased in chronic kidney disease, and is reportedly decreased after long-term ESA treatment. However, the effect of different dosing regimens of ESAs on oxidative stress has not been elucidated. METHODS: Five-sixths nephrectomized (NX) rats received either 0.4 µg/kg darbepoetin alfa (DA) weekly or 0.8 µg/kg DA fortnightly between weeks 4 and 10. NX animals receiving saline and a sham-operated (SHAM) group served as controls. The levels of oxidized and reduced glutathione (GSSG, GSH) were followed from blood samples drawn fortnightly. RESULTS: During the follow-up, the ratios GSSG/GSH showed similar trends in both DA groups, levels being significantly lower than those in the SHAM group at weeks 8 and 10. GSSG levels were lower than the baseline throughout the study in all groups except for NX controls. The GSH levels were increased in all three NX groups (weeks 6-10) compared with both the baseline and the SHAM group CONCLUSION: Our results suggest that the extent of oxidative stress is similar in response to different dosing regimens of DA in 5/6 NX rats when comparable hemoglobin levels are maintained. These findings remain to be confirmed in chronic kidney disease patients.

Blood lipid peroxidation, antioxidant enzyme activities and hemorheological changes in autistic children.

OBJECTIVES: Early infantile autism is a severe form of childhood psychiatric disease with characteristic symptoms. Hyperserotoninaemia in 43.5%, lactic acidosis 43% and hyperpyruvataemia in 30% were biochemically demonstrated in autistic children. Our earlier results led to the postulation that a dissequilibrium in the blood redox is involved in infantile autism; the oxidative loading and the antioxidant defending enzyme system were investigated together with the hemorheological parameters in infantile autism. METHODS: Malonyl-dialdehyde (MDA) endproduct of lipid peroxidation and activities of the antioxidant enzymes: superoxide dismutase (SOD), catalase (C-ase), glutathione peroxidase (GP-ase) and reduced glutathione (GSH) were biochemically determined from plasma and red blood cells. PATIENTS: The antioxidant specificities were investigated in plasma and red blood cell haemolysate from 25 infantile autistic children. RESULTS: Significantly increased superoxide dismutase (SOD) (2.89 vs. 1.32 U/mg protein, p < 0.01) and decreased glutathione peroxidase (0.620 vs. 0.910 U/mg protein, p < 0.01) levels as well as catalase (0.463 vs. 4.948 BU/mg protein, p < 0.001) activities were detected; while the plasma and erythrocyte lipid peroxidation and the reduced glutathione (GSH) levels did not change. The results of the investigated prooxidant and the antioxidant status provide evidence that there exists an oxidative stress in children with infantile autism. While investigating the hemorheological parameters of 25 infantile autistic patients, some characteristic pathological parameters were detected: the initial filtration rate (Fi) (0.72 vs. 0.75 p < 0.01) and the clogging rate (CR) (1.926 vs. 2.912, p < 0.01) values of red blood cells (RBC) decreased while the mean transit time (Tc) (8.93 vs. 7.39, p < 0.001) increased suggesting reduced RBC deformability.

Expression analysis of heat shock genes in the skin, spleen and blood of common carp (Cyprinus carpio) after cadmium exposure and hypothermia.

Heat shock proteins are chaperones that play a pivotal role in controling multiple regulatory pathways such as stress defense, hormone signaling, cell cycle control, cell proliferation and differentiation, and apoptosis. In this study, the expression patterns of four well-known heat shock genes (hsp70, hsc70-1, hsc70-2 and hsp90α) were characterized in the skin, spleen and blood cells of the common carp, under unstressed conditions and after Cd2+ treatment or hypothermia. The examined genes were expressed in a tissue-specific manner: hsc70-2 was expressed constitutively, and was at best only slightly inducible; hsp90α exhibited a high basic expression in all three tissues, whereas hsc70-1 did so only in the blood cells, the expression of hsp70 proved to be below the level of detection in unstressed fish. Cold shock induced the expression of hsp genes in the spleen (hsp90α) and blood cells (hsp70, hsc70-1 and hsp90α), while Cd2+ treatment has no effect on the expression pattern. The highest inducibilities were detected in the skin: for hsp70 an induction of at least 20-fold after cadmium exposure, for hsc70-1 of at least 30-fold and for hsp90α of 3-fold after hypothermia.

Microvascular reactivity in lean, overweight, and obese hypertensive adolescents.

UNLABELLED: The microvascular responses to endothelium-dependent vasodilators (e.g., acetylcholine), endothelium-independent vasodilators (e.g., sodium nitroprusside), and to local heating were studied (for the first time) in adolescents with essential hypertension, grouped according to their body mass index. The forearm microvascular reactivities of thirty-three hypertensive adolescents (ten lean, 13 overweight, and ten obese) and 19 healthy controls were assessed by means of laser Doppler flowmetry. Blood levels of enzymatic and nonenzymatic antioxidants and malondialdehyde were determined. The perfusion increments in response to acetylcholine iontophoresis were not significantly attenuated in the patient groups as compared with the controls. Sodium nitroprusside (SNP) iontophoresis resulted in significantly smaller perfusion increments in the lean and obese hypertensives than in the controls (both p < 0.05). Similar responses to local heating (44°C) performed after either acetylcholine or SNP iontophoresis were observed at the respective measurement sites. As compared with the controls, we found elevated ratios of the whole blood oxidized and reduced glutathione in all the patient groups (all p < 0.001), increased erythrocyte catalase activities in the overweight hypertensives (p < 0.05), and decreased ratios of the plasma alpha-tocopherol and triglycerides in the obese hypertensive group (p < 0.05). CONCLUSION: The endothelium-dependent microvascular reactivity was not significantly attenuated in the hypertensive adolescents in contrast with the impaired endothelium-independent vasorelaxation in the lean and obese hypertensives.

Inhibition of lipid peroxidation of herbal extracts (obtained from plant drug mixtures of Myrtilli folium, Phaseoli fructus sine seminibus and Salviae folium) used in type 2 diabetes mellitus.

Plant drug mixtures are widely used in the adjuvant therapy of type 2 diabetes mellitus for the prevention of complications. The drug mixtures generally contribute to the efficiency of the therapy and may also reduce undesirable side effects. Two herbal extracts (lyophilized aqueous extracts of plant drug mixtures 1: Myrtilli folium, Phaseoli fructus sine seminibus and 2: Myrtilli folium, Phaseoli fructus sine seminibus, Salviae folium) were investigated in in vitro rat models. The content of bioactive constituents (polyphenol, flavonoid and vitamin C) in plant drug mixtures and lyophilized samples was evaluated. The antioxidant activity of lyophilized extracts was determined by measuring the ferric reducing ability of the plant, Fe2+ induced lipid peroxidation (LPO) in rat brain homogenates and NADPH (beta-nicotinamide adenine dinucleotide phosphate reduced form) induced LPO in cerebral microsomes. The antioxidant activity of lyophilized extracts was compared to that of quercetin and rutin. Both teas of lyophilized extracts had significant reducing ability (2694 and 2771 micromol/l) and inhibited LPO (IC50 28.0 and 20.6 microl in NADPH induced LPO, 17.3 and 8.7 microl in Fe2+ induced LPO). The high concentration of polyphenol/flavonoid (12.38-13.00 and 1.45-5.22 g/100 g, respectively) and vitamin C (0.099-0.165 g/100 g) in the herbal extracts is related to their significant antioxidant properties. The tea mixtures have significant nutritional value, since the consumption of 2 or 3 cups of tea a day covers 50% of the daily requirement of vitamin C and it is also relevant polyphenol source. The high polyphenol/flavonoid content may restore the redox imbalance and contribute to the prevention of diabetic complications.

Endothelial nitric oxide synthase is up-regulated in the umbilical cord in pregnancies complicated with intrauterine growth retardation.

BACKGROUND: NO and NO synthases (NOS) play an important role in the physiology of the fetomaternal blood circulation, although their expression in pathological conditions is unclear. Intrauterine growth retardation (IUGR) is a disorder most probably caused by abnormality of the fetomaternal bloodflow. MATERIALS AND METHODS: The expression of endothelial NOS (ecNOS) from arteria umbilicalis and the nitrite and peroxynitrite level of umbilical blood were determined. Major consequences of peroxynitrite toxicity are lipid peroxidation and glutathione depletion; these parameters were also measured. Finally, superoxide dismutase (SOD) activity was assayed to evaluate the level of superoxide anions. RESULTS: Elevated expression of ecNOS was found to be coupled with significantly lower SOD activity and glutathione level, and increased lipid peroxidation in IUGR neonates. CONCLUSION: The increased NO indices could represent a compensatory effort to improve placental bloodflow, but in IUGR neonates it is coupled with inadequate antioxidant defence, resulting in significant oxidative stress.

Cadmium-induced oxidative stress and antioxidative mechanisms in germinating Indian mustard (Brassica juncea L.) seeds.

Cadmium, known as a non-essential heavy metal, can cause oxidative stress in plants. In this study we tried to find out whether oxidative changes could be measured in the early stages of ontogenesis in Indian mustard (Brassica juncea L.) seeds exposed to Cd stress. Cadmium-caused oxidative stress and antioxidative responses were investigated with respect to both time- and concentration-dependence. Parameters that were measured were follows: total antioxidant capacity (ferric reducing ability of plasma (FRAP)), glutathione (GSH) content, level of lipid peroxidation (LP), total protein content, and glutathione-S-transferase (GST, EC 2.5.1.18) activity. Seeds were germinated in vitro at 0, 50, 100 and 200mg/LCd concentrations in dark for 12, 24, 48 and 96h. Oxidative stress occurred in the seeds due to Cd treatment, the level of LP was high at the beginning of the germination at all concentrations used, but it attenuated later on. FRAP showed concentration-dependent increase during 24h, but it decreased later on. GSH content was also elevated by increasing concentrations of Cd, which referred to the activity of non-enzymatic antioxidant system. The GST activity induced with germination only after 24h at the highest Cd concentration. The results show that FRAP is a suitable parameter with which to assess the antioxidant capacity of heavy metal-stressed germinating seeds.

A new severe acute necrotizing pancreatitis model induced by L-ornithine in rats.

OBJECTIVE: Intraperitoneal administration of large doses of L-arginine is known to induce severe acute pancreatitis in rats. We therefore set out to determine whether metabolites of L-arginine (L-ornithine, L-citrulline, and nitric oxide) cause pancreatitis. DESIGN: The authors conducted an in vivo animal study. SETTING: This study was conducted at a university research laboratory. SUBJECTS: Study subjects were male Wistar rats. INTERVENTIONS: Dose-response and time course changes of laboratory and histologic parameters of pancreatitis were determined after L-arginine, L-ornithine, L-citrulline, or sodium nitroprusside (nitric oxide donor) injection. MEASUREMENTS AND MAIN RESULTS: Intraperitoneal injection of 3 g/kg L-ornithine but not L-citrulline or nitroprusside caused severe acute pancreatitis; 4 to 6 g/kg L-ornithine killed the animals within hours. Serum and ascitic amylase activities were significantly increased, whereas pancreatic amylase activity was decreased after intraperitoneal injection of 3 g/kg L-ornithine. The increase in pancreatic trypsin activity (9-48 hrs) correlated with the degradation of IkappaB proteins and elevated interleukin-1beta levels. Oxidative stress in the pancreas was evident from 6 hrs; HSP72 synthesis was increased from 4 hrs after L-ornithine administration. Morphologic examination of the pancreas showed massive interstitial edema, apoptosis, and necrosis of acinar cells and infiltration of neutrophil granulocytes and monocytes 18 to 36 hrs after 3 g/kg L-ornithine injection. One month after L-ornithine injection, the pancreas appeared almost normal; the destructed parenchyma was partly replaced by fat. Equimolar administration of L-arginine resulted in lower pancreatic weight/body weight ratio, pancreatic myeloperoxidase activity, and histologic damage compared with the L-ornithine-treated group. L-ornithine levels in the blood were increased 54-fold after intraperitoneal administration of L-arginine. CONCLUSIONS: We have developed a simple, noninvasive model of acute necrotizing pancreatitis in rats by intraperitoneal injection of 3 g/kg L-ornithine. Interestingly, we found that, compared with L-arginine, L-ornithine was even more effective at inducing pancreatitis. Large doses of L-arginine produce a toxic effect on the pancreas, at least in part, through L-ornithine.

Hyperlipidemia induced by a cholesterol-rich diet aggravates necrotizing pancreatitis in rats.

The aim of the present study was to investigate whether hyperlipidemia can cause acute pancreatitis or alter its severity. Male Wistar rats were fed a 3% cholesterol-enriched diet or a normal diet for 16 weeks. Edematous and necrotizing pancreatitis was induced with 3x75 mug/kg body weight of cholecystokinin s.c. and 2x2 g/kg body weight of L-arginine i.p., respectively, in separate groups of normal and hyperlipidemic rats. The severity of the pancreatitis was assessed. We studied the influence of hyperlipidemia on the formation of oxygen-derived free radicals, endogenous scavengers, nitric oxide synthases (NOS), peroxynitrite (ONOO(-)), heat shock protein 72 (HSP72) and nuclear factor-kappa B (NF-kappaB) activation in the pancreas during acute edematous and necrotizing pancreatitis. Hyperlipidemia did not worsen edematous, but aggravated necrotizing pancreatitis. The cholesterol-enriched diet significantly reduced the catalase and Mn-superoxide dismutase (SOD) and constitutive NOS (cNOS) activities and increased the inducible NOS (iNOS) in the pancreas relative to those in the rats on the normal diet. The pancreatic nitrotyrosine level, as a marker of ONOO(-), and the NF-kappaB DNA-binding activity in the pancreas, were significantly elevated in the cholesterol-fed rats. The pancreatic HSP72 expression during necrotizing pancreatitis was not influenced by the hyperlipidemia. The pancreatic Mn-SOD, Cu, Zn-SOD, glutathione peroxidase, total glutathione and cNOS activities were significantly reduced, while the catalase, iNOS and NF-kappaB DNA-binding activities were significantly increased in the animals with necrotizing pancreatitis on the cholesterol diet as compared with those with pancreatitis and receiving the normal diet. Hyperlipidemia induced with this cholesterol-enriched diet leads to decreases in endogenous scavenger and cNOS activities, results in iNOS and NF-kappaB activation and stimulates ONOO(-) generation in the pancreas, which may be responsible for the aggravation of acute necrotizing pancreatitis.

Therapeutic proteasome inhibition in experimental acute pancreatitis.

AIM: To establish the therapeutic potential of proteasome inhibition, we examined the therapeutic effects of MG132 (Z-Leu-Leu-Leu-aldehyde) in an experimental model of acute pancreatitis. METHODS: Pancreatitis was induced in rats by two hourly intraperitoneal (ip) injections of cholecystokinin octapeptide (CCK; 2 x 100 microg/kg) and the proteasome inhibitor MG132 (10 mg/kg ip) was administered 30 min after the second CCK injection. Animals were sacrificed 4 h after the first injection of CCK. RESULTS: Administering the proteasome inhibitor MG132 (at a dose of 10 mg/kg, ip) 90 min after the onset of pancreatic inflammation induced the expression of cell-protective 72 kDa heat shock protein (HSP72) and decreased DNA-binding of nuclear factor-kappaB (NF-kappaB). Furthermore MG132 treatment resulted in milder inflammatory response and cellular damage, as revealed by improved laboratory and histological parameters of pancreatitis and associated oxidative stress. CONCLUSION: Our findings suggest that proteasome inhibition might be beneficial not only for the prevention, but also for the therapy of acute pancreatitis.

Evaluation of oxidative stress markers after vaginal delivery or Caesarean section.

BACKGROUND: The effects of vaginal delivery (VD) and of cesarean section (CS) on the markers of oxidative stress were investigated. MATERIALS AND METHODS: Umbilical blood samples were analyzed from 74 full-term neonates, 46 born via VD, 28 via elective CS. The level of lipid peroxidation (LP), protein and DNA damage and the antioxidant status were compared. RESULTS: Differences between CS and VD groups were generally non-significant for oxidative markers, except for the GSH concentrations (VD: 4.18 vs. CS: 2.77 microM/mg protein x 10(-3); p<0.05). LP was significantly higher in the CS group (0.078 vs. 0.042 nM MDA/mg protein; p <0.05). The level of carbonyl proteins was high in the VD group and significantly lower in the elective CS group (9.5 vs. 8.1 mM/mg protein x 10(-4); p<0.05). We found 0.78% more strand breaks in elective CS group than in VD group. CONCLUSION: CS does not have an advantage over VD with respect to oxidative stress.

Beneficial effect of resveratrol on cholecystokinin-induced experimental pancreatitis.

Resveratrol is a phytoalexin with strong antioxidant and anti-inflammatory effects reaching high concentrations in red wine. The aim of our study was to test the effects of resveratrol pretreatment on cholecystokinin-octapeptide (CCK-8)-induced acute pancreatitis in rats. Animals were divided into a control group, a group treated with CCK-8 and a group receiving 10 mg/kg resveratrol prior to CCK-8 administration. Resveratrol ameliorated the CCK-8-induced changes in the laboratory parameters, and reduced the histological damage in the pancreas. The drug failed to improve the pancreatic antioxidant state, but increased the amount of hepatic reduced glutathione and prevented the reduction of hepatic catalase activity. Resveratrol-induced inhibition of nuclear factor kappa B (NF-kappaB) activation or reduction of the pancreatic tumor necrosis factor-alpha (TNF-alpha) concentration could not be demonstrated. In conclusion, the beneficial effects of resveratrol on acute pancreatitis seem to be mediated by the antioxidant effect of resveratrol or by an NF-kappaB-independent anti-inflammatory mechanism.

Effect of melatonin on the severity of L-arginine-induced experimental acute pancreatitis in rats.

AIM: To determine the effect of melatonin pre- and post-treatment on the severity of L-arginine (L-Arg) -induced experimental pancreatitis in rats. METHODS: Male Wistar rats (25) were divided into five groups. Those in group A received two injections of 3.2g/kg body weight L-Arg i.p. at an interval of 1h. In group MA, the rats were treated with 50 mg/kg body weight melatonin i.p. 30 min prior to L-Arg administration. In group AM, the rats received the same dose of melatonin 1h after L-Arg was given. In group M, a single dose of melatonin was administered as described previously. In group C the control animals received physiological saline injections i.p. All rats were exsanguinated 24 h after the second L-Arg injection. RESULTS: L-Arg administration caused severe necrotizing pancreatitis confirmed by the significant elevations in the serum amylase level, the pancreatic weight/body weight ratio (pw/bw), the pancreatic IL-6 content and the myeloperoxidase activity, relative to the control values. Elevation of the serum amylase level was significantly reduced in rats given melatonin following L-Arg compared to rats injected with L-Arg only. The activities of the pancreatic antioxidant enzymes (Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase (CAT)) were significantly increased 24 h after pancreatitis induction. Melatonin given in advance of L-Arg significantly reduced the pancreatic CAT activity relative to that in the rats treated with L-Arg alone. In the liver, L-Arg significantly increased the lipid peroxidation level, and the glutathione peroxidase and Cu/Zn-SOD activities, whereas the Mn-SOD activity was reduced as compared to the control rats. Melatonin pre-treatment prevented these changes. CONCLUSION: Melatonin is an antioxidant that is able to counteract some of the L-Arg-induced changes during acute pancreatitis, and may therefore be helpful in the supportive therapy of patients with acute necrotizing pancreatitis.

The proteasome inhibitor MG132 protects against acute pancreatitis.

The cell-permeant MG132 tripeptide (Z-Leu-Leu-Leu-aldehyde) is a peptide aldehyde proteasome inhibitor that also inhibits other proteases, including calpains and cathepsins. By blocking the proteasome, this tripeptide has been shown to induce the expression of cell-protective heat shock proteins (HSPs) in vitro. Effects of MG132 were studied in an in vivo model of acute pancreatitis. Pancreatitis was induced in male Wistar rats by injecting 2 x 100 microug/kg cholecystokinin octapeptide intraperitoneally (ip) at an interval of 1 h. Pretreating the animals with 10 mg/kg MG132 ip before the induction of pancreatitis significantly inhibited IkappaB degradation and subsequent activation of nuclear factor-kappaB (NF-kappaB). MG132 also increased HSP72 expression. Induction of HSP72 and inhibition of NF-kappaB improved parameters of acute pancreatitis. Thus MG132 significantly decreased serum amylase, pancreatic weight/body weight ratio, pancreatic myeloperoxidase activity, proinflammatory cytokine concentrations, and the expression of pancreatitis-associated protein. Parameters of oxidative stress (GSH, MDA, SOD, etc.) were improved in both the serum and the pancreas. Histopathological examinations revealed that pancreatic specimens of animals pretreated with the peptide demonstrated milder edema, cellular damage, and inflammatory activity. Our findings show that simultaneous inhibition of calpains, cathepsins, and the proteasome with MG132 prevents the onset of acute pancreatitis.

A nuclear import inhibitory peptide ameliorates the severity of cholecystokinin-induced acute pancreatitis.

AIM: To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF-kappaB) inhibitor peptide PN50 in an experimental model of acute pancreatitis. PN50 was produced by conjugating the cell-penetrating penetratin peptide with the nuclear localization signal of the NF-kappaB p50 subunit. METHODS: Pancreatitis was induced in male Wistar rats by administering 2X100 mug/kg body weight of cholecystokinin-octapeptide (CCK) intraperitoneally (IP) at an interval of 1 h. PN50-treated animals received 1 mg/kg of PN50 IP 30 min before or after the CCK injections. The animals were sacrificed 4 h after the first injection of CCK. RESULTS: All the examined laboratory (the pancreatic weight/body weight ratio, serum amylase activity, pancreatic levels of TNF-alpha and IL-6, degree of lipid peroxidation, reduced glutathione levels, NF-kappaB binding activity, pancreatic and lung myeloperoxidase activity) and morphological parameters of the disease were improved before and after treatment with the PN50 peptide. According to the histological findings, PN50 protected the animals against acute pancreatitis by favoring the induction of apoptotic, as opposed to necrotic acinar cell death associated with severe acute pancreatitis. CONCLUSION: Our study implies that reversible inhibitors of stress-responsive transcription factors like NF-kappaB might be clinically useful for the suppression of the severity of acute pancreatitis.

The quality of the antioxidant defence system in term and preterm twin neonates.

OBJECTIVE: Multiple pregnancy is associated with an enhanced metabolism and demand for O2, which may lead to the overproduction of reactive oxygen species and the development of oxidative stress. The degree of oxidative damage depends on the level of the antioxidant protection system of the foetus. The objective of the study was to identify the relationship between the state of the maturity and the antioxidant status of twin neonates. Investigations of the umbilical cord blood were carried out to detect differences in the antioxidant defence system between mature and premature twin neonates. METHODS: The activities of the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes, the levels of reduced glutathione (GSH), protein carbonyls and oxidized lipids and the total antioxidant capacity of the plasma were determined. RESULTS: The level of lipid peroxidation was significantly higher in the premature neonates. An increase in the total antioxidant capacity was accompanied by a decrease in the damaged protein concentration. Significantly elevated activities of GPx alone were observed in the premature twins, though the GSH content too tended to be increased. The activity of SOD was decreased in the premature neonates. DISCUSSION: The antioxidant status of twin neonates are mainly influenced by maturity. We suggest that the level of lipid peroxidation might be of clinical value as a marker of pre- and perinatal distress in twins.

Nontoxic heat shock protein coinducer BRX-220 protects against acute pancreatitis in rats.

BACKGROUND: Nontoxic heat shock protein (HSP) inducer compounds open up promising therapeutic possibilities by activating one of the natural and highly conserved defense mechanisms of the organism. AIMS: In the present experiments, we examined the effects of a HSP coinducer drug-candidate, BRX-220, on the cholecystokinin-octapeptide (CCK)-induced acute pancreatitis in rats. METHODS: Male Wistar rats weighing 240 to 270 g were divided into two groups. In group B, 20 mg/kg BRX-220 was administered orally, followed by 75 microg/kg CCK subcutaneously three times, after 1, 3, and 5 h. This whole procedure was repeated for 5 d. The animals in group slashed circleB received physiological saline orally instead of BRX-220, but otherwise the protocol was the same as in group B. The rats were exsanguinated through the abdominal aorta 12 h after the last administration of CCK. We determined the serum amylase activity, the plasma trypsinogen activation peptide concentration, the pancreatic weight/body weight ratio, the DNA and total protein contents of the pancreas, the levels of pancreatic HSP60 and HSP72, the activities of pancreatic amylase, lipase, trypsinogen, and free radical scavenger enzymes (superoxide dismutase, catalase, and glutathione peroxidase), the degree of lipid peroxidation, protein oxidation, and the reduced glutathione level. Histopathological investigation of the pancreas was also performed in all cases. RESULTS: Repeated CCK treatment resulted in the typical laboratory and morphological changes of experimentally induced pancreatitis. The pancreatic levels of HSP60 and HSP72 were significantly increased in the animals treated with BRX-220. In group B, the pancreatic total protein content and the amylase and trypsinogen activities were significantly higher vs. group slashed circleB. The plasma trypsinogen activation peptide concentration, and the pancreatic lipid peroxidation, protein oxidation, and the activity of Cu/Zn-superoxide dismutase were significantly decreased in group B vs. group slashed circleB, whereas the glutathione peroxidase activity was increased. The morphological damage in group B was significantly lower than that in group slashed circleB. CONCLUSION: The HSP coinducer BRX-220, administered for 5 d, has a protective effect against CCK-induced acute pancreatitis.

The effects of hypo- and hyperthermic pretreatment on sodium taurocholate-induced acute pancreatitis in rats.

INTRODUCTION: Heat shock proteins (HSPs) have indispensable functions in the synthesis, degradation, folding, transport, and translocation of intracellular proteins. HSPs are proteins that help cells to survive stress conditions by repairing damaged proteins. AIM: To investigate the potential effects of HSP preinduction by cold-water (CWI) or hot-water immersion (HWI) on sodium taurocholate (TC)-induced acute pancreatitis in rats. METHODOLOGY: TC was injected into the common biliopancreatic duct of the animals at the peak level of HSP synthesis, as determined by Western blot analysis. The rats were killed by exsanguination through the abdominal aorta 6 hours after the TC injection. The serum amylase activity, the IL-1, IL-6 and TNF-alpha levels, the pancreatic weight/body weight ratio, and the pancreatic contents of DNA, protein, amylase, lipase, and trypsinogen were measured, and a biopsy for histology was taken. RESULTS: HWI significantly elevated HSP72 expression, whereas CWI significantly increased HSP60 expression. It was demonstrated that CWI pretreatment ameliorated the pancreatic edema and the serum amylase level increase, whereas the morphologic damage was more severe in this form of acute pancreatitis. HWI pretreatment did not have any effects on the measured parameters in TC-induced pancreatitis. CONCLUSIONS: The findings suggest a possible role of HSP60, but not HSP72, in the slight protection in the early phase of this necrohemorrhagic pancreatitis model.

Effects of octreotide on acute necrotizing pancreatitis in rabbits.

AIM: To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis, and to evaluate the preventive effects of octreotide towards the development of acute pancreatitis. METHODS: Acute pancreatitis was induced in male New Zealand white rabbits by retrograde injection of 0.8 mL/kg.b.m. of 50 g/L sodium taurocholate (NaTC) in the pancreatic duct. Sham-operated animals served as control. Octreotide 1 mg/kg.b.m. was administered subcutaneously before the induction of pancreatitis. Blood was taken from the jugular vein before and at 1, 3, 6, 12 and 24 h after pancreatitis induction. Serum activities of amylase, IL-6 and TNF-alpha and levels of malonyl dialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn-, Cu-, and Zn-SOD) in pancreatic tissue were measured. RESULTS: Serum TNF-alpha and IL-6 levels increased significantly 3 h after the onset of pancreatitis, and then returned to control level. The tissue concentration of MDA was significantly elevated at 24 h, while the GSH level and GP-x, catalase, Mn-SOD, Cu-, Zn-SOD activities were all significantly decreased in animals with pancreatitis as compared to the control. Octreotide pretreatment significantly reversed the changes in cytokines and reactive oxygen metabolites. Octreotide treatment did not alter the serum amylase activity and did not have any beneficial effects on the development of histopathological changes. CONCLUSION: Oxygen-derived free radicals and proinflammatory cytokines are generated at an early stage of NaTc-induced acute pancreatitis in rabbits. Prophylactic octreotide treatment can prevent release of cytokines and generation of reactive oxygen metabolites, but does not have any beneficial effects on the development of necrotizing pancreatitis.