An Overview of Ischemia-Reperfusion Injury: Review on Oxidative Stress and Inflammatory Response.

Ischemia-reperfusion is a common health problem leading to several health conditions. The pathophysiology of ischemia-reperfusion is quite complex. Oxidative stress and inflammatory response contribute to ischemia-reperfusion mechanisms. Various parameters like proinflammatory cytokines, reactive oxygen species, occur during ischemia-reperfusion . There are several ways to investigate these values through biochemical and histopathologic findings. Malondialdehyde, glutathione, myeloperoxidase, superoxide dismutase, interleukin 6, interleukin 1ß, tumor necrosis factor alpha, caspase-3, nuclear factor-kappa ß, and LC3B (microtubu le-associated protein light chain 3, LC3) can be evaluated among these indicators.

Protective effects of gallic acid on doxorubicin-induced cardiotoxicity; an experimantal study.

The present study aims to examine the possible beneficial effects of gallic acid (GA) against doxorubicin-induced cardiotoxicity in the experimental model. Rats were weighed and divided into groups. Groups as following; control, gallic acid (GA), doxorubicin (DOX) and GA + DOX groups. At the end of the experiment, rats were sacrificed and heart tissue removed. The tissues were analysed in terms of biochemical (MDA, SOD, CAT, GSH, GPx), pathological (hyaline degeneration, Zenkerin necrosis, hyperaemia) and immunohistochemical (TNF-α, Cox-2). MDA level decreased and antioxidant enzyme activities increased in GA + DOX group compared to doxorubicin group. TNF-α, Cox-2 expression levels were severe in the DOX group. Also, pathologic tissue damage in heart tissue increased due to doxorubicin. Additionally, pathologic tissue damage and TNF-α, Cox-2 expression levels decreased in GA + DOX group. According to our findings, GA has protective effect against doxorubicin-induced cardiotoxicity.

Levosimendan ameliorates cisplatin-induced ototoxicity: Rat model.

OBJECTIVES: Cisplatin is employed for chemotherapeutic purposes in several types of adult and pediatric cancer. However, side-effects including nephrotoxicity, ototoxicity, gastrointestinal effects and neuropathy restrict the use of the drug due to their adverse impacts on quality of life. This study aimed to determine whether levosimendan exhibits a protective effect against cisplatin-related ototoxicity in a rat model by means of functional, biochemical and histochemical analysis. METHODS: The study was employed with 24 female Sprague Dawley rats. After distortion product otoacoustic emissions (DPOAE) tests applied to all rats, rats were randomly assigned into four groups of six animals each. A single intraperitoneal 15 mg/kg dose of cisplatin was administered to Cisplatin group. Levosimendan group received intraperitoneal levosimendan at a dose of 100 mg/kg for five consecutive days. Cisplatin + Levosimendan group received intraperitoneal levosimendan at a dose of 100 mg/kg for five consecutive days and a single intraperitoneal dose of 15 mg/kg cisplatin at 3rd day of the study. Control group received 8 mL/kg/day intraperitoneal saline solution for five consecutive days. The DPOAE test was repeated on the 6th day of the study. All rats were then sacrificed, the cochleas were removed and set aside for biochemical and histopathological analyses. RESULTS: A significant increase in levels of Malondialdehyde (MDA) and significantly lower activities of superoxide dismutase (SOD) and Glutathione peroxidase (GPx) were observed at rats of cisplatin group. Administration of levosimendan showed significantly lower cochlear MDA levels, while SOD and GPx activities both increased significantly. The DPOAE test performed at 6th day of the study showed a significant impairment in the signal-noise ratio (SNR) levels of rats in Cisplatin group. The SNR levels of rats treated with levosimendan were significantly higher than those of cisplatin group and were similar to those of the control group. Cisplatin impaired the cochlear structure and a severe Caspase 3 and 8-hydroxy-2' -deoxyguanosine (8-OHdG) immunopositivity was observed at cochlea of the rats of cisplatin group. Administration of levosimendan protected the structure of cochlea and there was a mild Caspase 3 and 8OHdG immunopositivity. CONCLUSION: Our data demonstrate that levosimendan protects hearing against cisplatin-induced ototoxicity and obviates cellular degeneration. It also significantly reduces oxidative stress and apoptosis, probable mechanisms involved in ototoxicity.

Anti-oxidant and anti-inflamatuar effectiveness of caftaric acid on gastric ulcer induced by indomethacin in rats.

In this study, we evaluated the anti-oxidant and anti-inflammatory effect of caftaric acid against ulcer produced by indomethacin in gastric mucosa. Female Sprague Dawley albino rats were divided into five groups: control (saline group, n = 8), negative control (indomethacin group, n = 8), positive control (omeprazole group, n = 8), low dose therapy (caftaric acid, n = 8), and high dose therapy (caftaric acid, n = 8). At the end of the experiment, all rats were sacrificed and gastric mucosa samples were removed for macroscopic and biochemical analysis. In our study, we detected that oxidant parameter values and cytokine levels increased in the negative control group, but total antioxidant status reduced, whereas, cytokine and oxidant parameter levels were significantly reduced due to low and high doses of caftaric acid administration. But another important point to note is that high dose caftaric acid therapy performed gastroprotective effect as omeprazole. In the macroscopic evaluation, there were reductions in ulcer sizes with a low and high dose of caftaric acid administration in contrast to the negative control group. As a result of our study, caftaric acid showed anti-oxidant and anti-inflammatory effects in indomethacin-induced gastric ulcer in rats.

The Protective Effects of p-Coumaric Acid on Acute Liver and Kidney Damages Induced by Cisplatin.

In this study, we aimed to investigate the effects of p-Coumaric acid (PCA) on cisplatin (CIS)-induced hepatotoxicity and nephrotoxicity in Wistar adult rats for 24 h compared to untreated control groups. In this experiment, 40 Wistar adult rats were utilized and divided randomly into five groups. After 24 h of CIS administration, liver and kidneys were harvested and assessed by H&E staining. Also, markers for oxidative stress and antioxidants were analyzed in theses tissues. Compared to the control group, accumulation of malondialdehyde was increased in groups treated CIS, whereas superoxide dismutase activities and glutathione levels were distinctly diminished in this group. The study's histopathological findings such as hydropic degeneration, vascular congestion, sinusoidal dilatation in hepatocytes and tubular necrosis in kidneys were in accordance with the results of markers for oxidative stress. PCA may prevent hepatotoxicity and nephrotoxicity by increased antioxidant enzymes and reduced oxidant parameters.

A comparative study on the antioxidant effects of hesperidin and ellagic acid against skeletal muscle ischemia/reperfusion injury.

The antioxidant effects of ellagic acid (EA) and hesperidin (HES) against skeletal muscle ischemia/reperfusion injury (I/R) were performed. Hindlimb ischemia has been induced by tourniquet occlusion for 2 h on left hindlimb. At the end of ischemia, the tourniquate has been removed and initiated reperfusion for 2 h. EA (100 mg/kg) has been applied orally before ischemia/reperfusion in the EA + I/R group. HES (100 mg/kg) has been given orally in the HES + I/R group. The left gastrocnemius muscle has been harvested and stored immediately at -80 °C until assessed for the levels of MDA and antioxidant enzymes activities. MDA level has statistically increased in I/R group (p < 0.05) compared to other groups. The muscle tissue antioxidant enzymes activities were lower than the other groups in the I/R group (p < 0.05). EA and HES treatments significantly reversed the damage level in I/R, also activity of tissue SOD increased in the EA + I/R and HES + I/R groups.

Quercetin protects rat skeletal muscle from ischemia reperfusion injury.

In this study, we investigated the potential beneficial effects of quercetin on skeletal muscle ischemia reperfusion injury. Twenty-four Sprague-Dawley type rats were randomly divided into four groups. In the sham group, only gastrocnemius muscle were removed and given no quercetin. In ischemia group, all the femoral artery, vein and collaterals were occluded in the left hindlimb by applying tourniquate under general anaesthesia for three hours but reperfusion was not done. In the Quercetin + Ischemia reperfusion group, quercetin (200 mg kg-1 dose orally) was given during one-week reoperation and later ischemia reperfusion model was done. Finally, gastrocnemius muscle samples were removed to measure biochemical parameters. The biomarkers, MDA levels, SOD, CAT and GPx activities, were evaluated related to skeletal muscle ischemia reperfusion injury. MDA levels reduced and SOD, CAT and GPx activities increased significantly in Quercetin + Ischemia reperfusion group. Results clearly showed that Quercetin have a protective role against oxidative damage induced by ischemia reperfusion in rats.

Protective effect of Naringin on experimental hindlimb ischemia/reperfusion injury in rats.

This study was designed to investigate the antioxidant effects of Naringin, in ischemia/reperfusion (I/R)-induced skeletal muscle injury in rats. The rats were randomly allocated into three groups including control, I/R and I/R + Naringin groups. Muscle tissues of I/R groups revealed significantly higher antioxidant enzyme activities, and increased levels of malondialdehyde, as specific a marker of the lipid peroxidation and tissue damage, compared to the control group (p < 0.05). Levels of these parameters in muscle revealed significant reductions in the I/R + Naringin group compared to the I/R group (p < 0.05). Histopathological examination of ischemia muscles in the I/R group showed significant degeneration and inflammation compared to the control group, whereas ischemic muscles of Naringin-administered group showed significant reduction in degeneration and inflammation compared to the I/R group (p < 0.05). We suggest that the protective effect of Naringin may reduce the I/R injury in cases of extremity injuries with acute vascular complications, extremity surgery with prolonged tourniquet application.