Analysis of two reperfusion techniques in uterine transplantation in an experimental model.

INTRODUCTION: Uterine transplantation was developed for the treatment of absolute uterine factor infertility. As it is a new modality of transplantation, there is still room for technical improvement. A factor that impacts graft survival in organ transplantation is the warm ischemia time. In uterine transplantation specifically, at least two vascular anastomoses are performed on each side of the uterus, and the graft revascularization takes place when the vascular clamps of the arteries and veins are released on both sides simultaneously. For this reason, the warm ischemia time in uterine transplant is expected to be considerably long. The purpose of this study was to compare the sequential technique of uterine graft revascularization, which aims to reduce the warm ischemia time of the procedure, with the simultaneous revascularization technique. MATERIAL AND METHODS: For the procedure, the uterine auto-transplantation technique was performed using 10 non-pregnant adult ewes weighing about 45 kg, divided into two groups: simultaneous revascularization group (5 animals) and sequential revascularization group (5 animals). To evaluate the groups, we analyzed the procedure and warm ischemia times, graft macroscopy, hemodynamic, laboratory, and histological parameters of the uterus. RESULTS: The sequential revascularization technique group had similar surgical procedure times, and the warm ischemia time was significantly shorter with medians of 32 min in the sequential group versus 72 min in the simultaneous group (p < 0.008). The graft macroscopy and hemodynamic, laboratory, and histological parameters evaluated were similar between the groups. CONCLUSIONS: The sequential revascularization technique proved to reduce the warm ischemia time in the sheep uterine auto-transplantation model without compromising graft viability.

The Effect of Ascorbic Acid on Hepatic Ischaemia-Reperfusion Injury in Wistar Rats: An Experimental Study.

Liver ischaemia-reperfusion (IR) during hepatic surgeries can lead to liver cell death via oxidative stress and the activation of immune cells, the release of cytokines, and damage-associated molecular patterns. Ascorbic acid has been shown to confer potential protective effects against IR injury, mainly due to its antioxidant properties. This study evaluated the effect of ascorbic acid infusion at different time points during hepatic IR in rats. Thirty-six male Wistar rats were divided into control and experimental groups that received the same total ascorbic acid dose at three different infusion times: before ischaemia, before reperfusion, or before both ischaemia and reperfusion. All of the animals experienced hepatic IR injury. We measured the hepatic enzymes, cytokines, and portal blood flow. Animals receiving ascorbic acid before both ischaemia and reperfusion had lower liver enzyme levels, reduced inflammation, and better portal venous flow than other animals. Divided doses of ascorbic acid before IR may be beneficial for reducing liver injury associated with IR.

Nuclear factor kappa-light-chain-enhancer of activated B cells gene expression involvement in porcine liver transplant experimental model.

PURPOSE: Gene expressions of vascular Endothelial Growth Factor Alpha (VEGFa), Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B cells (NFkB) and cytokines could be useful for identifying potential therapeutic targets to alleviate ischemia-reperfusion injury after liver transplantation. Cytokine gene expressions, VEGFa and NFkB were investigated in a preclinical swine model of liver transplantation. METHODS: A total of 12 pigs were used as donors and recipients in liver transplantation without venovenous bypass or aortic clamping. NFkB, IL-6, IL-10, VEGFa and Notch1 gene expression were assessed. These samples were collected in two specific times: group 1 (n= 6) - control, samples were collected before recipient's total hepatectomy and group 2 - liver transplantation group (n=6), where the samples were collected one hour after graft reperfusion. RESULTS: Liver transplantation was successfully performed in all recipients. Liver enzymes were elevated in the transplantation group. NFkB gene expression was significantly decreased in the transplantation group in comparison with the control group (0.62±0.19 versus 0.39±0.08; p= 0.016). No difference was observed between groups Interleucine 6 (IL-6), interleucine 10 (IL-10), VEGFa and Notch homolog 1 (Notch1). CONCLUSIONS: In this survey a decreased NFkB gene expression in a porcine model of liver transplantation was observed.

En Bloc Simultaneous Liver-Kidney Transplantation Compared to the Traditional Technique: Results From a Single Center.

BACKGROUND: Simultaneous liver-kidney transplantation is indicated for patients with concomitant end-stage liver disease and end-stage renal disease. The traditional technique involves separate implantations of the liver and the kidney. In the en bloc approach, the liver is recovered en bloc with the right kidney and the donor renal artery is anastomosed to the donor splenic artery. We aimed to compare the outcomes of the traditional and en bloc techniques for simultaneous liver-kidney transplantation in a single center. METHODS: This single-center retrospective study involved all adult patients who underwent simultaneous liver-kidney transplantation from brain-dead donors from January 2017 to December 2022. RESULTS: A total of 15 patients were included: 10 transplanted with the traditional technique and 5 with the en bloc approach. Patients in the en bloc group presented higher body mass index, shorter kidney cold and total ischemia times, shorter overall surgical time and longer kidney warm ischemia time (29.07 kg/m2vs 23.20 kg/m2 [P = .048]; 560 minutes vs 880 minutes [P = .026]; 615 minutes vs 908 minutes [P = 0.025]; 405 minutes vs 485 minutes [P = .046]; 46 minutes vs 33.5 minutes [P = 0.027], respectively). Ureteroneocystostomy was performed in 2 patients of the en bloc group and ureteroureterostomy in the remaining 3 patients. One patient in the en bloc group presented stenosis of renal artery anastomosis and underwent percutaneous angioplasty. This same patient eventually developed late urinary fistula. In the traditional technique group, there were 2 cases of renal vein thrombosis and 1 of ureteral stenosis. CONCLUSIONS: Compared with the traditional technique, the en bloc approach is feasible and safe, reducing kidney total ischemia time and overall surgical time.

Liver Transplantation for Benign Massive Hepatomegaly: Results From a Single Center and Contribution of the Left-to-Right Piggyback Approach.

INTRODUCTION: Polycystic liver disease and giant hepatic hemangioma may present with severe symptom burden and indicate orthotopic liver transplantation. The left-to-right piggyback approach is a useful technique for performing total hepatectomy of enlarged livers. OBJECTIVE: The purpose of this study is to analyze the results of liver transplantation in patients with benign massive hepatomegaly. METHODS: This is a single-center retrospective study involving all adult patients who underwent liver transplantation due to benign massive hepatomegaly from January 2002 to June 2023. RESULTS: A total of 22 patients underwent liver transplantation (21 cases of polycystic live disease and 1 case of giant hepatic hemangioma). During the same time, there were 2075 transplants; therefore, benign massive hepatomegaly accounted for 1.06% of cases. Most patients (59.09%) were transplanted using the left-to-right piggyback technique. Seven patients had previous attempted treatment of hepatic cysts. Another patient previously underwent bilateral nephrectomy and living-donor kidney transplantation. Among these patients, in 5 cases there were massive abdominal adhesions with increased bleeding. Four of these 8 patients died in the very early perioperative period. In comparison to patients without previous cysts manipulation, massive adhesions and perioperative death were significantly higher in those cases (62.5 vs 0%, P = .002 and 50% vs 0%, P = .004, respectively). CONCLUSION: Liver transplantation due to polycystic liver disease and giant hemangioma is a rare event. Total hepatectomy is challenging due to the enlarged native liver. The left-to-right piggyback technique is useful, because it avoids vena cava twisting and avulsion of its branches. Massive adhesions due to previous cysts manipulation may lead to increased bleeding, being a risk factor for mortality.

Retransplantation for Late Hepatic Artery Thrombosis: Results from a Single Center.

BACKGROUND: Hepatic artery thrombosis is the most common vascular complication of liver transplantation. When occurring late in the postoperative course, it may have no clinical repercussions, and conservative treatment may be implemented. Some patients, however, will develop severe biliary complications due to ischemic cholangiopathy and require retransplantation. The aim of this study is to report the outcomes of retransplantation in this population. METHODS: This is a single-center retrospective study involving all adult patients who underwent liver retransplantation due to late hepatic artery thrombosis from January/2010 to December/2022. RESULTS: During the study period, 1378 liver transplants were performed in our center; 147 were retransplantations, with 13 cases of late hepatic artery thrombosis (0.94%). All had symptomatic ischemic cholangiopathy. Twelve of them had already presented previous cholangitis, bilomas, or liver abscesses and had undergone biliary stenting or percutaneous drainage. The median time between the first liver transplant and late hepatic artery thrombosis diagnosis and between this diagnosis and retransplantation were 73 and 50 days, respectively. Arterial reconstruction using splenic artery, celiac trunk, or arterial conduit from the aorta was performed in 7 cases, whereas biliary reconstruction was mostly done with choledochojejunostomy (n = 8). There were 4 perioperative deaths, 2 due to primary non-function and 2 due to refractory shock after exceedingly complex retransplants. CONCLUSION: Liver retransplantation due to late hepatic artery thrombosis is a rare condition that should be offered to patients who develop severe biliary complications and recurrent infections. It is nonetheless a challenging procedure associated with significant perioperative mortality.

Liver Transplantation for Adenomatosis: A Single-Center Experience.

BACKGROUND: Liver adenomatosis is characterized by multiple adenomas diffusely distributed throughout the liver parenchyma. Studies addressing liver transplantation for those cases are scarce, and the criteria used to indicate transplantation are still debatable. OBJECTIVE: To report a single-center experience of liver transplantation for diffuse adenomatosis. METHODS: Single-center retrospective study involving all adult patients who underwent liver transplantation due to adenomatosis from January/2010 to June/2023. RESULTS: A total of 13 patients were identified, corresponding to 0.89% of liver transplants performed during the study period. The mean age was 33 ± 6.55 years, and most of them were female (n = 9, 69.23%). There were 12 transplants with deceased donors and 1 with a right lobe from a living donor. The most frequent reason to preclude liver resection was multiple and large unresectable adenomas in patients without previous liver disease (n = 8, 61.58%), followed by underlying liver disease (Abernethy Malformation, n = 3, 23.07%) and recurrence after liver resection (n = 2, 15.38%). The indications for liver transplantation were high risk of malignant transformation (n = 7, 53.84%), increasing size and number of nodules (n = 3, 23.07%), confirmed malignant transformation (n = 2, 15.38%), and hemorrhage (n = 2, 15.38%). There was 1 perioperative death due to primary non-function. Another patient died during follow-up because of COVID-19. CONCLUSION: Liver adenomatosis is a rare indication for liver transplantation, with acceptable post-transplant outcomes. Unresectable adenomas with high-risk or confirmed malignant transformation are the main indications for transplant. Reasons for unresectability involve underlying liver disease, multiple and large high-risk nodules, and recurrence after previous resection.

Anatomic and Surgical Aspects of Total Pancreatectomy in Swine.

BACKGROUND: The swine is a valuable model for preclinical research and surgical technique training. Induction of Type I diabetes is achieved by total pancreatectomy, therefore these animals may be used in several research studies, including islet transplantation field. Given the lack of information in the literature, the purpose of this work is to describe anatomic aspects of swine pancreas, the total pancreatectomy surgical technique, intra- and postoperative complications and the autopsy results. MATERIAL AND METHODS: Five hybrid male pigs, 20-35 kg, submitted to total pancreatectomy with duodenum, bile duct, and spleen preservation. Postoperatively, daily clinical assessment and capillary blood glucose collection were performed. At the end of the 30-day period or in the occurrence of serious clinical complications, euthanasia and autopsy were performed. RESULTS: The average duration of surgery was 128 minutes, without intraoperative deaths or anesthesia induction failures. The median survival was 6.6 days. Postoperative complications were weight loss (3), emesis (2), constipation (2), abdominal distension (2), diarrhea (1), and loss of appetite (1). All animals were euthanized due to serious complications. Two animals presented surgical complications (duodenal necrosis with gastroparesis and internal hernia with intestinal necrosis). The other 3 animals presented serious clinical complications related to exocrine pancreatic insufficiency due to deficiency of pancreatic enzymes. Glycemic values above 200 mg/dL were found on the first postoperative day and above 300 mg/dL on the seventh day in all animals. CONCLUSION: A model of total pancreatectomy with duodenum, spleen, and bile duct preservation in pigs was established. All animals became diabetic, however, animals without postoperative complications were euthanized due to serious complications related to pancreas exocrine insufficiency.

Nuclear factor kappa-light-chain-enhancer of activated B cells gene expression involvement in porcine liver transplant experimental model

Purpose: Gene expressions of vascular Endothelial Growth Factor Alpha (VEGFa), Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B cells (NFkB) and cytokines could be useful for identifying potential therapeutic targets to alleviate ischemia-reperfusion injury after liver transplantation. Cytokine gene expressions, VEGFa and NFkB were investigated in a preclinical swine model of liver transplantation. Methods: A total of 12 pigs were used as donors and recipients in liver transplantation without venovenous bypass or aortic clamping. NFkB, IL-6, IL-10, VEGFa and Notch1 gene expression were assessed. These samples were collected in two specific times: group 1 (n= 6) - control, samples were collected before recipient's total hepatectomy and group 2 - liver transplantation group (n=6), where the samples were collected one hour after graft reperfusion. Results: Liver transplantation was successfully performed in all recipients. Liver enzymes were elevated in the transplantation group. NFkB gene expression was significantly decreased in the transplantation group in comparison with the control group (0.62±0.19 versus 0.39±0.08; p= 0.016). No difference was observed between groups Interleucine 6 (IL-6), interleucine 10 (IL-10), VEGFa and Notch homolog 1 (Notch1). Conclusions: In this survey a decreased NFkB gene expression in a porcine model of liver transplantation was observed.

Study of laser fluorescence spectroscopy in livers of rats with hypothermic ischemia.

PURPOSE: After partial hepatectomy (PH), the remaining liver (RL) undergoes regenerative response proportional to the host. Limited literature exists on hepatic viability after tissue injury during hypothermic preservation. Spectroscopy measures cellular fluorescence and is explored for tissue characterization and parameter investigation. This study aimed to assess fluorescence analysis (spectroscopy) in evaluating liver viability and its relationship with hepatic tissue regeneration 24 hours after PH. Additionally, we analyzed liver regeneration in RL after 70% partial hepatectomy under hypothermic conditions with laser irradiation. METHODS: Fifty-six Wistar rats were divided into four groups: total non-perfused liver (control), total perfused liver, partial hepatectomy "in situ", and partial hepatectomy "ex situ". Tissue analysis was performed at 0 and 24 hours using spectroscopy with laser devices emitting at 532 (green) and 405 nm (violet). RESULTS: Spectroscopy identified tissue viability based on consistent results with Ki67 staining. The fluorescence spectra and Ki67 analysis displayed similar patterns, linking proliferative activity and absorption intensity. CONCLUSIONS: Fluorescence spectroscopy proves to be promising for real-time analysis of cellular activity and viability. Metabolic activity was observed in groups of live animals and hypothermically preserved samples, indicating cellular function even under blood deprivation and hypothermic conditions.

PRECLINICAL MODELS OF LIVER CÂNCER.

•In this review, we described different murine models of carcinogenesis: classic models, new transgenic and combined models, that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic physiopathological, and environmental abnormalities. •Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches. •Cholangiocarcinoma has been highlighted, with an increase in prevalence. This review has an important role in understanding the pathophysiology and the development of new drugs. Background - This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective - A review through MEDLINE and EMBASE was performed to assess articles until August 2022.Methods - Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results - In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion - Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.

Modelos pré-clínicos de câncer hepático / Preclinical models of liver câncer

ABSTRACT Background: This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective: A review through MEDLINE and EMBASE was performed to assess articles until August 2022. Methods: Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results: In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion: Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.

RESUMO Contexto: Este manuscrito fornece uma visão geral da carcinogênese hepática em modelos murinos de carcinoma hepatocelular (CHC) e colangiocarcinoma (CCA). Objetivo: Realizar uma revisão de artigos científicos até agosto de 2022 utilizando as bases de dados MEDLINE e EMBASE. Métodos: A busca foi realizada em todas as bases de dados eletrônicas e as palavras-chave usadas foram CHC, CCA, carcinogenesis, modelos animais e fígado. A exclusão dos artigos baseou-se na falta de estreita relação com o assunto. Os modelos de carcinogênese do CHC incluíram: CHC induzido por senescência em animais transgênicos, CHC induzido por dieta, CHC induzido por agentes quimiotóxicos, xenoenxerto, oncogenes e CHC em animais transgênicos inoculados com vírus B e C. Os modelos de CCA incluíram: o uso de dimetilnitrosamina (DMN), dietilnitrosamina (DEN), tioacetamida (TAA) e tetracloreto de carbono (CCl4). Os modelos murinos de CCA induzidos por incluir: células de CCA, manipulação genética, animais nocaute para Smad4, PTEN e p53, xenoenxerto e ligadura do ducto biliar mediano esquerdo. Resultados: Nesta revisão, descrevemos diferentes modelos murinos de carcinogênese que reproduzem os pontos-chave para a gênese do CHC e do CCA, permitindo uma melhor compreensão de suas anormalidades genéticas, fisiopatológicas e ambientais. Conclusão: Cada modelo tem suas vantagens, desvantagens, semelhanças e diferenças com a doença humana correspondente e deve ser escolhido de acordo com a especificidade do estudo. Em última análise, esses modelos também podem ser utilizados para testar novas abordagens terapêuticas anticancerígenas.

The Protective Effect of Nutraceuticals on Hepatic Ischemia-Reperfusion Injury in Wistar Rats.

Nutraceuticals are bioactive compounds present in foods, utilized to ameliorate health, prevent diseases, and support the proper functioning of the human body. They have gained attention due to their ability to hit multiple targets and act as antioxidants, anti-inflammatory agents, and modulators of immune response and cell death. Therefore, nutraceuticals are being studied to prevent and treat liver ischemia-reperfusion injury (IRI). This study evaluated the effect of a nutraceutical solution formed by resveratrol, quercetin, omega-3 fatty acid, selenium, ginger, avocado, leucine, and niacin on liver IRI. IRI was performed with 60 min of ischemia and 4 h of reperfusion in male Wistar rats. Afterward, the animals were euthanized to study hepatocellular injury, cytokines, oxidative stress, gene expression of apoptosis-related genes, TNF-α and caspase-3 proteins, and histology. Our results show that the nutraceutical solution was able to decrease apoptosis and histologic injury. The suggested mechanisms of action are a reduction in gene expression and the caspase-3 protein and a reduction in the TNF-α protein in liver tissue. The nutraceutical solution was unable to decrease transaminases and cytokines. These findings suggest that the nutraceuticals used favored the protection of hepatocytes, and their combination represents a promising therapeutic proposal against liver IRI.

Multivisceral transplantation of pelvic organs in rats.

Background: Multivisceral transplantation of pelvic organs would be a potential treatment for severe pelvic floor dysfunction with fecal and urinary incontinence, extensive perineal trauma, or congenital disorders. Here, we describe the microsurgical technique of multivisceral transplantation of pelvic organs, including the pelvic floor, in rats. Donor operation: We performed a perineal (including the genitalia, anus, muscles, and ligaments) and abdominal incision. The dissection progressed near the pelvic ring, dividing ligaments, muscles, external iliac vessels, and pudendal nerves, allowing pelvic floor mobilization. The aorta and vena cava were isolated distally, preserving the internal iliac and gonadal vessels. The graft containing the skin, muscles, ligaments, bladder, ureter, rectum, anus and vagina, uterus and ovarian (female), or penile, testis and its ducts (male) was removed en bloc, flushed, and cold-stored. Recipient operation: The infrarenal aorta and vena cava were isolated and donor/recipient aorta-aorta and cava-cava end-to-side microanastomoses were performed. After pelvic floor and viscera removal, we performed microanastomoses between the donor and the recipient ureter, and the rectum and pudenda nerves. The pelvic floor was repositioned in its original position (orthotopic model) or the abdominal wall (heterotopic model). We sacrificed the animals 2 h after surgery. Results: We performed seven orthotopic and four heterotopic transplantations. One animal from the orthotopic model and one from the heterotopic model died because of technical failure. Six orthotopic and three heterotopic recipients survived up to 2 h after transplantation. Conclusion: The microsurgical technique for pelvic floor transplantation in rats is feasible, achieving an early survival rate of 81.82%.

Study of laser fluorescence spectroscopy in livers of rats with hypothermic ischemia

Purpose: After partial hepatectomy (PH), the remaining liver (RL) undergoes regenerative response proportional to the host. Limited literature exists on hepatic viability after tissue injury during hypothermic preservation. Spectroscopy measures cellular fluorescence and is explored for tissue characterization and parameter investigation. This study aimed to assess fluorescence analysis (spectroscopy) in evaluating liver viability and its relationship with hepatic tissue regeneration 24 hours after PH. Additionally, we analyzed liver regeneration in RL after 70% partial hepatectomy under hypothermic conditions with laser irradiation. Methods: Fifty-six Wistar rats were divided into four groups: total non-perfused liver (control), total perfused liver, partial hepatectomy "in situ", and partial hepatectomy "ex situ". Tissue analysis was performed at 0 and 24 hours using spectroscopy with laser devices emitting at 532 (green) and 405 nm (violet). Results: Spectroscopy identified tissue viability based on consistent results with Ki67 staining. The fluorescence spectra and Ki67 analysis displayed similar patterns, linking proliferative activity and absorption intensity. Conclusions: Fluorescence spectroscopy proves to be promising for real-time analysis of cellular activity and viability. Metabolic activity was observed in groups of live animals and hypothermically preserved samples, indicating cellular function even under blood deprivation and hypothermic conditions.

Hexafluoroisopropanol decreases liver ischemia-reperfusion injury by downregulation of high mobility group box-1 protein.

Liver ischemia-reperfusion (IR) injury is associated with poor outcome after liver transplantation and liver resections. Hexafluoroisopropanol (HFIP) is a tri-fluorinated metabolites of volatile anesthetics and has modulatory effects on inflammation that have been observed mainly in cell culture experiments. In this survey, we investigated the effects of HFIP in a rat model of normothermic hepatic ischemia-reperfusion injury. Twenty-four male Wistar rats were randomized into three groups: (1) control in which animals were submitted to 30 min of partial liver ischemia with resection of non-ischemic liver lobes immediate after reperfusion, (2) pre-ischemia (PI) group in which animals received intravenous HFIP (67 mg/kg) 5 min before liver ischemia, and (3) pre-reperfusion (PR) group in which animals received intravenous HFIP (67 mg/kg) 5 min before reperfusion. Four hours after reperfusion, all animals were euthanized for sample collection. Aspartate and alanine transaminases, glucose, and high mobility group box-1 (HMGB-1) protein concentrations showed a significant decreased, and malondialdehyde was increased in the PR group compared with control and PI groups. Interleukin 6 (IL-6) was increased in the PI group compared with control and PR groups. IL-10 and -12 were increased in the PR and PI groups, respectively, when compared with the control group. Glucose decreased in the PR when compared with the control group. Post-conditioning with HFIP led to a decrease in hepatocellular injury and was associated with a downregulation of HMGB-1. The HFIP resulted in a better control of inflammatory response to ischemia-reperfusion even without causing a reduction in oxidative stress.