Desferrioxamine Attenuates Pancreatic Injury after Major Hepatectomy under Vascular Control of the Liver: Experimental Study in Pigs (original) (raw)
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Pancreatic injury after major hepatectomy: a study in a porcine model
Purpose The aim of this study was to investigate the pathophysiology of pancreatitis after major hepatectomy. Methods The study used ten female pigs. Three served as sham animals (sham group) and were killed after laparot-omy to obtain normal tissue samples. Seven animals were subjected to major hepatectomy (70–75%), using the Pringle maneuver for 150 min, after constructing a porta-caval side-to-side anastomosis (hepatectomy group). Duration of reperfusion was 24 h. Results Pancreatic tissue sampled 24 h after reperfusion had increased necrosis and edema in comparison to sham group and to tissue sampled at 12 h. Tissue malondialde-hyde (MDA) did not differ significantly between samples at 12 and 24 h but was increased in the hepatectomy group in comparison to sham animals. Percentage increase in portal MDA content during reperfusion was greater at 12 h of reperfusion in comparison to the increase after 24 h. Portal pressure increased significantly after 12 h of reperfusion. Serum amylase and C-peptide increased during reperfusion in comparison to baseline levels. Conclusions The findings suggest that intraoperative portal congestion is not the only cause of the development of pancreatitis after major hepatectomy. The oxidative markers suggest that reactive oxygen species produced during vascular control may be responsible as well.
Introduction: Ischemia-reperfusion (I-R) injury has long been regarded a primary factor for the physiological dys-function that can occur following major liver resection performed under vascular control. The aim of our study was to assess the effect of treatment with desferoxamine (DFO), a potent antioxidative agent, monitoring the I-R injury on a porcine model of major hepatectomy. Materials and Methods: Twelve female pigs were allocated to control (n = 6) and DFO groups (n = 6) and underwent 30 min of liver ischemia, during which a ≥30% hepatec-tomy was performed, followed by six hours of postoperative monitoring. The DFO group animals were precondi-tioned with a continuous iv solution of DFO to a total dose of 100 mg/kg during their postoperative period. Liver remnants (≈70% of initial liver volume) were evaluated by means of infrared spectroscopy, serum lactate measurement of the systemic, portal and hepatic vein blood, and by immunohistochemical assessment of apoptosis in consecutive liver biopsies. Results: DFO group demonstrated considerably faster restoration of tissue oxygenation (92.33% vs. 80%, p < .05) and serum lactate values (1.23 mmol/l vs. 2.27 mmol/l, p < .05). Moreover, apoptosis as estimated by TUNEL and caspase-3 staining was significantly lower in the DFO group (0.06% vs. 1.17% and 1.17% vs. 2%, respectively, p < .05). The severity of the I-R injury showed a linear correlation to the restoration of tissue oxygenation, as estimated by infrared-spectroscopy (r 2 = 0.81, p < .01). Conclusion: Iron chelation with DFO appears to attenuate I-R injury of the liver remnant following hepatectomy, as reflected by faster restoration of tissue oxygenation and lower apoptotic activity.
Prostaglandins Leukotrienes and Essential Fatty Acids, 2006
Background: The aim of this study was to analyze the effects of 45 min of hepatic ischemia and 1 h of reperfusion on renal oxidative stress parameters, on renal tissue damage, and the role of Desferrioxamin (Dfx) and Q on these parameters. Methods: Thirty Wistar albino rats were randomized to five groups. Group I was the control group. Group II received no treatment. Groups III and IV received intramuscular injections of desferrioxamine (100 mg/kg) and quercetin (50 mg/kg), respectively. Group V was administered Dfx and quercetin in combination. After treatment for 3 days, groups II, III, IV, and V were exposed to total hepatic ischemia for 45 min. Plasma alanine aminotransferase levels, renal malondialdehyde and reduced glutathione (GSH) activities were measured after reperfusion for 1 h. Histopathological and ultrastructural analysis of renal tissues was carried out. Results: Plasma creatinine and BUN levels were markedly increased in the IR group and pretreated groups. Kidney MDA increased in the IR group, Q and Dfx+Q significantly decreased kidney MDA Kidney GSH levels markedly decreased in the IR group, Dfx significantly increased kidney GSH. No evidence of overt injury was observed in any renal tissue under light and electron microscopy. Conclusions: Our data demonstrated that 45 min of hepatic ischemia and 1 h of reperfusion may alter renal functions and may cause oxidative stress on renal tissue. Q and Dfx seem to have a beneficial effect via the GSH system and modulation of MDA levels. r
Critical Care, 2007
Hydrogen sulfide is produced endogenously by a variety of enzymes involved in cysteine metabolism. Clinical data indicate that endogenous levels of hydrogen sulfide are diminished in various forms of cardiovascular diseases. The aim of the current study was to investigate the effects of hydrogen sulfide supplementation on cardiac function during reperfusion in a clinically relevant experimental model of cardiopulmonary bypass. Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 minutes of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or the sodium sulfide infusion (1 mg/kg/hour, n = 6). Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and pulmonary blood flow, vasodilator responses to acetylcholine and sodiumnitroprusside and pulmonary function were also determined. Administration of sodium sulfide led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 minutes of reperfusion. Coronary blood flow was also significantly higher in the sodium sulfide-treated group (P < 0.05). Sodium sulfide treatment improved coronary blood flow, and preserved the acetylcholine-induced increases in coronary and pulmonary blood (P < 0.05). Myocardial ATP levels were markedly improved in the sulfide-treated group. Thus, supplementation of sulfide improves the recovery of myocardial and endothelial function and energetic status after hypothermic cardiac arrest during cardiopulmonary bypass. These beneficial effects occurred without any detectable adverse hemodynamic or cardiovascular effects of sulfide at the dose used in the current study.
Antioxidant preconditioning attenuates liver ischemia/reperfusion injury after hepatectomy in swine
Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 2021
PURPOSE The purpose of this study was to evaluate whether antioxidant preconditioning with Deferoxamine can attenuate liver ischemia reperfusion injury associated with extended hepatectomy in swine. METHODS Eighteen swine were randomly assigned to two groups: Deferoxamine (DFO) and Surgery Only (SO). The animals in both groups were subjected to laparotomy, prolonged temporary occlusion of the right and middle hepatic pedicles and subsequent left hepatectomy. The DFO group received IV deferoxamine prior to induction of liver ischemia. Monitoring was performed for 6 h and samples (Protein carbonyls, Thiobarbituric acid reactive substances, Histology, ALT, AST, Lactic acid and WBC) were drawn at 0, 60 and 360 min. RESULTS Protein carbonyls and Thiobarbituric acid reactive substances had significantly lower concentration and higher reduction rates in serum and liver tissue of the DFO group. The histological examination of liver tissue showed less inflammation and necrosis in the DFO gro...
Drug design, development and therapy, 2024
Pancreatic surgeries inherently cause ischemia-reperfusion (IR) injury, affecting not only the pancreas but also distant organs. This study was conducted to explore the potential use of dexmedetomidine, a sedative with antiapoptotic, anti-inflammatory, and antioxidant properties, in mitigating the impacts of pancreatic IR on kidney and liver tissues. Methods: A total of 24 rats were randomly divided into four groups: control (C), dexmedetomidine (D), ischemia reperfusion (IR), and dexmedetomidine ischemia reperfusion (D-IR). Pancreatic ischemia was induced in the IR and D-IR groups. Dexmedetomidine was administered intraperitoneally to the D and D-IR groups. Liver and kidney tissue samples were subjected to microscopic examinations after hematoxylin and eosin staining. The levels of thiobarbituric acid reactive substances (TBARS), aryllesterase (AES), catalase (CAT), and glutathione S-transferase (GST) enzyme activity were assessed in liver and kidney tissues. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine were measured. Results: A comparison of the groups revealed that the IR group exhibited significantly elevated TBARS (p < 0.0001), AES (p = 0.004), and CAT enzyme activity (p < 0.0001) levels in the liver and kidney compared to groups C and D. Group D-IR demonstrated notably reduced histopathological damage (p < 0.05) and low TBARS (p < 0.0001), AES (p = 0.004), and CAT enzyme activity (p < 0.0001) in the liver and kidney as well as low AST and ALT activity levels (p < 0.0001) in the serum compared to the IR group. Conclusion: The preemptive administration of dexmedetomidine before pancreatic IR provides significant protection to kidney and liver tissues, as evidenced by the histopathological and biochemical parameters in this study. The findings underscored the potential therapeutic role of dexmedetomidine in mitigating the multiorgan damage associated with pancreatic surgeries.
Ukraïnsʹkij žurnal nefrologìï ta dìalìzu, 2021
Recent studies have shown that renal ischemia-reperfusion injury can have detrimental effects on distant organs such as the brain, liver and lungs. In this study, we aimed to investigate the effects of renal ischemia-reperfusion injury on pancreatic functions. Materials and Methods. Twenty four male adult Wistar rats were divided into four groups. Sham and control group animals were not given any medications. Animals in groups 3 and 4 were treated with epidural bupivacaine and isoflurane inhalation. Animals in all groups except for the sham group were subjected to bilateral renal ischemia for 45 minutes and subsequent reperfusion. Blood samples were collected before ischemia, immediately after reperfusion and 2h after reperfusion. Serum blood urea nitrogen, creatinine, amylase and lipase levels were measured, and pancreatic sections were histopathologically examined for the presence and severity of congestion, degenerative cellular changes, cytoplasmic vacuolization and leukocytic infiltration. Levels of malondialdehyde, endogenous antioxidant enzyme catalase and reduced glutathione were measured in pancreatic tissue sections by using colorimetric kits. Results. Serum blood urea nitrogen and creatinine levels increased in rats subjected to renal ischemia-reperfusion. There was no difference between the groups in terms of pancreatic tissue malondialdehyde, catalase and glutathione levels. Conclusion. In conclusion, bilateral renal ischemia for 45 minutes led to significant impairment in pancreatic function and changes in pancreas histology. These findings might be due to antioxidant deficiency and increased lipid peroxidation in pancreatic tissue.
Resuscitation, 1989
Desferrioxamine mesylate (desferall an iron chelating agent was investigated in anaesthetized standard haemorrhagic shock (HS) dogs with elective hypotension at 35 f 5 mmHg for 4 h and return of withdrawn blood (ROWB) thereafter. Observations were made in respect of serum iron elevation over 4 h and survival and recovery pattern over 72 h after ROWB. Influence of the drug on histopathological changes of shock in liver were studied in non-survival experiments (dogs sacrificed after 4 h of elective hypotensionl. Desferal administration (25 mg/kg i.m.1 at 30 min after initial bleeding, increased the '72 h survival from 10% (controls) to 50%. and reduced the serum iron elevation from 63.3% (controls) to 9.44%. The single control survivor remained unconscious till 24 h and sluggish in activity up to 72 h. Three of the drug treated survivors regained consciousness by 2 h, activity by 24 h and all were normally active by 72 h. Severe congestive and degenerative changes in liver, present in the controls, were markedly reduced in severity and incidence in those given desferal. It is suggested that iron decompartmentalization in the hypoxic tissues in HS with its consequent rise in serum and intracellular pool, plays a pivotal role in progression towards irreversibility. Desferal, an effective intracellular iron chelator, possibly arrests the widespread cellular damage caused through enhanced iron-catalysed 'OH radical generation in shock state.