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Background: Vanadium (V) is a candidate to decrease the serum level of glucose in diabetic animal model. However, it affects the lipid peroxidation and antioxidant activity so could make nephrotoxicity and hepatotoxicity. In this study, the protective role of vitamin C as an antioxidant on nephrotoxicity and hepatotoxicity induced by vanadyl sulfate was investigated. Methods: This study was designed in 2 protocols. There were 3 groups in protocol 1 that received saline (group 1), saline daily for 7 days plus single dose of vanadyl sulfate (50 mg/kg intraperitoneally) in day 2 (group 2), or vitamin C (250 mg/kg intraperitoneally) daily for 7 days and single dose of vanadyl sulfate (group 3). There were 2 groups in protocol 2 that received saline plus single dose of vanadyl sulfate (50 mg/kg intraperitoneally) in day 2 (group 4) or vitamin C (250 mg/kg intraperitoneally) daily for 2 days plus single dose of vanadyl sulfate (group 5). At the end of experiment, blood samples were collected to measure serum level of blood urea nitrogen (BUN), creatinine (Cr), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP), and all animals were sacrificed for histopathology investigation and determination of kidney tissue damage score (KTDS). Findings: In protocol 1, BUN/Cr ratio, kidney weight (KW), and KTDS decreased significantly in vanadyl sulfate plus vitamin C group in comparison with vanadyl sulfate plus saline group (P < 0.05). In addition, serum level of AST and ALP significantly decreased in vanadyl sulfate plus vitamin C group. In protocol 2, not only similar results were not observed, but also vitamin C increased the side effects of vanadyl sulfate. Conclusion: Administration of vitamin C as a potent antioxidant could decrease the vanadium-induced toxicity. So, as vanadyl sulfate can be used for diabetic model in laboratory, vitamin C can be useful to decrease the vanadium-induced nephrotoxicity and hepatotoxicity, too.

The angiotensin 1-7 (Ang 1-7), is abundantly produced in kidneys and antagonizes the function of angiotensin II through Mas receptor (MasR) or other unknown mechanisms. In the current study, the role of MasR and steroid hormone estrogen on renal blood flow response to Ang 1-7 administration was investigated in ovariectomized (OV) female rats. OV female Wistar-rats received estradiol (500 μg/kg/week) or vehicle for two weeks. In the day of the experiment, the animals were anesthetized, cannulated, and the responses including mean arterial pressure, renal blood flow (RBF), and renal vascular resistance at the constant level of renal perfusion pressure to graded infusion of Ang 1-7 at 0, 100 and 300 ng/kg/min were determined in OV and OV estradiol-treated (OVE) rats, treated with vehicle or MasR antagonist; A779. RBF response to Ang 1-7 infusion increased dose-dependently in vehicle (P dose

Background: Nephrotoxicity is the main side effect of cisplatin (CP)-therapy which is induced by oxidative stress. Nephrotoxicity is gender related and limits the cisplatin treatment. Therefore, it is essential to prevent or to ameliorate cisplatin-induced nephrotoxicity via administration of supplementations. This study was designed to investigate the effect of L-arginine (L-Arg) prophylaxis and treatment on preventing cisplatin-induced nephrotoxicity in male and female rats. Methods: Sixteen male and twenty female Wistar rats were divided into eight groups. Groups 1 (male) and 5(female), as positive control groups, received cisplatin (2.5 mg/kg/day; Intraperitoneally) for a week. Groups 2 (male) and 6 (female) received L-arginine (150 mg/kg/day; Intraperitoneally) as prophylaxis for 3 days, and cisplatin was administered from the day 3 for a week. Groups 3 (male) and 7 (female) received L-arginine, as prophylaxis for 3 days; and cisplatin was administered from the day 3, for a week, without withdrawal of daily L-arginine administration. Groups 4 (male) and 8 (female) received cisplatin and L-arginine simultaneously for a week. On the day 10, blood samples were taken and kidneys were prepared for histopathological investigation. Findings: L-arginine administration did not changed the measured parameters from positive control group in females. Simultaneous administration of cisplatin and L-arginine decreased serum levels of blood urea nitrogen and creatinine as well as intensity of renal tissue damage in comparison with positive control group in males (P < 0.05). In addition, it ameliorated kidney weight in comparison with positive control group in male, insignificantly (P = 0.20). No significant difference was observed in tissue nitrite level among male groups and L-arginine treated male groups had body weight loss more than positive control group (P < 0.05). Conclusion: Simultaneous administration of L-arginine, as nitric oxide precursor, and cisplatin could ameliorate cisplatin-induced nephrotoxicity in male gender through improving endothelium function.

Background: The aim of this study was to evaluate the protective role of short hydration against nephrotoxicity induced by cisplatin (CDDP). Materials and Methods: Twenty-two patients (13 men and 9 women) under CDDP therapy were enrolled in this retrospective study between 2009 and 2014. The CDDP was given in 500 ml of isotonic solution, and before and after CDDP administration, the patients received 10mEq potassium chloride15% and 1gr magnesium sulfate in 1000 ml isotonic saline. Renal parameters were evaluated on the first day of each cycle of CDDP therapy. Results: Median cumulative CDDP dose was 465 mg/m2. Based on renal parameters, the prevalence of CDDP-induced nephrotoxicity (CIN) was 22.7%, while no hypokalemia and hypomagnesemia were observed. Conclusion: Short hydration accompanied with potassium chloride and magnesium sulfate may decrease the risk of CIN.

Background: Nephrotoxicity is the major side-effect of cisplatin (CDDP), and it is reported to be gender-related. We evaluated the effects of pomegranate flower extract (PFE) as an antioxidant on CDDP-induced nephrotoxicity in female rats. Methods: Twenty-three adult female rats in four groups treated as following. Groups 1 and 2 received PFE at doses of 25 and 50 (mg/kg/day), respectively, for 9 days, and from day 3 on, they also received cisplatin (CDDP) (2.5 mg/kg) daily. Group 3 was treated as group 1 expects saline instead of PFE, and group 4 received PFE (25 mg/kg/day) alone. Results: Cisplatin alone increased the serum levels of blood urea nitrogen, creatinine, and nitrite; and kidney tissue damage score and kidney weight. However, PFE not only did not ameliorate the induced nephrotoxicity, but also aggravated renal tissue damage. Conclusions: Pomegranate extract as an antioxidant did not ameliorate CDDP-induced nephrotoxicity in female rats.

Background: Gentamicin (GM) is used as antibiotic for Gram-negative infections, but its administration is limited due to a side-effect of nephrotoxicity. It was attempted to investigate the effect of Althaea officinalis flower extract (AOFE) against nephrotoxicity induced by GM in male rats. Methods: 30-year-old male Wistar rats were divided into five groups. Group 1 as a negative control group received AOFE 250 mg/kg/day. Groups 2-5 received saline, AOFE 50 mg/kg/day, AOFE 250 mg/kg/day, and AOFE 500 mg/kg/day for 9 days, respectively, and GM (100 mg/kg/day) was added from the 3 rd day on. At the end of the experiment, blood samples were obtained, animals were sacrificed, and the kidneys were removed immediately. Results: Gentamicin (in group 2) significantly increased serum levels of blood urea nitrogen and creatinine as well as the pathological damage score (P < 0.05) when compared with group 1. Low dose of AOFE did not decrease the nephrotoxicity induced by GM while the high dose of AOFE aggravated renal toxicity (P < 0.05). Conclusions: Although AOFE acts as an antioxidant, at the doses used in the current study did not ameliorate nephrotoxicity induced by GM.

Background : The angiotensin II (Ang II) receptor 2 (AT2R) and angiotensin 1-7 receptor (masR) expression in the kidney are gender-related. We attempted to compare the response of nitric oxide (NO) production to Ang II administration, with and without AT2R and masR blockades, using A-779 and PD123319 in male and female rats. Methods: Anesthetized and catheterized male and female Wistar rats were subjected to one-hour continuous infusion of Ang II (~20 μg/kg/hour), with and without masR and AT2R blockades. The level of the NO metabolite (nitrite) was measured before and after the experiment in rat serum and in the homogenized kidney tissue. Results: The basal data indicated that no sex difference in the serum level of nitrite could be detected before Ang II infusion. However, administration of Ang II in male and female rats caused a gender difference in the nitrite level, which resulted in the serum level of the nitrite significantly increasing in males ( P < 0.05) when compared with the females. In addition, masR blockade or co-blockade of masR and AT2R in male rats abolished the gender difference related to the effect of Ang II on nitrite production. In the presence of masR and AT2R, or when masR alone was blocked, the level of nitrite in the kidney, in response to the Ang II infusion was not significantly different between the two sexes. On the contrary, masR and AT2R co-blockades significantly decreased the kidney nitrite concentration response to Ang II administration in both male and female rats ( P < 0.05), but no sex difference was detected. Conclusions: The renal vasculature of male rats may provide more response to Ang II administration-induced NO, which is dependent on masR and AT2R. During dual masR + AT2R blockades, the kidney NO formation wasreduced in a non-gender related manner.

Background: Endometriosis is known as one of the most common disease in women of reproductive age. Due to important role of vascular endothelial growth factor (VEGF) in neo-vascularization for the implantation of endometrial cell, and also presence of different studies reported VEGF level in the serum and peritoneal fluid (PF) in endometriosis patients, this study was designed to determine the serum and PF levels of VEGF in endometriosis patients, and to compare with normal subjects. Materials and Methods: In this descriptive study, 179 women subjected to laparoscopy for the evaluation of infertility or pelvic pain were allocated into the following two groups: group I: different types of endometriosis patients (n=90) and group II: non-endometriosis patients (n=89). The PF from pelvis and venous blood samples were obtained. The VEGF concentration of the serum and PF were measured using enzyme immunoassay kit and were compared using t test. Results: The level of VEGF in serum was significantly less than that in PF in both groups (p=0.00). However, endometriosis patients had significantly higher level of VEGF in peritoneal fluid than non-endometriosis patients (p=0.043). Conclusion: According to our findings, endometriosis is not associated with change in the level of circulating VEGF.

Background: Acute kidney injury (AKI) has been recognized as one of the most complex clinical complications in modern medicine, and ischemia/reperfusion (I/R) injury is well-known as a main reason of AKI. In addition, AKI leads to important systemic consequences such as acute lung injury. This study was designed to investigate the role of erythropoietin (EPO) on kidney function makers and tissue damage; and lung endothelial permeability and lung water content (LWC) in bilateral renal I/R injury model in rats. Methods: Male Wistar rats were randomly divided into three groups of sham, I/R, and I/R treated with EPO (I/R + EPO) groups. The I/R and I/R + EPO groups were subjected to bilateral renal I/R injury; however, only the I/R + EPO group received EPO (500 IU/kg, i.p.) 2 h before ischemia surgery, and the same dose was continued once a day for 3 days after ischemia. The sham group underwent a surgical procedure without ischemia process. Results: The blood urea nitrogen (BUN) and serum creatinine (Cr) levels, kidney tissue damage score (KTDS), and kidney weight (KW) per 100 g body weight significantly increased in I/R group ( P < 0.05). EPO administration decreased levels of BUN and Cr significantly ( P < 0.05), and KTDS and KW insignificantly ( P = 0.1). No significant differences in kidney and serum levels of malondialdehyde, and lung vascular permeability and LWC were observed between the groups. The serum and kidney levels of nitrite were not significantly different between I/R and sham groups; however, administration of EPO increased the renal level of nitrite ( P < 0.05). Conclusions : EPO protected the kidney against I/R injury; however, it may not protect the lung tissue from the damage induced by renal I/R injury in rats.

Background: Nephrotoxicity is the most common adverse effect of cisplatin therapy in clinic, which also disturbs the nitric oxide system. Cisplatin-induced nephrotoxicity may be gender-related; nevertheless, no information has been well documented regarding the gender-specific influences of cisplatin on nitric oxide metabolites. In order to narrow this gap, this study was designed to determine the gender difference in the serum levels of total nitric oxide metabolites (NOx), nitrite, and nitrate in cisplatin-induced nephrotoxicity in rats. Methods: 25 male and female rats were randomly divided into 4 groups. The male groups 1 and 3 were received saline (control) and a single dose of cisplatin (7 mg/kg), respectively. The female groups 2 and 4 also received similar treatments. One week later, the blood samples were obtained and the animals were sacrificed for pathological investigation. Findings: The serum levels of NOx (group 1 = 22.43 ± 3 mmole/liter, group 3 = 50.71 ± 7.52, P < 0.05), and nitrite (group 1 = 13.2 ± 2.1 mmole/liter, group 3 = 37.7 ± 4, P < 0.05) in male animals treated with cisplatin was significantly higher than the control group. Such finding was not seen in female rats. The intensity of kidney tissue damage in male rats was also more marked compared with the female animals. Conclusion: The effect of cisplatin on nitric oxide metabolites could be gender related, and nitrite is more influenced by cisplatin than nitrate. More studies may be needed for clarifying the exact mechanisms. Keywords: Cisplatin, Adverse effects, Nitric oxide, Sex, Rats

Background: Gentamicin (GM) is a commonly used aminoglycoside, however, renal toxicity has limited its usage. This study was designed to evaluate the curative and protective effects of Zingiber officinale (ginger) against gentamicin tubular toxicity in rats. The phenolic and flavonoid components and antioxidant activity of ginger were also evaluated. Methods: In a preclinical study, 50 male Wistar rats were designated into 5 groups of 10 and treated as follows: Group I: vehicle. Group II: 200 mg/kg/d of ginger for 3 days then, GM (80 mg/kg) for 7 days. Group III: 200 mg/kg ginger orally for 3 days, then ginger plus GM for 7 days. Group IV: GM for 7 days. Group V: GM for 10 days. Group VI: GM for 7 days, then 200 mg/kg ginger orally for 10 days. At the end of the study, the animals were sacrificed and their kidneys were histologically evaluated. Results: Ginger could prevent degeneration of the renal cells and reduce the severity of tubular damage caused by gentamicin. However, it could not regenerate the GM degeneration. Conclusions: The results indicate that ginger is effective as a prophylaxis agent, but has not curative effect.

Background: The aim of this study was to test the potential properties of metformin (MF) to protect the kidney from gentamicin (GM)-induced renal toxicity. Materials and Methods: In this preclinical study, 50 male Wistar rats were randomly divided into five groups of 10 rats in each. In the first group (group I), they were kept in the same condition as others without receiving drugs for 10 days. In group II, the rats were injected intraperitoneally with 100 mg/kg/day of GM for 10 consecutive days. Group III rats received 100 mg/kg/day MF orally for 10 days. In group IV, the rats received GM (100 mg/kg; intraperitoneally) for 10 days and 100 mg/kg/day MF orally for the next 10 days. In the last group (group V), the rats received a combination of GM 100 mg/kg/day intraperitoneally and MF 100 mg/kg/day orally for 10 days simultaneously. Serum blood urea nitrogen (BUN) and creatinine (Cr) values were measured and renal tissues of the animals were processed for light microscope examination. Results: The levels of BUN in groups II, IV, and V, and also the serum level of Cr in groups II and V were increased significantly after the experiment. Furthermore, post-treatment with MF or co-treatment with MF could prevent the elevation of serum BUN and Cr induced by GM and also attenuates the damage score (P < 0.05). Conclusions: MF may prevent or ameliorate GM-induced acute renal failure, and therefore it might be beneficial in patients under treatment with this medicine.

Background: After reestablishment of blood flow to ischemic limb recirculation of free radicals may cause ischemia-reperfusion injury in many organs. This study designed to investigate effects of hydrocortisone and alprostadil distant injury to kidneys by both measuring biochemical markers of oxidative stress and histopathologic examination in an experimental rat model of hind limb ischemia-reperfusion. Materials and Methods: This study conducted in Isfahan University of Medical Sciences during 2011–2012. Ischemia was established by infra renal aortic clamping for 60 min in 32 male Wistar rats. Animals were divided into those receiving alprostadil (group ischemia-reperfusion plus alprostadil (IR/A), n = 8), those receiving hydrocortisone (group ischemia-reperfusion plus hydrocortisone (IR/H), n = 8), control group (group ischemia-reperfusion (IR), n = 8), and sham group (n = 8). After 120 min of reperfusion both kidneys were removed. Levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) as indirect markers of oxidative injury was measured. Finally all data in different groups were compared using the analysis of variance (ANOVA) test by Statistical Package for Social Sciences (SPSS) version 16. Results: Administration of alprostadil or hydrocortisone does not improve the biochemical parameters of oxidative injury including MDA and SOD. However, statistically significant difference was seen in GSH level among sham and IR groups. Mean (± standard deviation (SD)) concentration of GSH in IR, IR/A, IR/H, and sham groups were 1028.77 (72.65), 924.82 (70.66), 1000.28 (108.77), and 846.69 (163.52), respectively (P = 0.015). Histopathological study of specimens did not show any significant changes between groups. Conclusion: Alprostadil and hydrocortisone do not improve the kidney GSH, SOD, and MDA level and kidney releases its GSH reserve during ischemia-reperfusion event, and another point is that, 3 h of ischemia-reperfusion does not develop injury in kidney.

Objectives: Cisplatin (CP) is used as the commonest drug to treat solid tumors. It is accompanied by a nephrotoxicity side effect. The main objective of this study is to investigate the protective role of magnesium (Mg) supplementation in CP-induced nephrotoxicity in a rat model. Methods: Twenty-nine Wistar rats were randomly assigned to four groups (1-4). Groups 1-3 received 20, 80, and 200 mg/kg magnesium sulfate respectively, for 10 days, but on day 3, a single dose of CP (7 mg/kg, i.p.) was also injected. Group 4 (positive control group) received the same regimen of Groups 1-3 except saline instead magnesium sulfate. One week after CP administration, blood samples were obtained and all animals were killed for kidney histopathological investigations. Results: All CP-treated animals lost weight, and the percentage of weight loss in Group 1 (low dose Mg sulfate treated) was significantly higher compared with the positive control group (Group 4, P < 0.05). The increase in blood urea nitrogen (BUN) and creatinine (Cr) levels in serum in Group 1 were more than those in other groups ( P < 0.05). No statistical differences were observed in serum magnesium, nitrite, and total protein levels among the groups. The kidney tissue damage in Groups 1-3 was not significantly different when compared with Group 4. Moreover, the kidney and testis weights in Group 1 were significantly greater than those in the positive control group (P < 0.05). Conclusion: Regarding the BUN and Cr levels in the serum, kidneys weight, and the histopathological study, the low dose of Mg supplementation intensifies kidney toxicity and renal dysfunction in CP-induced nephrotoxicity in the rat model. However, the protective role of Mg with moderate and high doses is not certain.

BACKGROUND: Colloid Osmotic Pressure (COP) is an important factor in the fluid balance of body compartments. COP is related to Total Protein (TP) concentration and Albumin: Globulin Ratio (A/G). The A/G was not included in pervious empirical models, and therefore the main objective of this study was to develop a mathematical model to determine the COP in terms of TP concentration and A/G. METHODS: Sera with different A/G were prepared in-vitro, and COP was measured directly using colloid osmometer. The relationship between COP, TP concentration and A/G were determined mathematically. The validity of developed empirical models was confirmed by statistical comparison between measured and calculated COP in 122 serum samples obtained from hospitalized patients and healthy individuals. RESULTS: By non-linear regression, the following relationships were found between COP, TP concentration and A/G. All coefficients were statistically significant (p

Background: Acute kidney injury (AKI) is a complex syndrome defined as rapid decrease in glomerular filtration rate and therefore, retention of metabolic waste substances. The risk of AKI in candidates for coronary artery bypass graft (CABG) surgery usually is highlighted. The main objective of this study was to determine the AKI prevalence after CABG surgery. Methods: This observational study was performed on 1534 patients undergoing CABG surgery in Sina cardiac surgery center, Isfahan, Iran during 2006 till 2010. The information of patients was collected from hospital data sheet and recorded in a questionnaire. AKI was determined by laboratory data. Findings: 76.4% of the patients were men. The patients were 60.8 ± 8.9 years old with the average body mass index (BMI) of 27.0 ± 4.3 kg/m2. The prevalence of AKI was 49.1%. In overall, the hospital mortality rate was 2.7% and 0.7% of patients were assigned for dialysis. Conclusion: Our results indicated that the prevalence of AKI was considerably high. Special attention and hospital take cares are needed to reduce this prevalence.