The Effect of "Proanthocyanidin" on Ischemia-Reperfusion Injury in Skeletal Muscles of Rats.

Background and Objectives: Lower limb skeletal muscle ischemia-reperfusion (IR) injury is associated with increased morbidity and mortality, and it is common in several clinical situations such as aortic aneurysms repairment, peripheral arterial surgery, vascular injury repairment, and shock. Although it is generally accepted that oxidative stress mediators have a significant role in IR injury, its precise mechanism is still unknown. Anecdotally, it is sustained not only by structural and functional changes in the organ it affects but also by damage to distant organs. The purpose of this report is to illustrate the effect of proanthocyanidin on IR injury. Materials and Methods: In our study, 18 male Wistar albino rats were used. The subjects were divided into three groups containing six mice each (control, C; ischemia-reperfusion, IR; ischemia-reperfusion and proanthocyanidin; IR-PRO). Intraperitoneal proanthocyanidin was given to the IR and proanthocyanidin groups 30 min before laparotomy, and 1 h ischemia led to these two groups. After one hour, reperfusion started. Muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, muscle oval-central nucleus ratio, leukocyte cell infiltration, catalase enzyme activity, and TBARS were all examined in lower-limb muscle samples after one hour of reperfusion. Results: When skeletal muscle samples were evaluated histopathologically, it was discovered that muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, and leukocyte cell infiltration with oval-central nucleus standardization were significantly higher in the IR group than in the C and IR-P groups. Oval-central nucleus standardization was significantly higher in the IR and IR-PRO groups than in the control group. TBARS levels were significantly higher in the IR group than in the control and IR-PRO groups, while catalase enzyme activity was found to be significantly lower in the IR group than in the control and IR-PRO groups. Conclusions: As a consequence of our research, we discovered that proanthocyanidins administered before IR have a protective impact on skeletal muscle in rats. Further research in this area is required.

Effects of cerium oxide (CeO2) on liver tissue in liver ischemia-reperfusion injury in rats undergoing desflurane anesthesia.

INTRODUCTION: During liver surgery and transplantation, periods of partial or total vascular occlusion are inevitable and result in ischemia-reperfusion injury (IRI). Nanomedicine uses the latest technology, which has emerged with interdisciplinary effects, such as biomedical sciences, physics, and engineering, to protect and improve human health. Interdisciplinary research has brought along the introduction of antioxidant nanoparticles as potential therapeutics. The goal of this study was to investigate the effects of cerium oxide (CeO2) administration and desflurane anesthesia on liver tissue in liver IR injury. MATERIAL AND METHODS: Thirty rats were randomly divided into five groups: control (C), ischemia-reperfusion (IR), IR-desflurane (IRD), cerium oxide-ischemia reperfusion (CeO2-IR), and cerium oxide-ischemia reperfusion-desflurane (CeO2-IRD). In the IR, IRD, and CeO2-IRD groups, hepatic ischemia was induced after the porta hepatis was clamped for 120 min, followed by 120 min of reperfusion. Intraperitoneal 0.5 mg/kg CeO2 was administered to the CeO2 groups 30 min before ischemia. Desflurane (6%) was administered to the IRD and CeO2-IRD groups during IR. All groups were sacrificed under anesthesia. Liver tissue samples were examined under a light microscope by staining with hematoxylin-eosin (H&E). Malondialdehyde (MDA) levels, catalase (CAT), glutathione-s-transferase (GST), and arylesterase (ARE) enzyme activities were measured in the tissue samples. RESULTS: The IR group had considerably more hydropic degeneration, sinusoidal dilatation, and parenchymal mononuclear cell infiltration than the IRD, CeO2-IR, and CeO2-IRD groups. Catalase and GST enzyme activity were significantly higher in the CeO2-IR group than in the IR group. The MDA levels were found to be significantly lower in the IRD, CeO2-IR, and CeO2-IRD groups than in the IR group. CONCLUSION: Intraperitoneal CeO2 with desflurane reduced oxidative stress and corrected liver damage.

A dual-acting aldose reductase inhibitor impedes oxidative and carbonyl stress in tissues of fructose- and streptozotocin-induced rats: comparison with antioxidant stobadine.

Inhibiting aldose reductase (ALR2, AR) as well as maintaining a concomitant antioxidant (AO) activity via dual-acting agents may be a rational approach to prevent cellular glucotoxicity and at least delay the progression of diabetes mellitus (DM). This study was aimed at evaluating the dual-acting AR inhibitor (ARI) cemtirestat (CMTI) on tissue oxidative stress (OS) and carbonyl stress (CS) biomarkers in rats exposed to fructose alone (F) or fructose plus streptozotocin (D; type-2 diabetic). D and F rats were either untreated or treated daily with low- or high-dose CMTI, ARI drug epalrestat (EPA) or antioxidant stobadine (STB) for 14 weeks. Malondialdehyde (MDA), glutathione S-transferase (GST), nitric oxide synthase (NOS), and catalase (CAT) were increased in the sciatic nerve of F and D. These increases were attenuated by low doses of CMTI and STB in D, but exacerbated by low-dose EPA and high-dose CMTI in F. STB and CMTI and to a lesser extent EPA improved MDA, protein-carbonyl, GST and CAT in the hearts and lungs of F and D. CMTI and STB were more effective than EPA in improving the increased MDA and protein-carbonyl levels in the kidneys of F and especially D. CMTI ameliorated renal GST inhibition in D. In the lungs, hearts, and kidneys of F and D, the GSH to GSSG ratio decreased and caspase-3 activity increased, but partially resolved with treatments. In conclusion, CMTI with ARI/AO activity may be advantageous in overcoming OS, CS, and their undesirable consequences, with low dose efficacy and limited toxicity, compared to ARI or antioxidant alone.

The role of neuropeptide Y, orexin-A, and ghrelin in differentiating unipolar and bipolar depression: a preliminary study.

BACKGROUND: When depressive symptoms in bipolar and unipolar patients were compared, a number of studies reported that atypical vegetative features such as hypersomnia and hyperphagia were more common in bipolar patients. Moreover, neuropeptides such as orexin-A (ORX-A), ghrelin (GRL), and neuropeptide Y (NPY) are involved in the regulation of these vegetative functions. MATERIALS AND METHODS: A total of 45 unipolar and 24 bipolar depressive patients, and 36 euthymic healthy controls were included in the study. The groups were compared in terms of peripheral blood samples of ORX-A, GRL, and NPY levels, as well as HAM-D, Epworth Sleepiness Scale, Three-Factor Eating Questionnaire-Revised, and Suicide Probability Scale scores. RESULTS: Both unipolar and bipolar patients had lower ORX-A, GRL, and NPY levels compared to the controls, whereas NPY levels of bipolar patients were lower than unipolar patients. There was a negative correlation between NPY levels and emotional eating in the bipolar group. CONCLUSION: While lower ORX-A, GRL, and NPY levels are associated with depressive episodes regardless of the diagnosis; NPY levels also differ in bipolar and unipolar depression patients.

Investigation of oxidative stress status in cumulus cells in patients with in vitro fertilization

Background/aim: The negative impact of oxidative stress on oocytes obtained from in vitro fertilization (IVF) patients is a challenge for the optimization of live birth rates. In this study, it is aimed to investigate whether oxidant/antioxidant parameters have a predictive value in terms of determining the count and quality of oocytes. Materials and methods: Catalase (CAT), glutathione-S-transferase (GST), arylesterase (ARE) enzyme activities, and malondialdehyde (MDA) levels were analysed in cumulus cells of poor responder (n = 28, oocyte count ≤ 4), normo responder (n = 48, 5 ≤ oocyte count ≤ 14), and high responder (n = 26, oocyte count ≥ 15) patient groups continuing IVF treatment. Results: The cumulus cell GST enzyme activity were statistically significantly increased in the high responders group compared to the poor responder and the normo responder's groups (p < 0.001 and p = 0.002, respectively). The cumulus cell MDA levels were significantly decreased in the high responder group compared to the poor responder group (p = 0.008). The cumulus cell CAT (p = 0.175) and ARE (p = 0.124) enzyme activities were examined but no statistically significant difference found between the groups. Conclusion: The significant increase in GST enzyme activity and significant decrease in MDA levels in the high responder group indicate that oxidative stress has an effect oocyte status and quality.

The factors predicting pneumonia in COVID-19 patients: preliminary results from a university hospital in Turkey

Background/aim: Pneumonia is the most serious clinical presentation of COVID-19. This study aimed to determine the demographic, clinical, and laboratory findings that can properly predict COVID-19 pneumonia. Materials and methods: This study was conducted in the Gazi University hospital. All hospitalized patients with confirmed and suspected SARS-CoV-2 infection between 16 March 2020 and 30 April 2020 were analyzed retrospectively. COVID-19 patients were separated into two groups, pneumonia and nonpneumonia, and then compared to determine predicting factors for COVID-19 pneumonia. Variables that had a P-value of less than 0.20 and were not correlated with each other were included in the logistic regression model. Results: Of the 247 patients included in the study 58% were female, and the median age was 40. COVID-19 was confirmed in 70.9% of these patients. Among the confirmed COVID-19 cases, 21.4% had pneumonia. In the multivariate analysis male sex (P = 0.028), hypertension (P = 0.022), and shortness of breath on hospital admission (P = 0.025) were significant factors predicting COVID-19 pneumonia. Conclusion: Shortness of breath, male sex, and hypertension were significant for predicting COVID-19 pneumonia on admission. Patients with these factors should be evaluated more carefully for diagnostic procedures, such as thorax CT.

Ischemic modified albumin as a new biomarker in predicting oxidative stress in alopecia areata

Background/aim: Results show that oxidative stress is a pathophysiologic factor for alopecia areata (AA); however, the markers used can be confounding. Thus, we aimed to investigate the role of oxidative stress in the pathogenesis of AA through an evaluation of ischemia-modified albumin (IMA); other markers of the oxidant/antioxidant system, such as SOD, CAT, GSH-ST, and MDA; and contributing clinical risk factors. Materials and methods: The usefulness of IMA as a new marker for oxidative stress was compared with that of other markers and evaluated in patients with AA. Results: The mean serum level of IMA was of higher statistical significance in AA patients than in the control group (IMA: 0.57 ± 0.01 vs. 0.52 ± 0.02 ΔABSU, P < 0.0001). IMA (P = 0.03, OR = 25.8, 95% CI = 1.4­482.7) was found to be an independent predictor of oxidative stress in patients with AA. Increased severity of AA was found as an independent risk factor for IMA. Conclusion: Long-lasting disease, male sex, >1 site of involvement of disease, and increased severity of disease were correlated with increased oxidation. Presence of AA, male sex, and severe disease were determined to be independent risk factors for antioxidant and oxidant systems. IMA has great potential as a biomarker of oxidative stress in AA when compared to other studied biomarkers.

The effect of levosimendan on lung damage after myocardial ischemia reperfusion in rats in which experimental diabetes was induced.

BACKGROUND: It is known that diabetic complications and lipid peroxidation are closely associated. During ischemia and reperfusion (IR), injury may occur in distant organs, as well as in tissues next to the region exposed to the ischemia, and the lungs can be one of the most affected of these organs. Therefore, this study investigated the effects of levosimendan on lung tissue and the oxidant-antioxidant system in diabetic rats. MATERIALS AND METHODS: The study was conducted in 24 Wistar albino rats that were separated into four groups (C, control; DC, diabetic control; DIR, diabetic IR; and DIRL, diabetic IR levosimendan). Diabetes was induced in 18 rats using streptozotocin (55 mg/kg), and the animals were randomly separated into three groups after the effects of the diabetes became apparent. After a left thoracotomy, ischemia was performed on the myocardial muscle with the left main coronary artery (LAD) for 30 min in the DIR and DIRL groups. After ischemia, the LAD ligation was removed, and reperfusion was applied for 120 min. Single-dose intraperitoneal 12 µg/kg levosimendan was administered to group DIRL before the ischemia. Group DC was evaluated as the diabetic control group, and six rats were considered to be the control group (group C), in which thoracotomy was performed and then closed with no induction of myocardial ischemia. We measured the levels of malondialdehyde, as a lipid peroxidation end product, as well as catalase and glutathione S-transferase activities, as antioxidant enzymes in the lung tissue. Tissue samples were also examined histopathologically. RESULTS: Neutrophil infiltration or aggregation in lung tissue was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.003, P = 0.026, and P = 0.026, respectively). Alveolar wall thickening in lung tissue was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.002, P = 0.002, and P = 0.006, respectively). In addition, the lung tissue damage score was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.001, P = 0.004, and P = 0.007, respectively). Finally, catalase and glutathione S-transferase activity levels were significantly higher in the DIR group compared with those observed in the C, DC, and DIRL groups. CONCLUSIONS: Although diabetes increases lipid peroxidation, it suppresses antioxidant activity. Our results showed that levosimendan had a protective effect against lung damage secondary to IR in the rats with induced diabetes. We recommend that experimental and clinical studies be conducted to examine the effects of levosimendan at different doses and different IR durations on various organs for clinical use.

The effects of iloprost on ischemia-reperfusion injury in skeletal muscles in a rodent model.

PURPOSE: The aim of this study was to investigate the effects of iloprost (IL) on ischemia-reperfusion injury in a rodent model. MATERIALS AND METHODS: Twenty-four Wistar Albino rats were randomized into four groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Only laparotomy was applied in group S (Sham). Ischemia-reperfusion group (group I/R) underwent ischemia and reperfusion performed by clamping and declamping of the infrarenal abdominal aorta for 120 min. The iloprost group (group IL) received intravenous infusion of IL 0.5 ng/kg/min, without I/R. Group I/R + IL received intravenous infusion of IL 0.5 ng/kg/min immediately after 2 h period of ischemia. At the end of the reperfusion period, all rats were killed under anesthesia and skeletal muscle samples of lower extremity were harvested for biochemical and histopathologic analyses. RESULTS: Tissue levels of endothelial nitric oxide were significantly higher in I/R groups than those in groups S and IL. The heat shock protein 60 levels were higher in group I/R than the other groups. But the heat shock protein 60 levels in group I/R + IL were found to be similar with the groups S and IL. Malondialdehyde levels were significantly higher in group I/R. On the other hand, in group I/R + IL, malondialdehyde levels were higher than those in groups S and IL but lower than those in group I/R. Superoxide dismutase (SOD) enzyme activities were found to be significantly lower in group I/R than the other groups. Also in group I/R/I, the SOD enzyme activities were higher than those in group I/R. But, in group I/R + IL, SOD levels were found to be higher than those in group I/R but lower than those in groups S and IL. CONCLUSIONS: These results indicate that IL has protective effects on I/R injury in skeletal muscle in a rodent model.

Effect of fullerenol C60 on lung and renal tissue in lower extremity ischemia­reperfusion injury in sevoflurane­treated rats.

The aim of the present study was to examine the effect of fullerenol C60 on lung and kidney tissue in sevoflurane­treated rats with lower extremity ischemia­reperfusion (IR) injury. A total of 30 Wistar albino rats weighing 225­275 g were used and were equally divided into five groups (n=6/group): i) Sham; ii) IR; iii) IR­fullerenol C60 (IR­FUL); iv) IR­sevoflurane; and v) IR­fullerenol C60­sevoflurane (IR­FUL­SEVO). Fullerenol C60 was administered intraperitoneally prior to lower extremity IR induction and sevoflurane was administered during the IR injury. Subsequently, lung and kidney histopathological examinations, and serum biochemical analyses were performed. Lung tissue showed markedly increased congestion and neutrophil infiltration in the IR group compared with in the sham group, and notable decreases in congestion and neutrophil infiltration were observed in the treatment groups compared with in the IR group. In the histopathological evaluation of the kidney samples, vacuolization, loss of brush border in tubular epithelial cells, tubular epithelial loss and varying degrees of tubular damage were observed in all groups that underwent IR. There was a significant increase in the mean renal tubule injury score in all IR groups compared with that in the sham group. In addition, the mean kidney injury score was significantly lower in the IR­FUL and IR­FUL­SEVO groups than that in the IR group. It was observed that the expression levels of tumor necrosis factor­α, interleukin 1ß and intercellular adhesion molecule 1 in the lung and kidney tissues were increased following IR, and were decreased in the groups treated with fullerenol C60 and sevoflurane. Notably, it was determined that the reduction in cytokine expression was greatest in the IR­FUL group. When the oxidant status parameters in the lungs and kidneys were examined, thiobarbituric acid reactive substances levels, and catalase and glutathione S­transferase enzyme activities were significantly different in the groups receiving sevoflurane or fullerenol C60 treatment compared with those in the IR group. The present study demonstrated the protective effects of fullerenol C60 on the lung and kidney tissues of rats under sevoflurane anesthesia after establishment of lower extremity IR. The results of the present study showed that fullerenol C60 can reduce oxidative and histopathological damage in the lungs and kidneys following IR of the lower extremities.

Effects of sevoflurane and fullerenol C60 on lower limb ischemia-reperfusion injury in streptozocin-induced diabetic mice.

BACKGROUND: Ischemia-reperfusion injury (IRI) poses a significant challenge for physicians, necessitating the management of cell damage and the preservation of organ functions. Various surgical procedures, such as vascular surgery on extremities, temporary cross-clamping of the abdominal aorta in aortic surgery, and the use of a tourniquet in extremity surgeries, may induce lower limb IRI. The susceptibility to IRI is heightened in individuals with diabetes. This study aimed to investigate the effects of fullerenol C60 and sevoflurane on mouse muscle tissue in a lower limb IRI model and to assess their potential in preventing complications arising from ischemia-reperfusion in mice with streptozocin-induced diabetes. METHODS: A total of 36 adult Swiss albino mice were randomly divided into six groups, each consisting of six mice: control group (group C), diabetes group (group D), diabetes-ischemia/reperfusion group (group DIR), diabetes-ischemia/reperfusion-fullerenol C60 group (group DIR-FC60), diabetes-ischemia/reperfusion-sevoflurane group (group DIR-S), and diabetes-ischemia/reperfusion-sevoflurane-fullerenol C60 group (DIR-S-FC60). Streptozocin (55 mg/kg) was intraperitoneally administered to induce diabetes in the relevant groups, with mice displaying blood glucose levels of 250 mg/dL or higher at 72 h were considered diabetic. After 4 weeks, all groups underwent laparotomy under anesthesia. In DIR-FC60 and DIR-S-FC60 groups, fullerenol C60 (100 mg/kg) was intraperitoneally administrated 30 min before the ischemia period. Sevoflurane, delivered in 100% oxygen at a rate of 2.3% and 4 L/min, was administered during the ischemia period in DIR-S and DIR-S-FC60 groups. In the IR groups, a microvascular clamp was placed on the infrarenal abdominal aorta for 120 min during the ischemia period, followed by the removal of the clamp and a 120-min reperfusion period. At the end of the reperfusion, gastrocnemius muscle tissues were removed for histopathological and biochemical parameter examinations. RESULTS: Histopathological examination revealed a significant reduction in the disorganization and degeneration of muscle cells in the DIR-S-FC60 group compared to the DIR group (p = 0.041). Inflammatory cell infiltration was notably lower in the DIR-S, DIR-FC60, and DIR-S-FC60 groups than in the DIR group (p = 0.031, p = 0.011, and p = 0.013, respectively). The total damage scores in the DIR-FC60 and DIR-S-FC60 groups were significantly lower than in the DIR group (p = 0.018 and p = 0.008, respectively). Furthermore, the levels of malondialdehyde (MDA) in the DIR-S, DIR-FC60, and DIR-S-FC60 groups were significantly lower than in the DIR group (p < 0.001, p < 0.001, and p < 0.001, respectively). Catalase (CAT) enzyme activity in the DIR-S, DIR-FC60, and DIR-S-FC60 groups was higher than in the DIR group (p = 0.001, p = 0.014, and p < 0.001, respectively). Superoxide dismutase (SOD) enzyme activity in the DIR-FC60 and DIR-S-FC60 groups was also higher than in the DIR group (p < 0.001 and p = 0.001, respectively). CONCLUSION: Our findings indicate that administering fullerenol C60 30 min prior to ischemia in diabetic mice, in combination with sevoflurane, led to a reduction in oxidative stress and the correction of IR-related damage in muscle tissue histopathology. We believe that the administration of fullerenol C60 before IR, coupled with sevoflurane administration during IR, exerts a protective effect in mice.

Dexmedetomidine's Effects on the Livers and Kidneys of Rats with Pancreatic Ischemia-Reperfusion Injury.

Objective: 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.

Protective effects of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in bladder ischemia-reperfusion injury in rats.

The aim of the present study was to evaluate the protective effects of the NF-кB inhibition with pyrrolidine-dithiocarbamate (PDTC) in ischemia-reperfusion (I/R) injury in the rat bladder. Twenty-four Sprague-Dawley male rats were divided into three groups. Group I; (n = 8) control, group II; (n = 8) I/R group; group III (n = 8) I/R and PDTC treatment. Superoxide dismutase (SOD), catalase (CAT), and gluatathione-S-transferase (GST) enzymes was studied in bladder tissue. Lipid peroxidation (as TBARS) levels in tissue homogenate were measured with thiobarbituric acid reaction. All the slides were stained with NF-кB, p53 and HSP60 immunohistochemistry for detection genome destruction and tissue stress, respectively. Our results show that the mean TBARS levels were significantly higher in group II (p < 0.05). The TBARS levels were significantly decreased in group III compared with the group II (p < 0.05). CAT, SOD and GST activities were decreased in group II, but these enzymes levels were significantly increased in group III according to the group II (p < 0.05). Under microscopic evaluation NF-кB expression increased significantly in group II compared to the group I (p < 0.05) and then decreased in group III (p < 0.05). HSP60 and p53 expression in group II was increased significantly compared with group I. Under microscopic evaluation we detected that HSP60 and p53 expression was increased significantly in group II compared with group I. In group III PDTC administration was decreased the HSP60 and p53 expression, this difference was statistically significant (p < 0.05). The results of the present study have demonstrated that NF-кB inhibition with PDTC protects and provides beneficial effects on ischemia/reperfusion stress related bladder tissue destruction.

Synthesis and pharmacological evaluation of some novel thebaine derivatives: N-(tetrazol-1H-5-yl)-6,14-endoethenotetrahydrothebaine incorporating the 1,3,4-oxadiazole or the 1,3,4-thiadiazole moiety.

In this study, we synthesized some novel N-(tetrazol-1H-5-yl)-6,14-endoethenotetrahydrothebaine 7α-substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives as potential analgesic agents. The structures of the compounds were established on the basis of their IR, ¹H NMR, ¹³C NMR, 2D NMR, and high-resolution mass spectral data. The analgesic activity was evaluated by a rat-hot plate test model and a rat tail-flick model. Compound 12 showed analgesic activity higher than that of morphine. In addition to a histopathological and biochemical evaluation, the LD50 dose for the most active compound 12 was determined.

Protective effect of cerium oxide on testicular function and oxidative stress after torsion/detorsion in adult male rats.

Testicular torsion (T)/detorsion (D) can cause testicular injury due to the rotation of the spermatic cord and its vessels, therefore it represents an urological emergency that is surgically treated. Oxidative damage occurs in the testis and distant organs because of the overproduction of free radicals and overexpression of proinflammatory cytokines by reperfusion after surgery. Cerium oxide (CeO2) nanoparticles, a material also known as nanoceria, have regenerative antioxidant properties on oxidative stress. The present study aimed to investigate the effects of nanoceria on testis tissues in testicular T/D in rats. A total of 24 rats were equally and randomly divided into four groups: Control, CeO2, T/D and CeO2-T/D groups. Left inguinoscrotal incision was performed in the control group. In the CeO2 group, 0.5 mg/kg CeO2 was given intraperitoneally 30 min before inguinoscrotal incision. In the T/D group, unilateral testicular T/D was performed through an inguinoscrotal incision and rotating the left testis 720˚ clockwise, which was then left ischemic for 120 min, followed by 120 min of reperfusion. In the CeO2-T/D group, 0.5 mg/kg CeO2 was given intraperitoneally 30 min before testicular T/D. At the end of the experiment, testis tissues were removed for histopathological and biochemical examinations. The samples were histologically examined, Glutathione-s transferase (GST), catalase (CAT), paraoxonase (PON) activities and malondialdehyde (MDA) levels were measured via biochemical analysis methods, while the expression levels of p53, Bax and Bcl-2 were detected using immunohistochemistry. The present results revealed statistically significant inter-group differences in PON, CAT and GST activities and MDA levels. GST, CAT and PON activities were significantly higher, whereas MDA levels in the CeO2-T/D group were significantly lower compared with those in the T/D group. The T/D group had increased Bax and decreased Bcl-2 expression levels in their seminiferous tubules compared with the control and CeO2 groups. CeO2 treatment led to downregulation of Bax and upregulation of Bcl-2. The expression of p53 was high in the T/D group compared with that in the control and CeO2 groups, and was upregulated in all germinal cells. However, compared with that in the T/D group, p53 expression was significantly decreased in the CeO2-T/D group. The testicular injury score significantly increased in the CeO2-T/D group compared with the control and CeO2 groups. Rats in the CeO2-T/D group demonstrated significantly milder tissue lesions compared with those in T/D group. The present findings indicated that nanoceria may protect testis in rats against the harmful effects of T/D. Further studies are required to evaluate how CeO2 reduces oxidative stress and cell death in testis tissue that underwent T/D-related injury.

Artemisinin reduces acute ovarian ischemia-reperfusion injury in rats.

Artemisinin (ARS) is well known as an effective agent in the treatment of malaria through the rapid elimination of Plasmodium falciparum parasites. This study aims to investigate the effect of ARS in treating adnexal torsion, one of the most common gynecological surgical emergencies. ARS was administered intraperitoneally once 30 min before unilateral ovarian torsion in two different doses (10 mg/kg vs. 50 mg/kg). Torsion was maintained for 3 h and then held in the detorted state for 3 h. Bilateral adnexectomy was performed to measure antioxidant enzyme activities and oxidant levels on the ipsilateral ovary and to make histopathological and immunohistochemical analyses on the contralateral ovary. Ischemia-reperfusion (I/R) injury dramatically upregulated the activities of CAT, GST, and MDA levels in the ipsilateral ovary, which were all downregulated by ARS treatment. A significant increase in follicular cell degeneration, congestion, and edema in the contralateral ovary was seen in the I/R group, which was significantly reduced with ARS treatment. Furthermore, I/R injury resulted in a significant increase in apoptosis as shown by the increased levels of BAX and CASP-3, and decreased levels of BCL-2 whereas ARS significantly reduced the impact of the injury. Our data, based on a rat I/R injury model, show that both ipsilateral and contralateral ovaries are protected with ARS pretreatment, and 50 mg/kg ARS treatment demonstrates to be more effective than the 10 mg/kg ARS.

Effects of cerium oxide on liver tissue in liver ischemia­reperfusion injury in rats undergoing sevoflurane anesthesia.

During liver surgery and transplantation, periods of partial or total vascular occlusion are inevitable and result in ischemia-reperfusion (IR) injury. Nanomedicine uses the latest technological advancement, which has emerged from interdisciplinary efforts involving biomedical sciences, physics and engineering to protect and improve human health. Antioxidant nanoparticles are potential therapeutic agents. The present study investigated the effects of cerium oxide (Co) administration and sevoflurane anesthesia on liver tissue with IR injury. A total of 36 rats were randomly divided into control, Co, IR, IR-Sevoflurane (IRS), Co + IR and Co + IRS groups. In the IR, IRS and Co + IRS groups, hepatic IR was induced. Intraperitoneal Co was administered to the Co groups 30 min before ischemia. Sevoflurane was administered to the IRS and Co + IRS groups during IR injury. Liver tissue samples were examined under the light microscope by staining with hematoxylin and eosin. Thiobarbituric acid (TBARS) levels as well as catalase (CAT) and glutathione-S-transferase (GST) enzyme activity were evaluated in liver tissue samples. The IR group had considerably more hydropic degeneration, sinusoidal dilatation and parenchymal neutrophil infiltration than the Co, IRS, Co + IR and Co + IRS groups. CAT and GST enzyme activity were significantly higher in Co and Co + IR groups compared with the IR group. TBARS levels were significantly lower in Co, IRS, Co + IR and Co + IRS groups compared whit those in the IR group. Intraperitoneal injection of Co with sevoflurane decreased oxidative stress and damage to the liver.

Effects of fullerene C60 on liver tissue in liver ischemia reperfusion injury in rats undergoing sevoflurane anesthesia.

This study aimed to investigate the effects of fullerene C60 on rat liver tissue in a liver ischemia reperfusion injury (IRI) model under sevoflurane anesthesia to evaluate the ability of nanoparticles to prevent hepatic complications. A total of 36 adult female Wistar Albino rats were divided into six groups, each containing six groups as follows: sham group (Group S), fullerene C60 group (Group FC60), ischemia-reperfusion group (Group IR), ischemia-reperfusion-sevoflurane group (Group IR-Sevo), ischemia-reperfusion-fullerene C60 group (Group IR-FC60), and ischemia-reperfusion-fullerene C60-sevoflurane group (Group IR-FC60-Sevo). Fullerene C60 100 mg/kg was administered to IR-FC60 and IR-FC60-Sevo groups. In the IR group, 2 h of ischemia and 2 h of reperfusion were performed. At the end of reperfusion, liver tissues were removed for biochemical assays and histopathological examinations. Hepatocyte degeneration, sinusoidal dilatation, prenecrotic cells, and mononuclear cell infiltration in the parenchyma were significantly higher in Group IR than in all other groups. Thiobarbituric acid reactive substances levels were significantly higher in Group IR than in the other groups, and the lowest thiobarbituric acid reactive substances level was in Group IR-FC60 than in the other groups, except for Groups S and FC60. Catalase and Glutathione-S-transferase activities were reduced in the IR group compared to all other groups. Fullerene C60 had protective effects against liver IR injury in rats under sevoflurane anesthesia. The use of fullerene C60 could reduce the adverse effects of IRI and the associated costs of liver transplantation surgery.

The Effect of Sevoflurane and Fullerenol C 60 on the Liver and Kidney in Lower Extremity Ischemia-Reperfusion Injury in Mice with Streptozocin-Induced Diabetes.

Objective: This study aimed to demonstrate whether fullerenol C60, sevoflurane anesthesia, or a combination of both had protective effects on the liver and kidneys in lower extremity ischemia-reperfusion injury (IRI) in mice with streptozocin-induced diabetes. Methods: A total of 46 Swiss albino mice were divided into six groups as follows: control group (group C, n=7), diabetes group (group D, n=7), diabetes-ischemia/reperfusion (group DIR, n=8), diabetes-ischemia/reperfusion-fullerenol C60 (group DIR-FC60, n=8), diabetes-ischemia/reperfusion-sevoflurane (group DIR-S, n=8), and the diabetes-ischemia/reperfusion-fullerenol C60-sevoflurane (group DIR-S-FC60, n=8). Fullerenol C60 (100mg/kg) was administered intraperitoneally 30 min before the ischemia-reperfusion procedure to the fullerenol groups (DIR-FC60 and DIR-S-FC60). In the DIR groups, 2 hours (h) ischemia-2h reperfusion periods were performed. In the sevoflurane groups, sevoflurane was applied during the ischemia-reperfusion period with 100% O2. Liver and kidney tissues were removed at the end of the reperfusion procedure for biochemical and histopathological examinations. Results: In liver tissue, hydropic degeneration, sinusoidal dilatation, pycnotic nuclei, prenecrotic cells, and mononuclear cell infiltration in parenchyma were significantly more frequent in group DIR than in groups D and group C. In terms of the histopathologic criteria examined, more positive results were seen in group DIR-FC60, and when group DIR-FC60 was compared with group DIR, the difference was significant. The best results in AST, ALT, glucose, TBARS levels, and SOD enzyme activities in liver tissue were in group DIR-FC60 compared with group DIR, followed by groups DIR-S-FC60 and DIR-S, respectively. Regarding TBARS levels and SOD enzyme activities in kidney tissue, the best results were in groups DIR-FC60, DIR-S-FC60, and DIR-S, respectively. Conclusion: According to our findings, it is clear that fullerenol C60 administered intraperitoneally 30 min before ischemia, alone or together with sevoflurane, reduces oxidative stress in distant organ damage caused by lower extremity IRI, and reduces liver and kidney tissue damage in histopathologic examinations.

The role of pomegranate seed oil on kidney and lung tissues in the treatment of sepsis: animal pre-clinical research.

OBJECTIVES: Sepsis is a common disease with a high mortality. Decreasing the speed is possible with early and intensive therapy. However, most medicines have been tested, but none has proven effective. Therefore, the study aimed to discover the protective and therapeutic effects of pomegranate seed oil (PSO). METHODS: The cecal ligation puncture (CLP) method was used to induce sepsis. The experimental procedure was started with the animals divided haphazardly into four groups: control (C), sepsis (CLP), CLP + low dose PSO (CLP + LD), and CLP + high dose PSO (CLP + HD). First, the cecum was filled with feces. The full cecum was tied under the ileocecal valve for ligation and punctured. At 1 hour after CLP, 0.32 mg/kg and 0.64 mg/kg of PSO were administered. 24 hours after, lung and kidney specimens were collected. RESULTS: Neutrophil infiltration/aggregation and alveolar wall thickness decreased in lung with PSO groups compared with the CLP. The findings for overall lung injury were similar. In renal, all parameters were increased in the CLP compared with C, except for vascular vacuolization and hypertrophy. According to the CLP, all parameters were significantly lower in CLP + HD. Furthermore, glomerular vacuolization, degeneration, and necrosis of tubular cell, dilatation of bowman space, and tubular hyaline cylinders reduced CLP + LD versus CLP. Thiobarbituric acid-reactive substances decreased in lung, with the PSO groups. In addition, superoxide dismutase increased in PSO groups versus CLP. CONCLUSIONS: We conclude that the high-dose PSO is especially effective in treating sepsis.