Tehran University Medical Journal

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Background: Ureteral obstruction, leading to urinary stasis and elevated pressure in the proximal part of urinary tract, causes progressive renal dysfunction. This study was designed to evaluate the status of oxidative stress and metabolic defect in acute unilateral ureteral obstruction (UUO).

Methods: Experiments were performed on three groups of male Sprague-Dawley rats (n=10 in each group). In the UUO group, rats were lightly anesthetized by ether and the left ureter was occluded by means of a sterile surgical procedure. Twenty-four hours after UUO-induction, both kidneys were removed and stored at -70 °C. In the sham group, anesthesia and surgery were performed without ureteral occlusion, and the control group received no surgical procedure. The kidney samples were assessed to measure the levels of ATP and ADP by the luciferin-luciferase method for determining metabolic status. In addition, the levels of malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP) of the kidneys were measured to evaluate the redox state. Data are expressed as means ±SEM per gram of kidney weight (gKW). The comparisons were performed using paired t-test for intra-group analysis, and ANOVA followed by Duncan's post-hoc test and then LSD test for inter-group analysis. Significance was taken at p<0.05.

Results: The comparisons between the UUO and sham groups indicated that 24 hours of UUO increased levels of MDA (51.42±1.86 vs. 38.64±1.02 nmol/gKW, respectively p<0.001) and ADP (0.67±0.04 vs. 0.47±0.045 µmol/gKW, respectively p<0.01), but decreased levels of FRAP (2.44±0.18 vs. 4.28±0.27 µmol/gKW, respectively), ATP (1.09±0.10 vs. 2.26±0.19 µmol/gKW, respectively) and ATP/ADP ratio (1.64±0.14 vs. 5.11±0.56, respectively) in the obstructed kidneys, all p<0.001. In the non-obstructed kidneys, the levels of ATP and ADP were higher (p<0.01 and p<0.001, respectively), while the levels of MDA and ATP/ADP ratio were equal to those of the sham group.

Conclusion: Twenty-four hours of acute UUO induces oxidative stress and reduces the aerobic metabolism in obstructed kidneys, whereas non-obstructed kidneys with a normal redox state show the higher levels of metabolism.

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Background: The risk of atherosclerosis and cancer is high in hemodialysis (HD) patients. There is evidence that HD causes oxidative stress. However, the causative factors of oxidative stress are unknown. It has been suggested that HD imposes an additional oxidative stress on patients with chronic renal failure by activation of granulocytes on dialyzer membranes resulting in an imbalance between oxidants and antioxidants. In this regard, a number of reports, either measuring specific analytes or enzymes, or estimating the total antioxidant activity of the plasma have given contradictory and inconclusive results. To investigate the oxidative stress status in Iranian HD patients, in this study, we evaluated GSH and FRAP levels along with Ca and pH in the blood of these patients.

Methods: Along with 20 healthy age and gender matched control subjects, 24 patients underwent dialysis, three times per week, for four hours in each session. Before and after dialysis, blood was taken for biochemical and liver function tests and to evaluate oxidative stress markers and measure Ca and pH levels.

Results: There was a significant decrease in FRAP and GSH levels after dialysis compared to those before treatment. Dialysis caused an increase in pH and Ca levels compared to levels in control subjects after dialysis.

Conclusion: In general, before dialysis, there is a balance between oxidants and antioxidants however, due to higher levels of oxidants as well as the possible binding of antioxidants to the dialyzer membrane during dialysis, an imbalance occurs. The instability in the balance of oxidants and antioxidants may be the major cause of cellular oxidative damage found in HD patients. This study indicates that there is a significant level of oxidative stress in renal chronic patients and this stress is augmented by dialysis. Antioxidant therapy should be considered in these patients.

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Background: Ureteral obstruction has been shown to induce renal oxidative stress, suppressed energy metabolism and defected acid excretion. This study was aimed to examine the improving effects of L-carnitine, a facilitating cofactor for mitochondrial oxidation of fatty-acids as well as a scavenger of free-radicals, and -tocopherol as the most potent antioxidant on these renal disorders at early hours following release of unilateral ureteral obstruction.
Methods: The left ureter was ligated in 60 anaesthetised rats, L-carnitine, -tocopherol, or their vehicles (normal saline and olive oil, respectively) were injected (i.p.) in four groups. Each rat was re-anesthetized and cannulated, and ureteral legation was released at exactly 24h after UUO-induction. A 30-min clearance period performed to separately collect urine from both kidneys. The collected urine and arterial blood samples were given to pH-gas analyzer and autoanalyzer, and malondialdehyde (MDA), ATP and ADP levels were assessed in preserved kidneys. There were also sham and control groups (n=8-10 in each).
Results: In the post-obstructed kidney of vehicle-treated groups with respect to the equivalent kidney of sham group, there were increases in MDA (p<0.001), ADP (p<0.01), urinary pH (p<0.001), absolute (p<0.05) and fractional bicarbonate excretions (p<0.01), but decreases in ATP, ATP/ADP (both p<0.001), and urinary PCO2 (p<0.01). -tocopherol could normalize MDA level but did not affect the altered amounts of energy metabolic indices and acid-base excretions, while L-carnitine improved all of them except of decreased urinary PCO2.
Conclusions: Increased bicarbonate-excretion in post-obstructed kidney is due to defected acid-secretion at collecting duct, which is not related to ureteral obstruction-induced renal oxidative stress and suppressed energy metabolism.

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Background: Many chemotherapeutic regimens used in the treatment of cancer generate free radicals that may be a part of their beneficial effects. The aim of this study was to assess the oxidative status in patients undergoing chemotherapy for acute myeloid leukemia (AML).

Methods: Thirty-eight patients with AML (17 female and 21 male patients) with a mean age 34.05±12.49 years were included in the study. All the patients received cytarabine and daunorubicin as their standard induction therapy. Serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and also the erythrocyte superoxide dismutase and glutathione peroxidase activities were measured before and 14 days after chemotherapy.

Results: Plasma malondialdehyde concentrations increased significantly (from a former 2.68±0.89 nmol/ml to 3.14±1.29 nmol/ml) 14 days post chemotherapy (p=0.04). Moreover, the total plasma antioxidant capacity changed from 1.09±0.15 mmol/L to 1.02±0.14 mmol/L (p=0.005). Erythrocyte superoxide dismutase and glutathione peroxidase activity decreased over time from 1157.24±543.61 U/gHb to 984.01±419.09 U/gHb (p=0.04) and 46.96±13.70 U/gHb to 41.40±6.44 U/gHb (p=0.02), respectively.

Conclusion: In this study, an increase in malondialdehyde levels and a decrease in the levels of antioxidant enzymes and total antioxidant capacity were observed. It seems that chemotherapy by cytarabine and daunorubicin generates enormous amounts of free radicals in patients undergoing the treatment for AML. Use of antioxidant supplementation during chemotherapy i is discouraged as it may interfere with the generation of free radicals that may be a part of the therapeutic efficacy of these drugs.

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Background: In a recent study, we were able to demonstrate a role for leukocyte transfer in the induction of liver damage in recipient mice after induction of IR (60 min of bilateral renal artery occlusion and 3 hrs reperfusion) injury in donors. The present study investigates the role of leukocyte transfer in the induction of kidney damage in recipient mice after induction of renal IR injury in donors.

Methods: Mice were divided into two sham and renal IR groups. After anesthesia, leukocytes were isolated from blood and were transferred to the two recipient groups: the intact recipient mice received leukocytes from the sham donor group (Sham recipient) and the intact recipient mice that received leukocytes from IR donor group (IR recipient). After 24 hrs, the recipient mice were anesthetized and blood samples and renal tissues were collected.

Results: Renal malondialdehyde (MDA) increased and glutathione and superoxide dismutase (SOD) decreased significantly in IR recipient group in comparison to sham recipient group. Although renal function tests, including BUN and plasma creatinine were significantly different between IR donor and sham donor groups, but they were not significantly different in two recipient groups. Renal tissues in IR donor group showed extensive damage compared to sham group, but in IR recipients' kidneys, they were different from IR donor tissues despite being different from their respective sham group.

Conclusion: These findings are suggestive of implication of leukocytes in renal tissue damage and oxidative stress after renal IR injury.

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Background: Diabetes mellitus affects numerous intracellular metabolic processes, which are reflected by changes in the concentration of some plasma constituents. Particularly, the disease may indirectly undermine some functions of the nervous system including learning and memory through altering oxidative stress status. On the other hand, probiotics can enhance the antioxidant capacity. This study was designed to evaluate the effects of probiotics on spatial memory, maze learning and indices of oxidative stress in diabetic rats.
Methods: In this experimental study, 40 male Wistar rats were randomly allocated to 4 groups (n=10 for each): Control (CO), Control probiotic (CP), Control diabetic (DC), and Diabetic probiotic (DP). The probiotic supplement, including Lactobacillus acidophilus, Lactobacillus fermentum, Bifidobacterium lactis (334 mg of each with a CFU of ~1010), was administered through drinking water every 12 hours for 8 weeks. Using morris water maze (MWM), spatial learning and memory were evaluated. Serum insulin and oxidative stress indices, including superoxide dismutase (SOD) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), were measured by standard laboratory kits.
Results: Oral administration of probiotics improved impairment of spatial learning (P=0.008) and consolidated memory (P=0.01) in the rats. Moreover, probiotic treatment increased serum insulin (P<0.0001) and serum superoxide dismutase activity (P=0.007) while it decreased their blood glucose (P=0.006) and 8-OHdG (P<0.0001).
Conclusion: Probiotic supplementation reversed the serum concentrations of insulin and glucose along with an increase in antioxidant capacity in diabetic rats. It also improved spatial learning and memory in the animals. Relevancy of the metabolic changes and behavioral functions need to be further studied.

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Background: We are in new era of knowledge and treatment of women with PCOS. We should find management modalities that can improve their life quality. Due to high prevalence of PCOS, and zinc deficiency in Iran, importance of antioxidants such as zinc on treatment and improvement of PCOS complications, and due to the disadvantages of the current treatment for the disease (i.e. OCPs), finding an efficient alternative therapy with no or less side effects seems to be as important as some methods for changing the life style of these women. This study was performed to assess zinc levels in PCOS versus non PCOS patients to determine if zinc can be helpful in PCOS management.
Methods: This is a case-control study which was performed from January 2012-2013 in 100 infertile women aged 20-45 years who were referred to Vali-e-Asr infertility clinic. Fifty patients had PCOS according to Rotterdam Criteria (case group) and 50 were infer-tile women without PCOS (control group). In both group, serum Zinc levels were deter-mined and the data was gathered using the SPSS software and analyzed by descriptive (percent, mean, standard deviation) and analytical 2, ANOVA, Mann-Whitney and Correlation).
Results: Results did not show a significant difference between case group and control group in respect to serum Zinc levels (P>0/05).
Conclusion: Due to no difference between case group and the control one in zinc levels, it seems that zinc supplementation in PCOS patients is not necessarily useful or of clinical importance. Obviously studies with larger sample size can probably define the role of zinc in these patients.

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Background: Approximately 50% to 80% of women experience varying degrees of postpartum depression. Oxidative stress is involved in many diseases, including depression. Common production of lipid peroxidation by oxidative stress is malondialdehyde (MDA). The endocannabinoid system is a nervous regulator and convoy the impression that the circulatory levels of endocannabinoid is significantly reduced in depressed women. The major purpose of this paper was to evaluate activity of the major antioxidant and endocannabinoid index in postpartum depression. Methods: A total of 130 women were entered in a case-control study in 12 Bahman Health Center from April 2011 to August 2011. In 4th to 6th week after delivery, women were equally divided into 2 groups based on Edinburg questionnaire (normal and postpartum depressive women). Serum MDA, total antioxidant capacity (TAC) and RBC catalase levels were determined to investigate the oxidative status. In addition, Mass spectrometry was applied for the analysis of serum anandamide (AEA) and 2-Arachidonoylglycerol (2-AG). Results: Based on Edinburg questionnaire, however, women age, husband age, husband marital number, gravidity, children number, salary and house size have no significant effect on postpartum depression, marital period was significantly increased postpartum depression (P< 0.05). In addition, women education, husband education, wanted or unwanted pregnancy from women, neonatal sex, satisfaction of neonatal sex from women and husbands, breast feeding and delivery have no significant effect on postpartum depression, and women Job (P< 0.001), husband job (P< 0.001), wanted or unwanted pregnancy from husbands (P< 0.05) were significantly changed postpartum depression. Serum MDA and RBC catalase levels were not significantly higher in depress compared with the normal group. TAC was significantly decreased in patients having postpartum depression (P< 0.05). Serum AEA and 2-AG levels were significantly lower in depress compared with the normal group (P< 0.01). Conclusion: Women’s Job, husband’s job, wanted or unwanted pregnancy from husbands and marital period are associated to postpartum depression. In postpartum depression, TAC, AEA and 2-AG are reduced. So it can be concluded that both antioxidant system and endocannabinoid concentration involved in the development of postpartum depression.

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Background: Bone is a hard and dynamic tissue, which continually undergoes remodeling process. Longitudinal growth of bone is mediated by growth plate that is a cartilage structure at the end of long bones. During puberty, along with the closure (ossification) of growth plate, the longitudinal growth of bone will stop. Diazinon is one of the widely used organophosphorus pesticides that have been known to cause damage to the cells and tissues of the body by enhancing oxidative stress. Due to the dynamism and active process, bone and growth plate tissues are suitable models to investigate the effect of diazinon on bone development and bone growth. The aim of this study was to investigate the effects of diazinon on the epiphyseal growth plate width (including the proliferating cells zone and hypertrophy cells zone) of immature rat. Methods: This is an experimental study. This study was performed on 12 immature male in Ferdowsi University of Mashhad in May 2014, Wistar rats that randomly divided into 2 groups: control group and diazinon group. All treatments were done by oral gavage during 28 days. The animals were sacrificed on day 28 and left femur bones were removed for histomorphometric studies of epiphyseal growth plate width. Assessments were done by ImageJ software, version 1.40g (Wayne Rasband, NIH, USA) and the significance of the results were performed by ANOVA analysis and Tukey’s test. Results: Epiphyseal growth plate width of diazinon group was significantly reduced (P=0.0126) in compared to control group. This reduction was associated with reduced of width of the proliferating zone (P=0.0001) and increased width of the hypertrophy zone (P=0.0166). Conclusion: Diazinon leads to reduction in the Epiphyseal growth plate width of immature male rats. Therefore it could be a factor in the impairment of bone longitudinal growth and premature closure of the growth plate.

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Background: Anembryonic gestation (blighted ovum) is the most common identifiable pathology in the first trimester of pregnancy, always leads to miscarriage. Early pregnancy failures from blighted ovum are often due to chromosomal abnormalities and a poor quality of sperm or egg. Oxidative stresses as a factor of disturbance balance between the production of free radicals and antioxidant defenses is involved in the pathogenesis of many diseases, including mouth and throat cancer and cardiovascular disease. Catalase is one of the defensive systems against damages caused by oxidative stress in human. The aim of this study was to compare the activity of salivary catalase in women with blighted ovum and women with history of normal pregnancy.

Methods: This case-control study was performed on 34 patient women with blighted ovum and 34 healthy women as a control group. The study was performed in biochemistry laboratory at the University of Guilan from October 2015 to July 2015. The age range was 20-44 years and 18-45 years in patient and control groups, respectively. Unstimulated saliva samples were collected using spitting method. Catalase activity was measured by evaluating the constant rate of hydrogen peroxide decomposition in patient and control groups.

Results: The patient group matched with healthy subjects in average age and having no other diseases history. The biochemical enzymatic assays indicate that the average catalase activities of saliva in patient and control groups were 14.47±3.8 and 16.42±3.48, respectively. Therefore, the catalase activity was significantly reduced in patient group as compared to the control group (P=0.03).

Conclusion: The obtained results suggested that oxidative stress plays an important role in the pathogenesis of blighted ovum. Therefore, determination the activity of other antioxidant enzymes, in addition to catalse, may be used as a marker for diagnosis of blighted ovum. More studies with larger studied-population is recommended to confidently comment on the results of this study.

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Background: Nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis, fibrosis and liver cirrhosis. The oxidative stress enzymes are the diagnostic markers to prediction of histologic status of liver in nonalcoholic steatohepatitis disease. The aim of the study was to assessment of relationship between serum Zinc (Zn) levels with pathologic manifestation in patients with nonalcoholic steatohepatitis.

Methods: This cohort study was done in patients with nonalcoholic steatohepatitis that had been visited in gastrointestinal clinic of Sina Hospital, Tehran, Iran from April, 2014 to April, 2015. Control group included the patients with no clinical manifestation of nonalcoholic steatohepatitis and normal liver ultrasonography, lab test and liver biopsy. Serum Zn level was measured with atomic absorption spectroscopy. Normal Serum level of Zn was considered 10.7-22.9 µmol/L (70-150 µg/dL) and less than 7 µg/dL was considered as Zn deficiency. Pathological findings were grading according to NAFLD activity score.

Results: One hundred twenty patients were selected for the study in two equal groups. Six and 26 patients were excluded in case and control groups, respectively due to no consent to lab test. Finally, 54 patients (35 male/19 female) and 34 patients (22 male/12 female) in control group were participated in data analysis. The mean age on case and control group was 37.02±9.82 year and 33.24±12.01 year, respectively (P= 0.111). Zn level in case and control groups were 90.82±13.69 and 88.82±13.10, respectively. There were no statistically significant differences between two group in serum Zn level (P= 0.50). Also, there were no statistically significant differences between pathological grading in case group participants (steatosis: P= 0.640; Lobular inflammation: P= 0.882; fibrosis: P= 0.531).

Conclusion: The finding of the study showed no significant association between serum zinc level and hepatic steatosis, lobular inflammation and fibrosis of the liver in nonalcoholic steatohepatitis.

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Breast cancer is the most commonly diagnosed cancer in women worldwide. Enormous advancement has been made over the last decades in understanding the biology of breast cancer. Nevertheless, the molecular mechanisms regulating progression, gaining of invasive and metastatic phenotypes, and therapeutic resistance are still not completely understood. Oxidative stress initiate by disbalance in redox status of body. In this case, increase of free radicals in body cause tissue damage. One of the significant species of free radicals is reactive oxygen species (ROS) that produced by various metabolic pathways, comprising aerobic metabolism in the mitochondrial respiratory chain. They play a serious role in cellular physiology and pathophysiology likewise beginning and evolution of numerous types of cancers. ROS overproduction is deleterious to cells, and considered key-factors for the development of numerous diseases, such as cardiovascular disorders, neurodegenerative diseases, and cancer. Cancer cells are commonly submitted to upper ROS levels that further incite malignant phenotype through motivation to preserved proliferation, angiogenesis, death evasion, invasiveness, and metastasis. ROS impress various signaling pathways, comprising mitogenic pathways and growth factors, and also controls numerous cellular processes, containing cell proliferation, thus stimulates the undisciplined growth of cells which inspires the development of tumors and initiates the progression of carcinogenesis. The importance of ROS on breast cancer development and etiology is being increasingly clarified. Nevertheless, fewer consideration has been given to the progress of redox system-targeted strategies for breast cancer treatment. Augmented oxidative stress caused by reactive species can diminish the body’s antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are core factors in the development of cancer. Bimolecular reactions cause free radicals which create such compounds as malondialdehyde (MDA) and hydroxyguanosine. These substances known as indicators of cancer. In this review, free radicals as oxidizing agents, antioxidants as the immune system, and the role of oxidative stress in cancer, particularly breast cancer, have been investigated by hope that better exploration of the factors involved in the occurrence and spread of cancer will improve the identification of treatment aims.

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Results: The results showed that MDA and The relative wall thickness (RWT) decreased after 8 weeks in HIIT+ supplement and HIIT+placebo groups and TAC level and LVEDd increased significantly (P<0.05). PWd decreased significantly only in the exercise+supplement group (P<0.05). No significant difference between groups in any other variables was detected (P>0.05). Conclusion: Eight weeks of high-intensity interval training alone or with quercetin by reducing oxidative stress(increasing total antioxidant capacity (TAC) and reducing malondialdehyde (MDA) reduces level of concentric pathologic hypertrophy in men with hypertension and coronary heart disease after angioplasty. So that high-intensity interval training with quercetin supplementation has relatively more effects.

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Background: In the present study, we hypothesized that conditioned medium (CM) derived from mesenchymal stem cells attenuates the brain oxidative stress in sepsis induced by the cecal ligation and puncture (CLP) model.
Methods: This study was performed in the Department of Physiology at Tehran University of Medical Sciences from August 2018 to April 2019. Conditioned medium was collected from mesenchymal stem cells isolated from rat's adipose tissues at the second culture passage. Male Wistar rats weighting (220-250 g) were randomly divided into three experimental groups (n=8 each): Sham, Sepsis and CM. Sepsis was induced by cecal ligation and puncture model in the Sepsis and CM groups. Animals in the CM group received the conditioned medium from 5×10⁵ mesenchymal stem cells (2 h after sepsis induction, i. p., 3-5 mL). The systolic blood pressure and O2 saturation were measured 24 h after the treatment. The plasma and brain tissue samples were taken for inflammatory and oxidative stress assessment, respectively.

Results: Septic rats showed a significantly lower systolic blood pressure and O2 saturation level. They also had a significant increase in the plasma inflammatory indices (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6]) and brain malondialdehyde (MDA) content as well as a significant reduction in the brain superoxide dismutase (SOD) activity compared to the Sham group. The CM group had significantly higher systolic blood pressure and O2 saturation level compared to the septic rats. The animals in the CM group showed a significant attenuation in the plasma inflammatory indices (TNF-α and IL-6) and brain MDA content while having a significantly higher brain SOD activity compared to the Sepsis group. Conclusion: Our findings showed that conditioned medium derived from mesenchymal stem cells has protective effects in preventing the inflammatory and oxidative stress status and may be suggested as a promising treatment in patients suffering from sepsis and septic shock.

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