Efficacy of ABCA1 Transporter Proteins in Patients with Endometrial Cancer: an In Vitro Study.

Objectives: Endometrial carcinoma (EC) is a typical gynecological malignant tumor that occurs more frequently every year. Obesity is a significant contributor to the development of EC and its prognosis. Lipid metabolism and malignant tumors have a long history of association. Elevated cholesterol levels are made possible by adenosine triphosphate-binding cassette protein A1 (ABCA1) deficiency, which eventually promotes cancer cell survival. The aim of this study was to examine at the ABCA1 gene expression levels in EC patients. The relationship between ABCA1 and the occurrence, progression, and prognosis of EC is discussed in this article as a potential mechanism. Materials and Methods: The samples of 45 endometrial adenocarcinoma patients were retrospectively included in this study and they were further divided into Grade 1 (15), Grade 2 (15), Grade 3 (15) tumors, control group. Twenty-nine endometrial tissues without a confirmed diagnosis of endometrial cancer made up the control group. ABCA1 gene expression was examined using real-time polymerase chain reaction. Results: According to the results, the gene expressions of the patient group were higher than the control group When each Grade was compared with the control group, statistically significant results were obtained. After analyzing the data, it was found that the patient group was generally higher than the control group (p < 0.05) and there were differences in the grades of the patient group (p < 0.05). When the ABCA1 expressions of the grade groups and control groups were compared separately, a difference was found between Grade 1, Grade 2 and Grade 3 and the control group (p= 0.0001). Conclusion: According to the findings of our study, a key component in the growth of EC tumors is the increase in cholesterol production caused by a reduction in ABCA1.

Role of acetyl-CoA acetyltransferase 1 expression in the molecular mechanism of adenomyosis.

Objective: Adenomyosis is a benign uterine illness characterized by endometrial gland and stromal invasion into the myometrium. Acetyl-CoA acetyltransferase 1 (ACAT1) is an enzyme localized in mitochondria that is involved in ketogenesis and ketolysis processes by reversibly catalyzing the formation of acetoacetyl-CoA from two acetyl-CoA molecules. The current study investigated the expression of the ACAT1 molecule in tissue samples of patients diagnosed with adenomyosis and healthy endometrial tissues. It is aimed to determine the differences in ACAT1 gene expression and in this way to discover the first information about the role of ACAT1 in the development and molecular mechanism of adenomyosis. Materials and Methods: In the current retrospective study, formalin-fixed paraffin-embedded archival tissues were employed. A total of 76 patient samples were included in the study. Of these samples, 28 are adenomyotic tissue (Group I), 30 are eutopic endometrial tissue (Group II), and 18 are the Control Group. In these groups, the expression levels of the ACAT1 gene were determined by the reverse transcription-polymerase chain reaction method. Results: When the expression results of the ACAT1 gene were evaluated, statistically significant differences were found between the groups (p<0.05). There was a difference between Group I-Group II and Group I-Control Group regarding the ACAT1 gene. No statistically significant change was observed between Group II and Control Group. It is a remarkable finding that the expression of ACAT1 in adenomyosis tissue is decreased compared with both eutopic endometrium and control groups tissues. Conclusion: The results suggest that ACAT1 may be associated with the molecular pathogenesis of adenomyosis.

Altered VEGF, Bcl-2 and IDH1 expression in patients with adenomyosis.

PURPOSE: Adenomyosis is a benign uterine disease resulting from the myometrial invasion of the endometrial gland and stroma. In the current study, angiogenesis, apoptosis and energy metabolism were investigated in adenomyosis. METHODS: A retrospective study was performed using paraffin archival tissues. Three groups were included in the study: Group I and Group II; ectopic and eutopic endometrial tissues of patients with adenomyosis, respectively, and Control Group; endometrial tissue of individuals without adenomyosis. Vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), intercellular adhesion molecule 1 (ICAM-1) and hypoxia-inducible factor 1 alpha (HIF-1A) levels were evaluated as angiogenic markers. Bcl-2, caspase-9 and caspase-3 levels were investigated as apoptotic indicators, and isocitrate dehydrogenase 1 (IDH1), succinate dehydrogenase complex subunit C (SDHC) and fumarate hydratase (FH) levels were also examined as energy metabolism markers. Gene expression levels of all parameters were determined by RT-PCR. RESULT: VEGF expression levels were found to be increased in Group I according to the control group and Group II. Bcl-2 expression levels were found to be increased in the Group I compared to the Group II. It was determined that expression levels of IDH1 were decreased in the Group I and Group II compared to the Control Group. There was no significant difference in the other examined parameters. Although we did not find a significant difference in HIF-1A levels between the groups, we found a positive correlation between VEGF and HIF-1A in the Group I. CONCLUSION: These results point out that VEGF, HIF-1A, Bcl-2 and IDH1 may be associated with the etiology of adenomyosis.

Potential renoprotective effects of silymarin against vancomycin-induced nephrotoxicity in rats.

Silymarin (SLY), a flavonoid complex isolated from the seeds of Silybum marianum (Asteraceae), has antioxidant, anti-apoptotic, anti-inflammatory, and anti-lipid peroxidative effects. Vancomycin (VA), used for treating serious infections, has been associated with nephrotoxicity, which limits its use. Therefore, this study aimed to investigate the potential renoprotective effects of SLY on VA-induced nephrotoxicity using renal, apoptotic (caspase-3, caspase-8, and caspase-9 enzyme activities), and oxidative stress [nitric oxide (NO) and malondialdehyde (MDA)] markers; serum blood urea nitrogen (BUN) and creatinine levels; and histopathological examination. A total of 49 male Wistar albino rats were used (n = 7): control [saline, intraperitoneally (i.p.)], dimethyl sulfoxide (i.p.), VA [400 mg/(kg-day), i.p.], SLY100 [100 mg/(kg-day), i.p.], VA + SLY50 [50 mg/(kg-day), i.p.], VA + SLY100 [100 mg/(kg-day), i.p.], and VA + SLY200 [200 mg/(kg-day), i.p.]. SLY was administered once daily for 8 days. One day after the first treatment of SLY, VA administration was started and continued for 7 days. The levels of serum creatinine and BUN were evaluated using ELISA, caspase enzyme activities and levels of MDA and NO in the kidney tissues were evaluated by the colorimetric methods. The serum BUN, creatinine, NO, MDA levels, and caspase activities were significantly higher in VA group than in control (p < 0.05). However, caspase activities were significantly lower in VA + SLY200 than in VA (p < 0.05). The MDA, serum BUN, and creatinine levels were significantly lower in VA + SLY (50, 100, and 200) groups than in VA group (p < 0.05). VA + SLY200 was found to be the most effective group based on the caspase activities; MDA, NO, serum BUN, creatinine levels; and histopathological findings.

Potential protective effects of naringenin against vancomycin-induced nephrotoxicity via reduction on apoptotic and oxidative stress markers in rats.

Vancomycin (VCM), a glycopeptide antibiotic, is a drug widely used in severe infections. However, VCM induce notable nephrotoxic side effects. Naringenin (NAR) is a natural of flavonoid and are known as strongly antioxidant, nefroprotective, antiapoptotic, and anti-inflammatory. The purpose of this study was to determine the potential protective effects of NAR against VCM-induced nephrotoxicity by measuring apoptotic and oxidative stress markers and evaluating histopathological alterations in rats. For this purpose, we used male Wistar albino rats that divided into seven groups: (i) Control [saline, intraperitoneally (i.p.)], (ii) carboxymethyl cellulose (0.5% CMC, orally), (iii) VCM (400 mg/kg, i.p.), (iv) NAR100 (100 mg/kg, orally), (v) VCM + NAR25 (25 mg/kg, orally), (vi) VCM + NAR50 (50 mg/kg, orally), and (vii) VCM + NAR100 (100 mg/kg, orally) groups. VCM administration was started one day after the first treatment of NAR and continued across 7-day. Caspase-3, -8, and-9 activities and malondialdehyde (MDA) and nitric oxide (NO) levels were measured by colorimetric methods in the kidney tissues, creatinine, and blood urea nitrogen (BUN) levels were analyzed based on ELISA in serum. Caspase-3 and -8 activities, NO levels, serum creatinine and BUN levels were significantly higher in VCM group in comparison with VCM + NAR (25, 50, and 100) groups (p < 0.05). Caspase-9 activity and MDA were significantly higher in VCM group compared to VCM + NAR (25 and 50) groups (p < 0.05). Histopathological alterations in VCM group were significantly diminished by administration of NAR, especially NAR 25. In conclusion, NAR 25 and 50 mg have more potent protective effects on VCM-induced nephrotoxicity compared to NAR 100 mg.

Tumor necrosis factor-superfamily 15 gene expression in patients with sickle cell disease.

OBJECTIVE: The aim of this study was to investigate the relation between tumor necrosis factor-superfamily 15 (TNFSF15) gene expression and clinical findings in children with sickle cell disease (SCD). MATERIALS AND METHODS: Forty-nine patients with SCD and 38 healthy controls were included in this study. TNFSF15 gene expression and plasma levels were analyzed. TNFSF15 gene expression was compared in subgroups considering the frequency of painful crises and acute chest syndrome (ACS). RESULTS: It was found that TNFSF15 gene expression was significantly higher in patients with SCD than the controls (p=0.001), whereas there was no significant difference between the patients with SCD and the control groups considering plasma levels of TNFSF15. TNFSF15 gene expression was also significantly higher in SCD patients with ACS (p=0.008). CONCLUSION: These findings suggest that TNFSF15 may have a role in the pathogenesis of SCD presenting with ACS. Further studies on larger groups are needed to determine the function of TNFSF15 in SCD patients with ACS and pulmonary hypertension. Analysis of TNFSF15 expression may also serve as a promising approach in ACS therapy.

Role of ACE I/D gene polymorphisms on the effect of ramipril in inflammatory response and myocardial injury in patients undergoing coronary artery bypass grafts.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors block angiotensin II formation and release bradykinin, which is effective in the regulation of oxidoinflammatory injury. Some reports denote alterations in the effectiveness of ACE inhibitors in association with ACE insertion/deletion (I/D) gene polymorphisms. This study investigates the effects of ramipril on the oxidoinflammatory cytokines (IL-6, IL-8, TNF-alpha) and TnT (myocardial injury marker) and their alteration in association with ACE I/D gene polymorphisms. METHODS: The study group (n = 51) patients received ramipril before coronary artery bypass grafting (CABG), while patients not receiving ramipril (n = 51) constituted the controls. TNFα, IL-6, and IL-8 were evaluated using ELISA and TnT by electrochemiluminescence methods before the induction of anesthesia (t1), at the 20th minute following cross-clamping (t2), at the end of the operation (t3), and at the 24th hour from the commencement of anesthesia (t4). Genotyping was performed by PCR. RESULTS: Differences between the groups were significant at t4 for the TNFα and at t3 for IL-6 (p < 0.05). The TnT levels increased from t2 onward in the control group and were highest in t3. Changes in t3 and t4 values in both groups according to their t1 values were significant (p < 0.05). However, differences between the groups were insignificant (p > 0.05). The IL-6, IL-8, TNFα, and TnT serum levels had no correlation with the ACE I/D gene polymorphism. CONCLUSION: Low cytokine and TnT levels in the study group, especially after cross-clamping, may indicate the protective effect of ramipril from oxidoinflammatory injury. This effect did not appear to be associated with the ACE I/D gene polymorphism.

Intravitreal bevacizumab effects on VEGF levels in distant organs: an experimental study.

PURPOSE: The aim of this study was to determine the effects of single-dose intravitreal bevacizumab on the levels of vascular endothelial growth factor (VEGF) in serum and distant organs. METHODS: Adult New Zealand albino rabbits (n = 40) were divided into experimental and control groups. Experimental rabbits received a single 0.05 ml intravitreal injection of 1.25 mg bevacizumab (Avastin) into the right eye, and control rabbits (n = 8) received no injection. Following injection, group 1 rabbits (n = 8) were sacrificed on day 1, group 2 rabbits (n = 8) on day 7, group 3 rabbits (n = 8) on day 14, and group 4 rabbits (n = 8) on day 28; control rabbits were sacrificed on day 28. After sacrifice, samples of brain, heart, liver, kidney and blood were collected. Levels of VEGF in serum and tissue were measured using enzyme-linked immunosorbent assay. The presence of bevacizumab was evaluated by immunofluorescence staining in tissues. RESULTS: Positive bevacizumab immunoreactivity was observed in brain, heart and kidney. Serum VEGF levels significantly decreased in groups 3 and 4 compared with controls (p < 0.05). Liver VEGF levels significantly decreased in group 3 compared with controls (p < 0.05). CONCLUSIONS: Intravitreal bevacizumab not only may escape from the blood-retinal barrier and enter the general circulation, but also may be disseminated to distant organs. Our study demonstrates that a single dose of intravitreally injected bevacizumab decreases VEGF levels in serum and liver.

Contribution of RhoA/Rho-kinase/MEK1/ERK1/2/iNOS pathway to ischemia/reperfusion-induced oxidative/nitrosative stress and inflammation leading to distant and target organ injury in rats.

The small G protein RhoA and its downstream effector Rho-kinase play an important role in various physiopathological processes including ischemia/reperfusion (I/R) injury. Reactive oxygen and nitrogen species produced by iNOS and NADPH oxidase are important mediators of inflammation and organ injury following an initial localized I/R event. The aim of this study was to determine whether RhoA/Rho-kinase signaling pathway increases the expression and activity of MEK1, ERK1/2, iNOS, gp91(phox), and p47(phox), and peroxynitrite formation which result in oxidative/nitrosative stress and inflammation leading to hindlimb I/R-induced injury in kidney as a distant organ and gastrocnemius muscle as a target organ. I/R-induced distant and target organ injury was performed by using the rat hindlimb tourniquet model. I/R caused an increase in the expression and/or activity of RhoA, MEK1, ERK1/2, iNOS, gp91(phox), p47(phox), and 3-nitrotyrosine and nitrotyrosine levels in the tissues. Although Rho-kinase activity was increased by I/R in the kidney, its activity was decreased in the muscle. Serum and tissue MDA levels and MPO activity were increased following I/R. I/R also caused an increase in SOD and catalase activities associated with decreased GSH levels in the tissues. Y-27632, a selective Rho-kinase inhibitor, (100µg/kg, i.p.; 1h before reperfusion) prevented the I/R-induced changes except Rho-kinase activity in the muscle. These results suggest that activation of RhoA/Rho-kinase/MEK1/ERK1/2/iNOS pathway associated with oxidative/nitrosative stress and inflammation contributes to hindlimb I/R-induced distant organ injury in rats. It also seems that hindlimb I/R induces target organ injury via upregulation of RhoA/MEK1/ERK1/2/iNOS pathway associated with decreased Rho-kinase activity.

Apoptotic and anti-angiogenic effects of benzimidazole compounds: relationship with oxidative stress mediated ischemia/reperfusion injury in rat hind limb.

Ischemia/reperfusion (I/R)-induced injury is a pathophysiological process consisting of a complex cascade characterized by an increase in reactive oxygen species production, pro-inflammatory cytokine release, and activated endothelial cells leading to cell damage and death. The aim of this study was to investigate effects of substituted 2-benzylbenzimidazole derivatives, 2-(3-methoxybenzyl)benzimidazole (BB3) and 2-(4-methoxybenzyl)benzimidazole (BB4), on I/R-induced changes in the markers of oxidative stress, apoptosis, and angiogenesis in rats. BB3 and BB4 were synthesized with microwave irradiation and conventional Phillips methods. I/R was performed by occlusion of femoral artery. Catalase activity and reduced glutathione (GSH) levels as well as caspase-3, -8, and -9 activities were measured in muscle tissues as an index for oxidative stress and apoptosis, respectively. Vascular endothelial growth factor (VEGF) levels as an index for angiogenesis were also measured in the muscle tissues and sera. I/R decreased GSH levels, increased catalase activity and VEGF levels, and did not change caspase-3, -8, and -9 activities compared to control groups. BB3 and BB4 caused a further decrease in GSH levels and increased caspase-3, -8, and -9 activities in I/R group. These compounds caused a further increase in catalase activity and prevented the increase in VEGF levels induced by I/R. These data suggest that BB3 and BB4 exhibit apoptotic and anti-angiogenic activity with pro-oxidative effects resulting in oxidative stress in pathophysiological process of I/R-induced hind limb injury in rats.

Increased production of nitric oxide mediates selective organ-specific effects of endotoxin on oxidative stress.

Endotoxemic shock is a systemic inflammatory response that is associated with increased nitric oxide (NO) production by inducible NO synthase (iNOS) which contributes to hypotension, vascular hyporeactivity, and multiple organ failure. Oxidative stress (OS) is a major contributing factor to high morbidity and mortality in endotoxemic shock. We have previously demonstrated that endotoxin-induced fall in blood pressure is associated with an increase in nitrite levels in serum, kidney, heart, thoracic aorta (TA), and superior mesenteric artery (SMA), a decrease in malondialdehyde (MDA) levels in the kidney, heart, TA, and SMA, and an increase in myeloperoxidase (MPO) activity in the heart and TA, but a decrease in the kidney and SMA of rats. In this study, we further investigated whether increased production of iNOS-derived NO contributes to endotoxin induced changes in the biomarkers of OS in the liver, lungs, brain, spleen, and femoral artery (FA) of rats. Endotoxin-induced increase in nitrite production was associated with a decrease in reduced glutathione levels in the liver, lungs, brain, spleen, and FA. MPO activity was increased by endotoxin in the lungs, spleen, and FA, but decreased in the liver and brain. MDA levels were increased by endotoxin in the lungs, brain, spleen, and FA, but were decreased in the liver. Activities of superoxide dismutase and catalase were decreased in the liver and spleen, but were increased in the lungs, brain, and FA. These effects of endotoxin were prevented by a selective iNOS inhibitor, phenylene-1,3-bis[ethane-2-isothiourea] dihydrobromide. These data suggest that iNOS-derived NO mediates selective organ-specific effects of endotoxin on OS.

Affirmative effects of iloprost on apoptosis during ischemia-reperfusion injury in kidney as a distant organ.

OBJECTIVE: Apoptosis and its regulatory mechanisms take part in renal ischemia-reperfusion (I/R) injury which can result in acute renal failure and the inhibition of the caspase is considered as a new therapeutic strategy. In this context, we investigated the antiapoptotic and cytoprotective effects of iloprost, a prostacyclin analog, in kidney as a distant organ. METHODS: Wistar albino rats were randomized into five groups (n = 12 in each) as sham, ischemia, I/R, iloprost (10 µg kg(-1)), and I/R + iloprost (10 µg kg(-1)). A 4 h reperfusion procedure was carried out after 4 h of ischemia. Caspase-8 was evaluated for death receptor-induced pathways, whereas caspase-9 was evaluated for mitochondria-dependent pathways and caspase-3 was investigated for overall apoptosis. Superoxide dismutase (SOD) enzyme activity and nitrite content as an indicator of nitric oxide (NO) production were also analyzed in kidney tissues. RESULTS: Caspases-3, -8, and -9 were all significantly elevated in both ischemia and I/R groups compared to the sham group; however, treatment with iloprost reduced caspases-3, -8, and -9. SOD enzyme activity was attenuated by iloprost when compared to ischemic rats. The different effects of NO were found which change according to the present situation in ischemia, I/R, and treatment with iloprost. CONCLUSIONS: These findings suggested that iloprost prevents apoptosis in both receptor-induced and mitochondria-dependent pathways in renal I/R injury and it may be considered as a cytoprotective agent for apoptosis. Understanding the efficiency of iloprost on the pathways for cell death may lead to an opportunity in the therapeutic approach for renal I/R injury.

Effects of intravitreal bevacizumab in repeated doses: an experimental study.

PURPOSE: To evaluate the effects of repeated 1.25-mg intravitreal bevacizumab injections on cornea and uveoretinal tissues using histologic and biochemical analyses. METHODS: Twenty-four New Zealand albino rabbits were used. Twelve rabbits received an injection of bevacizumab in their right eyes three times with an interval of 25 days (Group 1); their contralateral eyes served as controls (Group 2). Six rabbits had an injection of vehicle in both eyes (Group 3), with the same regimen as bevacizumab, and six rabbits' eyes were used as a sham group (Group 4). Enucleated eyes were used for histologic and biochemical analyses, which included the activities of caspase 3 and 8 enzymes, glutathione content, catalase activity, and malondialdehyde content. RESULTS: No inflammation in aqueous humor and no sign of corneal or uveoretinal toxicity was found in bevacizumab-injected eyes. The difference of activity of corneal caspase 8 enzyme between Groups 1 and 2 and between Groups 1 and 4 was statistically significant (P < 0.05). In the uveoretinal tissue, in Group 1, the activities of caspase 3 and 8 enzymes were the lowest, and uveoretinal malondialdehyde content was also significantly lower than Group 4. CONCLUSION: A repeated dose of intravitreal bevacizumab injection did not cause a toxic effect on cornea and uveoretinal tissue. Biochemically, it also did not cause any apoptosis, oxidative reaction, or lipid peroxidation. Instead, bevacizumab injection caused a considerable decrease in the apoptotic enzyme activities and lipid peroxidation in the uveoretinal tissue. Further studies are needed to be conducted for possible detrimental side effects and apoptotic and oxidative effects of repeated bevacizumab injections on both the injected and the contralateral eyes.

The effect of different treatment modalities on oxidative stress in COPD.

INTRODUCTION: Oxidant/antioxidant interactions are known to be important processes in the pathogenesis of chronic obstructive pulmonary disease (COPD). We aimed to evaluate the effects of corticosteroids (CS), and N-acetylcysteine (NAC) on plasma oxidant/antioxidant levels in patients with COPD. METHODS: This study utilised a single-blind, randomised, placebo-controlled, parallel-group methodology. We enrolled 58 patients with stable COPD and 30 healthy controls with similar demographic profiles. The patients with COPD were randomly divided into three treatment groups. Group 1 received basal treatment (regular ipratropium bromide and beta-2 agonist as needed), placebo CS and placebo NAC. In addition to basal treatment, group 2 received oral CS (methylprednisolone 40 mg/day) and placebo NAC. Group 3 received basal treatment plus NAC (600 mg/day) and placebo CS. Each group received treatment for 15 days. We measured plasma malondialdehyde (MDA) and superoxide dismutase (SOD) at the start and the end of study. RESULTS: Post-treatment plasma MDA levels were significantly lowered only in group 2 (P=0.004). No significant differences were found with respect to erythrocyte SOD levels. CONCLUSION: This study demonstrates that oral CS, by aiding the oxidant/antioxidant system, may offer a new therapeutic option in COPD treatment.

Oxidant-antioxidant balance in patients with COPD.

The goal of this study was to evaluate the role of oxidant-antioxidant balance in the pathogenesis of COPD. We included 30 healthy nonsmokers [24 male, 6 female; mean age (yr) +/- SD: 62.4 +/- 9.3], 30 healthy smokers [27 male, 3 female; mean age (yr) +/- SD: 58.7 +/- 6.0], 71 patients with stable COPD [68 male, 3 female; mean age (yr) +/- SD: 63.5 +/- 7.9], and 31 patients with COPD exacerbation [30 male, 1 female; mean age (yr) +/- SD: 64.2 +/- 7.3]. In all study groups the peripheral venous blood samples were taken for plasma malonyldialdehyde (MDA), a parameter of lipid peroxidation caused by the oxidants, and erythrocyte superoxide dismutase (SOD), an antioxidant enzyme. The mean plasma MDA level was higher in healthy smokers and in patients with COPD than in healthy nonsmokers (p < 0.05), and erythrocyte SOD enzyme activity in patients with COPD exacerbation (1048.2 +/- 226.5 Ug/Hb) was significantly higher than in healthy nonsmokers (947.9 +/- 198.0 Ug/Hb) (p < 0.05). Although mean erythrocyte SOD enzyme activity in healthy smokers and patients with stable COPD was higher than in healthy nonsmokers, the difference was not statistically significant. We found that healthy smokers and stable and exacerbated COPD patients had an impairment in oxidant-antioxidant balance. We suggested that new therapeutic interventions, which may repair the impaired oxidant-antioxidant balance in COPD, are needed to prevent the development of COPD.

The effect of human growth hormone on superoxide dismutase activity, glutathione and malondialdehyde levels of hypoxic-ischemic newborn rat brain.

OBJECTIVES: We investigated the effect of human growth hormone (GH) on newborn rat brain superoxide dismutase, glutathione and malondialdehyde (MDA) levels in hypoxic-ischemic (H-I) newborn rats. METHODS: Fourty-eight 7 days old newborn rats were randomized to a healthy (n: 15), H-I (n: 18) and GH administered H-I (GH-H-I, n: 15) group. Permanent, left common carotid ligation was performed in the H-I groups. In the GH-H-I group, 50 mg/kg human GH (Norditropin Simplex, Novo Nordisk A/S) was administered subcutaneously just before carotid artery ligation. Two hours after ligation, rats were subjected to 2 h of hypoxemia and then were decapitated. Right and left cerebral hemispheres (CHs) and cerebellum-brain stem (C-BS) were separated. RESULTS: Glutathione levels of each region were not statistically different from each other in and between the groups. Superoxide dismutase levels were higher in C-BSs compared to CHs (for each comparison p < 0.01). CHs and C-BS MDA levels were similar in the control and H-I groups but MDA levels of both CHs of the GH-H-I group were significantly higher than the levels of the H-I group (p = 0.01; p = 0.024, respectively). Left CH MDA level of GH-H-I group was higher compared to left CH MDA of the control group (p = 0.045) while there was no difference between right CHs. In the GH-H-I group, left CH MDA level was higher than the C-BS (p = 0.03). MDA levels of the C-BSs did not differ between the groups (p > 0.05). CONCLUSION: Although we have not evaluated the effect of GH histopathologically, increased lipid peroxidation especially in the H-I (left) hemisphere of the GH treated rats might suggest that GH treatment may be harmful in H-I encephalopathy.

Oxidative-antioxidative system in peripartum acute renal failure and preeclampsia-eclampsia.

BACKGROUND: Preeclampsia-eclampsia and acute renal failure in peripartum women can be the cause of mortality and morbidity. There are many different reports about oxidative-antioxidative systems in preeclampsia-eclampsia. Until now, products of activated oxidative-antioxidative systems were not evaluated in peripartum women with acute renal failure. In this study, our aim was to evaluate the oxidative-antioxidative systems in peripartum women with acute renal failure and/or preeclampsia-eclampsia. METHODS: The study groups consisted of 17 peripartum women (first week of delivery) with acute renal failure (G I), 11 preeclamptic (G II), 11 healthy pregnancy (> or = 30 weeks of pregnancy) (G III), and 11 healthy women (G IV) aged between 18-38 years. Superoxide dismutase (SOD), glutathione peroxidase (GSHPx) in erythrocytes, and plasma malondialdehyde (MDA) levels were measured in all groups. SOD, GSHPx, and MDA levels were also measured at the onset of acute renal failure (G IA), regression of renal dysfunction (G IB) and recovery of renal functions (G IC). RESULTS: MDA levels were 11.95+/-4.25, 9.22+/-3.62, 5.10+/-3.65, 3.40+/-1.27, 4.91+/-2.06, 4.24+/-1.67 mmol/mL in G IA, G IB, G IC, G II, G III, and G IV, respectively. SOD activity in erythrocyte were 3269.23+/-1437.83, 2641.35+/-1411.13, 2056.35+/-1143.11, 924+/-160.04, 1057.91+/-257.03, 861.63+/-243.28 Ug/Hb in G IA, G IB, G IC, G II, G III, and G IV, respectively. GSHPx activity in erythrocyte was 70.17+/-23.52, 58.27+/-23.75, 45.44+/-17.60, 24.48+/-6.77, 26.28+/-7.27, 32.95+/-8.24 Ug/Hb in G IA, G IB, G IC, G II, G III, and G IV, respectively. MDA levels and activities of SOD, GSHPx in erythrocytes were highest in GIA The values of MDA, SOD, and GSH-Px in G IA, G IB, and G IC were significantly different from each other and decreased while regaining of renal functions. Preeclampsia-eclampsia or normal pregnancy did not cause elevation of plasma MDA levels and GSHPx, SOD in erythrocyte. CONCLUSION: Although SOD and GSHPx in erythrocytes and plasma MDA level were found to be similar in healthy women, pregnant women, and preeclamptic women; SOD, GSHPx, and MDA increased at the beginning and decreased during recovery of renal functions in peripartum women with acute renal failure.

The effects of methyl methacrylate on nasal cavity, lung, and antioxidant system (an experimental inhalation study).

Methyl methacrylate (MMA) is a monomer, commonly used in neurosurgery, orthopedic surgery, and in dental clinics. The adverse effects of this monomer are well described in the literature. This study was designed to evaluate the effects of MMA on nasal cavity, lung, and antioxidant status. For this purpose, two experimental groups of rats were exposed to MMA (at 1,000 ppm, 6 h/day, 5 days/week for 4 weeks) by inhalation under poor (group A, n = 12) and normal ventilation (group B, n = 11) conditions. A control group (group C, n = 10) received normal air. Degeneration of olfactory epithelium, bronchopneumonia, interstitial pneumonia, hemorrhage, atelectasis, edema, emphysema, and bronchial epithelial hyperplasia were observed in groups A and B. Emphysema was the most common lesion. Bronchopneumonia with abscesses was only observed in group A. Glutathione levels were significantly decreased and malondialdehyde levels were significantly increased in group A. No significant difference was observed in superoxide dismutase levels between the groups. The data presented indicate that before using MMA, adequate protection systems should be in place to prevent occupationally related MMA respiratory-tract injuries.