Tehran University Medical Journal

Background: In recent publications, several mechanisms have been implicated in gentamicin (GM) nephrotoxicity. Reactive oxygen species have been proposed as one of the causative factors of the drug renal side effects. This study was designed to evaluate the protective effects of the antioxidant vitamins against GM-mediated nephropathy in insitu isolated rat kidneys.

Methods: Male Sprague-Dawley rats were randomly assigned to one of the following groups of seven rats: Group 1 (control) was tyrode perfused kidneys. Group 2 (GM), 200µg/ml gentamicin was added to the perfusate. Group 3 (GM + Vit C), the same as group 2 but vitamin C (200 mg/L) was added to the drinking water for 3 days and 100 mg/L to the perfusate. Group 4 (GM + Vit E), the same as group 2 but vitamin E (100 mg/100 g BW, ip) was injected 12 h before experiments. Group 5 (GM + Vit C + Vit E) the same as group 2 but Vit E and C were co-administered (same as Group 3 & 4). Urinary N-acetyle-B-D-glucosaminidas (NAG) and renal cortex superoxide dismutase (SOD) levels were measured and tissue histological evaluations were performed.

Results: Gentamicin caused a significant nephrotoxicity demonstrated by increase in urinary NAG. Decline in SOD contents were observed comparing to controls. Vit C or Vit E inhibited the gentamicin-induced increased releases of NAG into urine but did not show a significant effect on the SOD levels.  

Conclusion: Co-administration of VitC&E significantly prevented the GM nephrotoxicity demonstrating by preservation of SOD levels and prevention of increase in urinary enzyme activities. Histological studies of renal tissues provided additional evidences for protective effects of antioxidant vitamins. We concluded that moderate doses of Vit C & E have protective effects in gentamicin nephrotoxicity and co-administration of these vitamins have additional beneficial effects.

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.

Normal 0 false false false EN-GB X-NONE AR-SA MicrosoftInternetExplorer4 Background: Varicocele is a major cause of male infertility, but its pathophysiology is unclear. Recent studies declare that fertile varicocele people with normal semen analysis are also at risk of loss of infertility. The exact mechanism by which varicocele damages spermatogenesis is still unknown. Some studies have reported increased Reactive Oxygen Species (ROS) is a major factor in semen of men with varicocele. The aim of this study was to investigate whether the source of elevated ROS is intracellular or not. In addition, we studied Mitochondrial Membrane Potential (MMP), viability, antioxidant activity, sperm count and motility in these rats.
Methods: The study group consisted of 28 male rats divided in four groups: control, sham, varicocele 1, varicocele 2, Experimental varicocele was established by partial ligation of the left renal vein in last two groups. Animals were sacrificed two and six months after surgery and dilation of the internal spermatic veins was observed. Then, superoxide anion production and Mitochondrial Membrane Potential were evaluated by Flow cytometry sperm characteristics were evaluated by Flow cytometry. Sperm superoxide anion production was assessed by the dihydroethidium and Mitochondrial Membrane Potential with rhodamin 123.
Results: Our results showed intracellular superoxide anion production significantly increased and Mitochondrial Membrane Potential, viability, sperm count and motility significantly decreased in rats with experimental left varicocele. However, there was no significant difference for seminal plasma antioxidant activity between all groups.
Conclusions: Consequently, our findings suggest that one of the main sources of ROS production is intracellular and we must consider it in treatment.

Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: The effect of ischemia/reperfusion (I/R) injury on kidney has been under investigation for many years. But the changes in liver function and oxidative stress status in renal I/R injury is not well known. Recent studies suggest a crosstalk between liver and kidneys. The aim of the present study was to assess liver changes after induction of various degrees of renal I/R injury.
Methods: This is an experimental study conducted on 20 male rats that were obtained from animal house of Physiology Department. Twenty male rats were subjected to either sham operation or ischemia (30, 45 and 60 min) followed by 60 min reperfusion periods. Blood samples were drawn post-operatively and plasma creatinine, BUN, ALT and AST were measured. Hepatic glutathione (GSH) and FRAP (ferric reducing antioxidant power) levels and the concentration of IL-10 and tumor necrosis factor (TNF) -alpha were evaluated.
Results: Both 45 and 60 min ischemia followed by 1h reperfusion periods resulted in significant increases in plasma creatinine (11.1±1.7mg/dl and 1.24±0.07mg/dl vs 0.55±0.15mg/dl, p<0.05) and BUN (34±3.85mg/dl and 35.0±2.81mg/dl vs 23.75±1.1mg/dl, p<0.05). These rats showed a significant decrease in liver GSH as well as significant increase in TNF-a & IL-10 concentrations.
Conclusion: Renal ischemia causes changes in liver function and oxidative stress status. A minimum of 45 min ischemia is needed to study the effects of renal injury on liver as a remote affected organ.

Background: Seladin-1 protein protects the neural cells against amyloid beta toxicity and its expression decreased in vulnerable regions of Alzheimer's disease (AD) brains. On the other hand, changes in serum levels of S100 have been considered as a marker of brain damage in neurodegenerative diseases. Furthermore, this study was carried out to determine the relation between the change profile of serum S100&beta protein levels and hippocampal Seladin-1 gene expression in a rat model of sporadic AD. Methods: In this experimental study that established in Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Science, from March 2011 to April 2013, 72 animals were randomly divided into control, 4, 7, 14, and 21days ICV-STZ/Saline administrated rats. Alzheimer's model was induced by intracerebroventricular (ICV) injections of streptozotocin (STZ) [3 mg/kg] on days 1 and 3. Serum levels of S100&beta and hippocampal Seladin-1 gene expression were evalu-ated in experimental groups. The initial and step-through latencies (STL) were deter-mined using passive avoidance test. Results: Serum levels of S100&beta were significantly different between the STZ-7 day and STZ-14 day groups in comparison with the control, saline and STZ-4 day groups. As well as, there was a significant difference between the STZ-7 day group in comparison with the STZ-14 day and STZ-21 day groups (P=0.0001). Hippocampal Seladin-1 gene expression in STZ-14 day and STZ-21 day groups significantly decreased as compared to the control, saline and STZ-4 day groups (P=0.0001). However, significant correla-tion was detected between serum S100&beta protein decrement and Seladin-1 down regula-tion (P=0.001). Also, the STL was significantly decreased in 21 days ICV-STZ adminis-trated rats as compared to the control or saline groups (P=0.001). Conclusion: Monitoring the changes of serum S100&beta protein levels by relationship with changes in hippocampal Seladin-1 gene expression can be a useful indicator of neu-ronal damage in patients with Alzheimer's disease.