reperfusion

Liver transplantation (LT) is a critical intervention for pediatric patients with advanced liver failure. This study aimed to assess the impact of perioperative factors on LT outcomes in pediatric patients. This retrospective cohort study, conducted from 2010-2020, included 563 pediatric patients who underwent LT in Shiraz, Iran. Most patients received liver grafts from living donors due to cholestatic and metabolic diseases, and all had complete medical and laboratory records. Data were analyzed using various regression models (Cox, linear, and logistic) in SPSS software (version 22). Of the 563 patients who underwent LT, 436 received livers from living donors and 127 from deceased donors. The primary diagnoses included cholestatic diseases (44.4%) and metabolic diseases (34.1%). Post-transplant rejection and mortality rates were 21.1% (119 patients) and 36.1% (203 patients), respectively. Preoperative factors associated with rejection included weight (HR=1.01, P=0.01) and albumin (HR=0.69, P=0.03). Postoperative factors influencing rejection included platelet transfusion (HR=2.12, P=0.03), primary non-function (PNF) (HR=4.6, P=0.01), cytomegalovirus (CMV)(HR=1.78, P=0.005), and convulsion (HR=1.93, P=0.007). Preoperative factors that affect mortality were age (HR=0.89, P<0.001), alanine aminotransferase (ALT) (HR=1, P=0.047), and hemoglobin levels (HR=0.91, P=0.03). Intraoperative factors influencing mortality included cold ischemia duration (HR=0.98, P=0.048) and anhepatic blood loss (HR=1.02, P<0.001). Postoperative factors associated with mortality included fresh frozen plasma (FFP) transfusion (HR=1.7, P=0.004), bleeding (HR=2.17, P=0.009), bowel perforation (HR=2.55, P=0.01), and PNF (HR=11.24, P<0.001).  Optimizing perioperative care practices could significantly improve LT outcomes in pediatric patients.

Post-reperfusion syndrome (PRS) during liver allograft reperfusion is characterized by hemodynamic instability, including hypotension, bradycardia, and arrhythmias. The incidence and risk factors of PRS are primarily studied in cadaveric liver transplantation. This study aims to estimate the incidence of PRS and identify associated factors in living donor liver transplantation (LDLT).

To estimate the incidence of PRS and evaluate factors associated with its development in LDLT.

We prospectively observed 70 adult patients with chronic liver disease who underwent LDLT between August 2020 and March 2022. Patients were categorized into two groups: those who developed PRS (PRS group) and those who did not (non-PRS group).

PRS occurred in 26 of 70 recipients (37.1%). The PRS group had significantly higher mean MELD scores, lower preoperative fibrinogen levels, and longer graft cold ischemia times (p= 0.027, p= 0.015, p= 0.045, respectively). These patients also experienced greater intraoperative blood loss and required more blood product transfusions. Postoperatively, the PRS group had longer mechanical ventilation times, a prolonged vasopressor requirement, and higher peak bilirubin levels in the first 7 days (p= 0.009, p= 0.001, p= 0.002, respectively).

PRS is associated with more severe liver disease, greater intraoperative blood loss, and higher blood product transfusions. Postoperatively, patients with PRS had longer mechanical ventilation, prolonged vasopressor use, and elevated bilirubin levels.

Anemoside B4 (AB4) is a multifunctional compound with anti-inflammatory, anti-apoptotic, antioxidant, antiviral, and autophagy-enhancing effects. However, the role of AB4 in cerebral ischemia/reperfusion injury (CIRI) remains obscure. This experiment aims to investigate the pharmacological effects of AB4 in CIRI.

In vivo, eighty male SD rats were randomly divided into five groups: sham, MCAO/R, LD group (2.5 mg/kg), MD group (5 mg/kg), and HD group (10 mg/kg). The rats in sham and MCAO/R groups were given equal volumes of normal saline. In vitro, PC12 cells were divided into five groups: normal, OGD/R, OGD/R+AB4 (50 μM), OGD/R+AB4 (100 μM), and OGD/R+AB4 (200 μM). The cells were treated with hypoxia and hypoglycemia for 1.5 hr and reoxygenation for 24 hr.

In vivo, TTC and neurological scoring tests indicated that AB4 favors promoting the recovery of the brain. The histopathologic study of the brain tissues revealed that AB4 inhibited the damage of neuron cells. The TUNEL assay found that AB4 could improve cell apoptosis and prevent the brain from injury. In vitro, the data showed that AB4 inhibited cell damage and prevented PC12 cells from OGD/R injury, reduced IL-1β content, and increased the IL-10 level. AB4 could inhibit apoptosis of PC12 cells, down-regulate Caspase 12 and BAX expression, and up-regulate Bcl-2 expression.

AB4 played a protective role in CIRI and could be a promising active ingredient against ischemia stroke.

Liver ischemia-reperfusion (I/R) is the director’s origin of damages in various clinical situations, especially surgery and transplantation. Inflammatory damages are critical because of the chronicity of I/R injuries (I/RI). The hepatoprotective and antiinflammatory properties of silibinin have been reported in different studies. This study aimed to investigate the effect of Silibinin on the expression of the pannexin-1 (Panx1) gene during hepatic I/R.

In this case-control animal study, a total of 32 male Wistar rats (n=8 in each) were surveyed. The animals were randomly assigned into four equal groups as follows: Group 1 (Control): the rats underwent a midline laparotomy with normal saline injection; Group 2 (SILI): the rats received Silibinin (50 mg/kg) after laparotomy; Group 3 (I/R): the rats underwent I/R surgery and received normal saline; and Group 4 (I/R+SILI): the rats received silibinin before ischemia and directly following reperfusion. Blood and liver tissue samples were taken after three hours of reperfusion aftermath 1-hour ischemia to evaluate histological changes, gene expression, and serum markers of hepatic injury.

While the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the I/R group significantly increased compared to the control group (P<0.001), they significantly decreased in the SILI+I/R group (P<0.001). Silibinin ameliorated inflammatory impairments of liver tissue, such as neutrophil and macrophage infiltration and activation, hepatocyte degeneration and vacuolation, hepatic vascular endothelial damage, and sinusoid proliferation in the I/R group. The expression of the Panx1 mRNA during I/R significantly increased compared to the control group (P<0.001), but silibinin reduced the expression (P<0.001).

We witnessed that silibinin reduced liver tissue damages during hepatic I/R. Correcting the expression of the Panx1 gene during I/R is probably one of the mechanisms of anti-inflammatory effects of silibinin.

Myocardial arrhythmia is a major complication of ischemia-reperfusion (I/R) injury in patients with diabetes. Irisin has significant cardioprotective effects, while its role in the pathophysiology of I/R injury-induced myocardial arrhythmia in the presence of diabetes is not well identified. Here, we aimed to investigate the potential antiarrhythmic impacts and mechanisms (mitochondrial biogenesis, endoplasmic reticulum (ER) stress, and pyroptosis) by which irisin reduces I/R injury-induced myocardial arrhythmia in diabetic rats.

Thirty high-fat diet-induced diabetic rats were subjected to I/R injury and myocardial arrhythmia. Irisin (0.5 μg/kg/day) was injected intraperitoneally before induction of I/R injury. Electrocardiography was used to measure the incidence and severity of ventricular arrhythmias. ELISA and western blotting analyses were employed to quantify the expression of mitochondrial biogenesis, ER stress, and pyroptosis-related proteins in ischemic myocardium.

Irisin treatment in diabetic rats significantly decreased the lactate dehydrogenase level and the number and severity of arrhythmia induced by I/R injury. Irisin up-regulated the expression of mitochondrial biogenesis-related proteins while down-regulating the expression of ER stress and pyroptosis-related proteins. Furthermore, the inhibition of mitochondrial quality control by mdivi-1 significantly abolished the cardioprotective effect of irisin.

Our findings suggest that irisin reduced myocardial arrhythmia induced by I/R injury in diabetic rats by modulating the interaction of mitochondrial biogenesis and ER stress proteins and inhibiting the pyroptosis pathway. These findings provide a promising strategy for managing myocardial arrhythmia in diabetic patients, but supplementary studies are needed to confirm the clinical efficacy of irisin in these patients.

Ovarian torsion is an important gynaecological emergency because it causes ischemia in ovary. Our aim is to research the effects of Hypericum perforatum on p53, TNF-α, CAT, SOD, GSH, PTEN and is haPI3K/Akt/mTOR pathway in ovarian of rats with ischemia reperfusion (I/R) injury.

The study included 56 adult female rats which were allocated to 7 groups; control, ischemia, ischemia 300HP, ischemia 600HP, I/R, I/R 300HP and I/R 600HP. H. perforatum was applied to ischemia 300HP, ischemia 600HP, I/R 300HP and I/R 600HP groups at the dose of 300 mg/kg or 600 mg/kg by oral gavage. Collected ovarian tissues were examined by light microscopy, biochemical and real-time PCR techniques.

In histological examination, the least degeneration was seen in 600HP group among other groups, apart from control group. TUNEL results showed that apoptosis level of other groups was lower than that of ischemia and I/R groups. CAT and GSH levels of I/R 600HP group increased. The highest level of PTEN and mTOR was found in the ischemia group. The Akt level was lower in I/R and I/R 300HP groups but its level was close to that of control and I/R 600HP groups. TNF-α and p53 mRNA expressions in I/R group were increased.

The result of the study showed that H. perforatum (600 mg/kg) had an effect on tissue degeneration, CAT and GSH levels, and also TNF-α and p53 mRNA expressions levels. We suggest that H. perforatum can be considered as an agent to protect against tissues damage during ischemia reperfusion.

Hepatic ischemic post-conditioning (IPOC) is shown to protect the liver from injury induced by ischemia/reperfusion (IR). However, the mechanism underlying this protection has remained elusive. The present study aimed to investigate the role of the interleukin 6-Janus kinase-signal transducers and activators of transcription (IL-6-JAK-STAT) pathway in the protective effect of hepatic IPOC against the IR-induced injury in the liver.

Twenty-five rats were randomly divided into 5 groups of (1) sham-operated, (2) IR, (3) IR+hepatic IPOC, (4) IR+tofacitinib (TOFA), and (5) IR+TOFA+hepatic IPOC. The changes induced by IR and the effects of different treatments were assessed by enzyme release, histopathological observations, the serum level of IL-6, and the occurrence of apoptosis detected via the expression of the Bax/Bcl-2 ratio.

The hepatic IPOC improved the liver injury induced by IR as shown by histological changes, reduction of IL-6 level, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) compared to the IR group (P<0.001, P<0.05, P<0.05, respectively). There was also downregulation of the Bax/Bcl2 ratio in the rats exposed to IR+hepatic IPOC compared with those in the IR group (P<0.05). However, TOFA, an inhibitor of JAK-STAT activity, inhibited the protective effect of hepatic IPOC.

It suggests that the protective effect of hepatic IPOC against IR-induced injury may be mediated by activating the IL-6-JAK-STAT pathway.

Despite the unconditional success achieved in the treatment and prevention of AMI over the past 40 years, mortality in this disease remains high. Hence, it is necessary to develop novel drugs with mechanism of action different from those currently used in clinical practices. Studying the molecular mechanisms involved in the cardioprotective effect of adapting to cold could contribute to the development of drugs that increase cardiac tolerance to the impact of ischemia/reperfusion. An analysis of the published data shows that the long-term human stay in the Far North contributes to the occurrence of cardiovascular diseases. At the same time, chronic and continuous exposure to cold increases tolerance of the rat heart to ischemia/ reperfusion. It has been demonstrated that the cardioprotective effect of cold adaptation depends on the activation of ROS production, stimulation of the β2-adrenergic receptor and protein kinase C, MPT pore closing, and KATP channel.

Gum arabic (GA) contains anti-oxidant and anti-inflammatory compounds and protects tissues.

The purpose of the present study was to investigate the protective effect of GA on the spinal cord’s motor neurons after ischemia-reperfusion (I-R) injury.

Thirty-five male rats (Sprague-Dawley) were randomly divided into five groups: Intact, sham surgery, control (4 mL/kg distilled water+I/R), low-dose gum arabic (GA 1 g/kg+I-R), and high-dose gum arabic (GA 4 g/kg+I-R). In the experimental groups, oral gavages’ treatment was performed for 21 days before surgery. Three days after I-R, the rats were evaluated for neurological function, biochemical, and histological analysis.

The mean motor deficit index (MDI) in the GA groups versus the control group was significantly lower (P<0.01). About 72 hours after I-R, the mean plasma level of superoxide dismutase and total anti-oxidant capacity in the GA 4 g/kg group were higher than the control group (P<0.05). However, there was no significant difference in the plasma level of catalase between the GA 4 g/kg and the control groups (P<0.05). Approximately 67% of the motor neurons were destroyed in the control group, while this ratio was about 18% in the GA 4 g/kg group.

This study showed that GA (4 g/kg) protects the motor neurons of the spinal cord against ischemia-reperfusion injury.

Cerebral ischemia/reperfusion (I/R) has been known as a major cause of inability and mortality worldwide. Ellagic acid (EA) has many pharmacological effects including antioxidant, antithrombotic and neurorestoration activities. The aim of this study was evaluation of the effects of EA on motor and cognitive behaviors, hippocampal local field potential (LFP), brain oxidative stress in male rats with cerebral 2-vessel occlusion ischemia/reperfusion (2VO I/R). Forty-eight male Wistar rats (250-300 g) were assigned into six groups. 1) The Sham: rats were treated with DMSO10%/normal saline as solvent of EA 3 times daily for 1 week; 2) I/R+Veh; I/R rats received vehicle; 3-5) EA-treated groups: I/R rats received 50, 75, or 100 mg/kg EA; and 6) Cont+EA100: intact rats received EA. The cerebral 2VO I/R was made by the bilateral common carotid arteries closing for 20 min followed by reperfusion. The behavioral tests and hippocampal LFP recording were performed after treatment with EA. The oxidative stress parameters were assayed by special ELISA kits. Cerebral 2VO I/R significantly decreased motor coordination, memory and hippocampal LFP and significantly increased oxidative stress. Treatment with EA improved all I/R complications.  The current findings showed that treatment of I/R rats with EA could reverse cognitive and motor functions, and improve the LFP and oxidative stress markers. So, effects of EA on cognitive and motor function may at least in part, be due to its antioxidative actions.

Ovarian ischemia/reperfusion (I/R) is an extremely complex pathological problem that begins with oxygen deprivation, progresses to excessive free radical production, and intensifies inflammation. The JAK2/STAT3 signaling pathway is a multipurpose signaling transcript channel that plays a role in several biological functions. Trimetazidine (TMZ) is a cellular anti-ischemic agent. This study aims to investigate the effects of TMZ on ovarian I/R injury in rats. sixty four rats were divided into 8 groups at random: healthy(group1); healthy+TMZ20(group2); ischemia (I) (group 3); I+TMZ10(group4); I+ TMZ20(group5); I/R(group6); I/R+TMZ10(group7); I/R+TMZ20(group8). Vascular clamps were placed just beneath the ovaries and over the uterine horns for 3 hr to induce ischemia. The clamps were removed for the reperfusion groups, and the rats were reperfused with care to ensure that the blood flowed into the ovaries, subjecting them to reperfusion for 3 hr. TMZ was administered orally by gavage 6 and 1 hr before operations. At the end of the experiment, ovarian tissues were removed for biochemical, molecular, and histopathological investigation. TMZ administration ameliorated ischemia/reperfusion-induced disturbances in GSH and MDA levels. TMZ treatment inhibited I/R-induced JAK2/STAT3 signaling pathway activation in ovarian tissues. TMZ administration also improved the increase in the mRNA expressions of IL-1β, TNF-α, and NF-κB caused by ischemia/reperfusion injury. Moreover, TMZ treatment improved histopathologic injury in ovarian tissues caused by ischemia/reperfusion. TMZ treatment protected rats against ovarian ischemia/reperfusion injury by alleviating oxidative stress and inflammatory cascades. These findings may provide a mechanistic basis for using TMZ to treat ovarian ischemia-reperfusion injury.

 Apoplexy is known as a critical issue all over the world and certain parts of the brain are more sensitive to Ischemia/cerebral reperfusion such as the hippocampus. Coenzyme Q10 is a powerful anti-oxidant, which helps in cells membrane durability.

 This study attempts to find the effect of coenzyme Q10 on the change of hippocampal area texture after cerebral reperfusion/Ischemia.                                                                                                                               

 Twenty-four male Wistar rats were organized into 4 groups of six including control, Ischemia, vehicle and experimental groups, with 100 mg /Kg of coenzyme Q10. Coenzyme Q10 was given to the rats 5 days before and 3 days after Ischemia/reperfusion induction. Ischemia was done for 20 minutes by reciprocal blocking of carotid arteries. The rat’s brains were removed and stained by applying the chrysalis fast violet method. The number of viable cells of the hippocampal regions of all 4 groups was counted by Imaging-Pro-Plus software. Statistical analysis of the data was then accomplished by one-way ANOVA and Tukey's test.

 Findings revealed that the number of viable cells in CA2 and CA3 area reduced following ischemia induction. Whereas, there was no notable change between the control and experimental groups in terms of cells numbers. Besides, there was no remarkable change between the control, experimental and ischemia groups in terms of the number of cells within CA4 area.

 The results support the use of coenzyme Q10 as a neurotrophic substance and as an adjunctive therapy in patients at risk for ischemic stroke.

The renin-angiotensin system activation, partial ischemia/reperfusion (IR) injury, and hypertension contribute to the development of acute kidney injury. The study aims to look at the vascular responses of angiotensin II (Ang II) during Ang II type 1 receptor (AT1R) blockade (losartan) or co-blockades of AT1R and Mas receptor (A779) in two kidneys one clip (2K1C) hypertensive rats which subjected to partial IR injury with and without ischemia preconditioning (IPC).

Experimental approach: 

Thirty-three 2K1C male Wistar rats with systolic blood pressure ≥ 150 mmHg were divided into three groups of sham, IR, and IPC + IR divided into two sub-groups receiving losartan or losartan + A779. The IR group had 45 min partial kidney ischemia, while the IPC + IR group had two 5 min cycles of partial ischemia followed by 10 min of reperfusion and then 45 min of partial kidney ischemia followed by reperfusion. The sham group was subjected to similar surgical procedures except for IR or IPC.

Ang II increased mean arterial pressure in all the groups, but there were no significant differences between the sub-groups. A significant difference was observed in the renal blood flow response to Ang II between two sub-groups of sham and IR groups treated with AT1R blockade alone or co-blockades of AT1R + A779.

Conclusion and implications: 

These findings demonstrated the significance of AT1R and Mas receptor following partial renal IR in the renal blood flow responses to Ang II in 2K1C hypertensive rats.

 Inflammation, oxidative stress, and cell death are major contributors to kidney injury following ischemia/reperfusion (I/R). Acacetin (ACA) is a natural flavonoid that many studies have shown can prevent I/R-induced damaging effects.

 In the current attempt, we sought to search for the mechanisms through which ACA attenuates renal I/R.

 Male Balb/c mice were divided into four groups (n = 7): sham-operated group, I/R group, I/R treated with 50 mg/kg ACA group, and control group. Following 60 min ischemia, reperfusion was performed for 24 h. Administrations were done intraperitoneally daily for four consecutive days. Renal function was evaluated by measurement of creatinine. Changes in antioxidant capacity were evaluated by superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. The expression of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-18 (IL-18), heme oxygenase-1 (Ho-1), nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), and thioredoxin 1 (Trx1) was detected by real-time reverse transcription polymerase chain reaction (real-time RT-PCR). The levels of IL-10, tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2) were detected by enzyme-linked immunosorbent assay (ELISA) assay.

 Creatinine level showed a decreased value after ACA treatment; however, declined SOD and GPx activities were elevated by ACA. The increased expression of IL-1β, IL-6, and IL-18 in the I/R group was declined in ACA-receiving mice. The expression levels of genes involved in anti-oxidative response Nrf-2, Ho-1, and Trx1 were decreased remarkably in the I/R group, and it reversed in ACA-treated mice. The secretion of IL-10 was elevated in the ACA-administrated group compared to untreated animals, while the COX-2 and TNF-α proteins were decreased following ACA treatment.

 These beneficial effects of ACA suggest that oxidative stress response participates in the protective effect of ACA against renal I/R.