ischemia-reperfusion

 Testicular torsion is an emergency urological condition characterized by the twisting of the spermatic cord, leading to restricted blood flow to the testes and ultimately resulting in testicular atrophy. Ischemia-reperfusion (I/R) injury caused by testicular torsion induces apoptosis in germ cells and disrupts spermatogenesis, leading to testicular damage. Hydrogen sulfide (H₂S), due to its anti-inflammatory, antioxidant, and anti-apoptotic properties, provides protective effects and may serve as a potential therapeutic option to mitigate infertility disorders associated with testicular ischemia. As a result, the aim of the present study was to determine and investigate the protective effect of hydrogen sulfide on testicular injury induced by ischemia-reperfusion in Wistar rats.

In the present experimental study conducted in 2021 at Bu Ali Sina University, hamadan, 32 male Wistar rats were divided into four groups: Group 1 (control), Group 2 (ischemia-reperfusion), Group 3 (ischemia-reperfusion with hydrogen sulfide administration, 100 µg/kg intraperitoneally), and Group 4 (ischemia-reperfusion with hydrogen sulfide administration, 400 µg/kg intraperitoneally). After 72 hours, the animals were euthanized, and their testes and epididymides were removed for histological examination. The number, viability, and morphology of epididymal sperm were analyzed. Data were statistically analyzed using one-way ANOVA followed by Tukey's post hoc test in Prism software.

The results indicated that testicular I/R injury significantly reduced testicular (0.48) and epididymal indices (0.21)(p<0.001), as well as the number (318x106) and viability (26%)(p<0.001)  of epididymal sperm. Additionally, abnormal sperm morphology increased significantly following unilateral testicular I/R (91%)(p<0.001). Administration of hydrogen sulfide significantly improved the number (450x106)(p<0.001), viability (61%)(p<0.05), and morphology of epididymal sperm (44%)(p<0.05) and reduced tissue damage compared to the I/R group.

The results of this study revealed that treatment with hydrogen sulfide in a dose-dependent manner improves sperm parameters and reduces tissue damage in testis ischemia-reperfusion model. Therefore, treatment with hydrogen sulfide can be considered as a treatment method to reduce complications caused by testicular ischemia-reperfusion.

This study investigated the effect of S-ketamine administration as a neuroprotective treatment for necrotic cell death and memory and learning impairments following a cerebral ischemia model in male rats.

In this experimental study, 28 male Wistar rats with weighing between 250-300 g, were randomly divided into four groups: Sham, Ischemia-Saline, Ischemia-S-ketamine (low dose), and Ischemia-S-ketamine (high dose).In the ischemia groups receiving low and high doses of S-ketamine, the drug was administered immediately right after the onset of ischemia at doses of 0.1 mg/kg and 0.25 mg/kg body weight, respectively. Memory and learning were evaluated in the different groups through the passive avoidance learning test. Four days after induction of ischemia, necrotic cell death was measured using Cresyl violet staining. Data were analyzed using SPSS software.

The results showed that in the ischemia-saline group, significantly increased in the number of necrotic cells compared to the sham group (p<0.05). Treatment with S-ketamine substantially decreased necrotic cell death in the CA1 region of the hippocampus. The reduction in ischemia-induced cell death was more significant in the high-dose S-ketamine treatment group compared to the low-dose S-ketamine treatment group (p<0.05). Moreover, S-ketamine treatment improved memory and learning deficits caused by ischemia in a dose-dependent manner.

Treatment with S-ketamine has been able to affect the consequences of cerebral ischemia, and therefore the introduction of S-ketamine therapy is proposed as a new therapeutic method in the treatment of cerebral ischemia.

Renal ischemia-reperfusion injury (IRI) is one of the inevitable complications of surgery. The evidence shows that fingolimod, with its anti-inflammatory effects, can play a protective role in renal IRI. The main aim of the present study was to investigate the role of fingolimod against renal IRI in the heart tissue.

Twenty-four male Wistar rats (220±20g) were treated with a single dose of fingolimod (1mg/kg) by intraperitoneal injection before the induction of kidney IRI. At the end of the reperfusion period, the oxidative stress biomarker (malondialdehyde) and antioxidant biomarkers (catalase, superoxide dismutase, glutathione, glutathione peroxidase, and total antioxidant capacity) were evaluated in the heart tissue.

Fingolimod pretreatment could increase cardiac glutathione enzyme activity in the fingolimod+IR group compared to the IR group, which was not statistically significant (P>0.05). The level of total antioxidant capacity in the heart tissue was also significantly increased in the fingolimod+IR group in comparison to the IR group (P<0.05).

Fingolimod was able to prevent oxidative stress damage in the heart caused by kidney IR induction by increasing the level of total antioxidant capacity of the heart tissue. It is suggested that future studies evaluate the effects of this drug in clinical trials.

The total antioxidant capacity of the heart, as a distant organ affected by kidney IRI, is increased following fingolimod pre-treatment.

Renal ischemia-reperfusion (IR) damage occurs during renal transplantation in end-stage renal disease (ESRD) patients which activate immune responses. Inflammatory responses by increased levels of cytokines can lead to acute kidney injury (AKI) that contributes to the loss of renal grafts and graft dysfunction. The purpose of this study was to review the therapeutic effects of nanoparticles in AKI.

A comprehensive search strategy was identified relevant studies on AKI models, using the Scopus, PubMed and Google Scholar databases, from 2000 until 2020. The search strategy included keywords like ischemia-reperfusion and nanoparticles.

Oxygen free radicals are produced during the reperfusion phase, which cause lipid peroxidation and promote tissue damage. Oxidative damage to DNA and proteins and lipid membrane peroxidation can cause cell death and apoptosis. Some strategies to reduce the tissue damage caused by ischemia-reperfusion are nanoscale materials. Antioxidant nanoparticles reduce oxidative stress in tissues. Also, they have flexibility in the delivery of therapeutic agents and drugs to the ischemic cells, and imaging of the ischemic regions at the molecular or cellular level.

This potential of antioxidant and anti-inflammatory nanoparticles in the diagnosis and treatment of renal ischemic regions is an innovation in the development of new therapies and a unique achievement in recent medical advances.

Cerebral ischemia-reperfusion causes complex pathological mechanisms that lead to tissue damage, such as neuronal apoptosis. Usnic acid is a secondary metabolite of lichen and has various biological properties including antioxidant and anti-inflammatory activities. This study aimed to investigate the neuroprotective effects of usnic acid on apoptotic cell death and apoptotic-related proteins (Bax and Bcl-2) in the CA1 area of the hippocampus following cerebral ischemia-reperfusion.

A total of 42 male Wistar rats were randomly divided into three groups (sham, ischemia-reperfusion, and ischemia-reperfusion+usnic acid). Ischemia was induced by occlusion of both common carotid arteries for 20 min. Usnic acid (25 mg/kg, intraperitoneally) was injected at the beginning of reperfusion time. The expression levels of Bax and Bcl-2 proteins were measured using the immunofluorescence method, and the rate of apoptotic cell death was determined using the TUNEL staining method.

In this study, cerebral ischemia increased apoptotic cell death in the CA1 area of the hippocampus. It was demonstrated that usnic acid significantly decreased apoptotic cell death by decreasing the expression of Bax pro-apoptotic protein and increasing the expression of Bcl-2 (anti-apoptotic protein).

It can be concluded that usnic acid has a neuroprotective effect against cerebral ischemia-reperfusion damages by reducing cell death.

Diabetes is one of the major risk factors for ischemic heart disease. The aim of this study was to investigate the effect of antioxidant drug troxerutin (TXR) on ischemia-reperfusion-induced myocardial injury in experimental streptozotocin-induced diabetic rats.

Male Wistar rats (250-270 g) were divided into four groups including control, troxerutin, streptozotocin and streptozotocin + troxerutin groups. Diabetes was induced in the rats by intraperitoneal injection of 50 mg / kg streptozotocin and rats were studied for 10 weeks. Rats in the streptozotocin + tezroxerotin group received troxerotin by oral gavage for 4 weeks from the 7th week onwards. The hearts of the rats in all groups were placed in the Langendrov apparatus after separation from the body and subjected to local ischemia for 30 minutes followed by reperfusion for 60 minutes. The amount of lactate dehydrogenase enzyme in coronary artery as well as the parameters of superoxide dismutase and glutathione peroxidase in myocardial tissue during ischemia-reperfusion were measured using special kits.

Body weight and the amount of superoxide dismutase and glutathione peroxidase enzymes were significantly decreased in the diabetic rats (P <0.05). Troxerutin in the streptozotocin + troxerutin group improved the levels of these enzymes to normal levels (P <0.05), whereas lactate dehydrogenase level decreased in this group (P <0.05).

In this study troxerutin reduced the severity of ischemia-reperfusion injury in the diabetic rats.

One of the most important causes of acute kidney injury is ischemia-reperfusion (IR). Some studies have shown that adenosine A1 receptor inhibition have protective effects against Ischemia–reperfusion induced renal injuries, while other studies have demonstrated the opposite. The aim of the present study was to review the methodology of these studies to reach a final conclusion about the effects of adenosine A1 receptor on ischemia-reperfusion-induced renal injuries.

Data base motors including Scopus, PubMed, Google Scholar, Science Direct and Embase were searched. The terms and keywords used included ischemia-reperfusion, acute kidney injury, acute renal failure, A1 adenosine receptor and their combination.

Increased adenosine levels following renal Ischemia-reperfusion cause vasoconstriction in afferent arteriole and vasodilatation in efferent arteriole through A1 adenosine receptor activation, which in turn reduces glomerular filtration rate (GFR). Inhibition of A1 adenosine receptor leads to short-term correction of renal functional parameters following renal Ischemia-reperfusion, by increasing renal blood flow and thus improving GFR. But this increase in GFR exacerbates kidney damages through the kidneys workload enhancement, which will show up in the next few hours.

Although selective inhibition of A1 adenosine receptor in the short term improves renal function parameters, but exacerbates renal damages in the following hours. Therefore, adenosine A1 receptor stimulation has protective effects against IR-induced kidney injury.

Renal ischemia-reperfusion is known as the underlying pathophysiology of a variety of severe clinical disorders, such as acute renal failure. The use of antioxidants is one of the most important treatment strategies to reduce the ischemia-reperfusion induced injury due to the importance of reactive oxygen species and oxidative stress during ischemia reperfusion. Salvia spices, especially Salvia macrosiphon Boiss, are rich in antioxidant compounds. The present study aimed to investigate the protective effects of these substances on renal ischemia reperfusion.

In this study, 42 Wistar rats were divided into six groups of seven animals per group. The groups included a sham, a control, and four treatments. One of the treatment groups was treated with luteolin, and the other three groups were treated with different concentrations (50, 100, 150 mg/kg) of Salvia macrosiphon Boiss methanolic extract for 20 days before ischemia. After 24 hours following ischemia, blood samples were taken from the rats, and their serum creatinine and urea levels were evaluated.

Salvia macrosiphon Boiss extract (at the dose of 100 mg/kg) significantly reduced urea and creatinine levels (P<0.001). Moreover, Luteolin decreased both ceratinine (P<0.01) and urea (P<0.05) levels.

This study confirmed the positive and significant effect of Salvia macrosiphon Boiss extract and Luteolin on the studied factors. The observed effect could be in part due to the potential antioxidant properties of flavonoids and methanol extract of Salvia macrosiphon Boiss.

Oxidative stress and inflammation increase after eccentric exercise. Cold-water immersion after exercise is common among athletes to accelerate recovery. Therefore, the purpose of this study was to investigate the effect of cold-water immersion after eccentric exercise on the oxidative and inflammatory responses in skeletal muscle.

One hundred male Wistar rats (weight 285.11 ± 41.65) were randomly divided into control, eccentric exercise, eccentric exercise + normal water, and eccentric exercise + cold water groups. Half, 24, 48, 72, and 168 hours after eccentric exercise, EDL muscle was removed in sterile conditions. The eccentric exercise involves 90 minutes of interval running on the treadmill at a speed of 16 m/min and a -16-degree slope. Muscle reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-α) levels were measured by DCFDA and immunohistochemical staining. Kolmogorov-Smirnov for normality test and repeated measure ANOVA and Tukey’s post-Hoc tests for compare groups were used with a significance level of P≤0.05.

After eccentric exercise, ROS and TNF-α levels significantly (P<0.05) increased in the three experimental groups. The peak of ROS increase in the eccentric exercise, eccentric exercise + normal water, and eccentric exercise + cold water groups were recorded significantly (P<0.001) half, 48, and 72 hours after eccentric exercise, respectively. Also, the peak of TNF-α increase was significantly higher in the eccentric exercise and eccentric exercise + normal water groups were at 48 hours and in the eccentric exercise + cold water groups was at 72 hours after eccentric exercise (P<0.001).

Immersion in cold water causes an increase and delays the peak of ROS and TNF-α after eccentric exercise, which is probably related to ischemia-reperfusion injury. Therefore, after unaccustomed, eccentric, and damaging exercise, immersion in cold water is not recommended.

Renal ischemia/reperfusion injury is one of the major causes of acute renal failure. This study aimed to investigate the effects of gamma oryzanol administrated by gavage and intraperitoneal methods on the antioxidant function and status of the kidneys and brain tissue after the induction of ischemia-reperfusion injury in the kidneys of rats.

The statistical population of this study consisted of 24 male rats divided into four 6-member groups, including the sham group without ischemia, control group with ischemia-reperfusion induction, ischemia-reperfusion group receiving treatment with 100 mg/body weight intraperitoneally, and ischemia-reperfusion group administered with a dose of 100 mg/body weight by gavage method. Gamma oryzanol was administered 1 h followed by the onset of left renal ischemia for 30 min. After 6 h of reperfusion, blood creatinine and urea and antioxidant function of the kidneys and brain tissue were measured.

The results showed that the administration of gamma oryzanol by both methods of intraperitoneal injection and gavage caused a significant reduction in creatinine and blood urea levels, compared to the control group (P<0.05). Moreover, the amounts of glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, and total oxidant capacity of kidney and brain tissue were significantly increased in the groups receiving treatment with gamma oryzanol; however, malondialdehyde level was significantly reduced in the same group, compared to the control group (P<0.05).

Based on the results, gamma oryzanol improved renal function and reduced the negative severity of ischemia-reperfusion injury in renal and brain tissues. It was also found that the gavage method performed better than the intraperitoneal injection method.

Exercise training cited as the most important non-pharmacological strategy to cardio-protective effects of preconditioning, but the molecular mechanism of this process is not yet clear. Therefore, in this study, we evaluated the cardio-protective effects of swimming training Preconditioning on Ischemia Reperfusion-Injury in male Wistar rats.

For this purpose, 20 male Wistar rats were randomly divided into control and training groups. The training group performed swimming training for 10 weeks (5 days per week, each session 60 min). All subjects underwent myocardial ischemia (30 min) reperfusion (120 min) surgery after intervention. Then, infarction size and oxidative stress indices were measured.

Statistical analyses showed that antioxidant indices GSH, GPx and Catalase induced-myocardial ischemia reperfusion were not different between groups, but MDA and MPO were significantly lower in the training group than in the control group. Also, infarction size area following ischemia reperfusion in the training group (34.32±6.4) was 8% less than the control group (42.17±9.7). 

The results of this study showed that ten weeks of swimming training reduced the size of the infarcted area after myocardial ischemia-reperfusion injury by reducing free radical production. These changes suggest protective preconditioning effects of swimming exercises.