Kidney Malondialdehyde Levels Research Articles

Mildronate ameliorates kidney injury and reduces inflammation in Sickle Cell Disease mice

INTRODUCTION: Sickle cell disease (SCD) is a hereditary hemoglobin disorder characterized by hemolytic anemia, vaso-occlusive crisis and chronic inflammation that affects multiple organs including kidney, liver, brain, spleen, and heart. Renal disease, the most common complication in SCD, is a progressive disease that begins in childhood as glomerular hyperfiltration, then advances to albuminuria, following by a fast decline in glomerular filtration. It may further progress to a renal failure in adults. More than 50% of SCD patients develop chronic kidney disease (CKD), and 14-18% progress to the end-stage kidney disease. Renal injury in SCD results from a cascade of events starting with chronic red blood cells sickling and hemolysis leading to increased blood viscosity, microvascular obstruction and dilation, hypoxia in the medulla, oxidative stress, and inflammation. Mildronate (meldonium) is an anti-ischemic and anti-inflammatory medication approved in Eastern Europe. HYPOTHESIS: We hypothesized that mildronate administration reduces renal medullary hypoxia and decreases oxidative stress and inflammation ameliorating renal injury in SCD mice. METHODS: The study was approved by the Howard University IACUC. Townes SCD mice, expressing human HbS, and control mice, expressing human HbA, were injected with mildronate (400 mg/kg in saline) intraperitoneally or saline as vehicle control over the course of ten days. Blood was collected and used for hematological parameters analysis. Cytokines were measured by Bio-Plex suspension array in plasma. Hypoxyprobe Biotin kit (Hypoxyprobe Inc) was used for visualization of organ hypoxia. The effect of Mildronate on systemic and renal oxidative stress was measured by malondialdehyde (MDA) using ELISA (Abcam). Urinary KIM-1 was measured by TIM-1/KIM-1 ELISA kit (R&D Systems). RESULTS: Mildornate injections did not affect hematological parameters of SCD mice including hematocrit, MCV, MCH, CMCH, erythrocytes and hemoglobin. Mildronate administration resulted in a significant reduction of the circulating pro-inflammatory cytokines IFN-γ, IL-1β and TNF-α and a trend toward reduction of IL-6, and IL-17 in SCD mice. We found higher level of hypoxia in the medulla of SCD mice compared to control mice. Mildronate injections did not reduced hypoxia in renal medulla of SCD mice. Also, mildronate injections did not change MDA levels in plasma or kidney of SCD mice. We found a significant reduction of proteinuria in SCD mice injected with mildronate compared to SCD mice injected with vehicle. Analysis of H&E-stained kidneys showed significant reduction of glomerular size and medullar congestion areas in the mildronate injected SCD mice. Urinary KIM-1 levels were reduced by mildronate administration. CONCLUSIONS: Our results demonstrate that mildronate ameliorates glomerular and tubular injury in SCD mice and reduces capillary congestion. Mildronate improves renal function, in part by reducing inflammation but not through the reduction of hypoxia or oxidative stress. In future, we plan to assess the mildronate’s impact on kidney function and vessel inflammation. This work was supported by NIH grants R01HL125005, U54MD007597, and SC1HL150685. We thank Xiaomei Niu for helping with the Bio-Plex assay. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Investigation of the effects of p-Coumaric acid on MDA, some antioxidants and histopathological parameters in nephrotoxicity induced by bisphenol A in rats

The aim of this study was to investigate p-Coumaric acid (PCA) as a protector in detecting oxidative and targeted damage in the elongation tissue of rats induced by bisphenol A (BPA). BPA is an environmental pollutant widely used in many areas. The widespread use of this substance increases its transmission to humans. BPA causes damage to many tissues and organs. One of the most frequently damaged organs is the kidney. In this study, fifty healthy male rats were used to determine the effects of BPA and PCA. A total of five experimental groups were formed with ten animals in each group. Group 1 was set as the Control, Group 2 as BPA, Group 3 as BPA+PCA50, Group 4 as BPA+PCA100, and Group 5 as PCA100. The experiment lasted 14 days. Hematoxylin eosin staining and ELISA analyses were performed on kidney tissues at the end of the experiment. Malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and nitric oxide (NO) levels were determined in the kidney tissues by ELISA analysis. It was observed that kidney MDA and NO levels increased in the groups administered BPA while SOD and GSH levels decreased. Histopathologically, degeneration and necrosis in the tubular epithelium, glomerular atrophy, and hyperemia in the vessels were observed in the kidney tissues of the BPA groups. In the BPA+PCA groups it was seen that PCA prevented the negative effects of BPA in a dose-dependent manner, and helped in the maintenance of values close to the control group.

Effects of naringenin on oxidative damage and apoptosis in liver and kidney in rats subjected to chronic mercury chloride.

Mercury chloride is a type of heavy metal that causes the formation of free radicals, causing hepatotoxicity, nephrotoxicity and apoptosis. In this study, the effects of naringenin on oxidative stress and apoptosis in the liver and kidney of rats exposed to mercury chloride were investigated. In the study, 41 2-month-old male Wistar-Albino rats were divided into five groups. Accordingly, group 1 was set as control group, group 2 as naringenin-100, group 3 as mercury chloride, group 4 as mercury chloride + naringenin-50, and group 5 as mercury chloride + naringenin-100. For the interventions, 1 mL/kg saline was administered to the control, 0.4 mg/kg/day mercury (II) chloride to the mercury chloride groups by i.p., and 50 and 100 mg/kg/day naringenin prepared in corn oil to the naringenin groups by gavage. All the interventions lasted for 20 days. Mercury chloride administration was initiated 1 h following the administration of naringenin. When mercury chloride and the control group were compared, a significant increase in plasma urea, liver and kidney malondialdehyde (MDA) levels, in kidney superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) activities (p < .001), and a significant decrease in liver and kidney glutathione (GSH) levels (p < .001), in liver catalase (CAT) activity (p < .01) were observed. In addition, histopathological changes and a significant increase in caspase-3 levels were detected (p < .05). When mercury chloride and treatment groups were compared, the administration of naringenin caused a decrease aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) (p < .01), urea, creatinine levels (p < .001) in plasma, MDA levels in liver and kidney, SOD, GSH-Px, GST activities in kidney (p < .001), and increased GSH levels in liver and kidney. The addition of naringenin-100 increased GSH levels above the control (p < .001). The administration of naringenin was also decreased histopathological changes and caspase-3 levels (p < .05). Accordingly, it was determined that naringenin is protective and therapeutic against mercury chloride-induced oxidative damage and apoptosis in the liver and kidney, and 100 mg/kg naringenin is more effective in preventing histopathological changes and apoptosis.

Evaluation of Effect of Montelukast in the Model of Streptozotocin Induced Diabetic Nephropathy in Rats.

Diabetic nephropathy is a progressive condition and a leading cause of end-stage renal disease. Oxidative stress and inflammation play an important role in its pathogenesis. In pre-clinical studies, Montelukast had shown renoprotective and anti-oxidant properties, hence the study was planned to evaluate the effect of Montelukast in a Streptozotocin (STZ) induced model of diabetic nephropathy. 40 Wistar rats of either sex were randomly divided into four groups viz. 1. Vehicle control group, 2. Enalapril (5 mg/kg), 3. Montelukast low-dose (10 mg/kg) and 4. High-dose (20 mg/kg) group. On day 1, diabetes was induced using a single dose of STZ (60 mg/kg) intraperitoneally. Diabetes induction was verified based on fasting blood glucose (FBG) levels on day 7 and from day 8 to day 42, rats were given study drugs. FBG, serum creatinine, blood urea nitrogen (BUN) and urine microalbumin levels were assessed pre-study and post-study. Assessments of kidney malondialdehyde (MDA), reduced glutathione (GSH) and renal histopathology were carried out at the end of the study. Montelukast 10 mg/kg group showed significantly lower urine microalbumin levels compared to the vehicle control group (p < 0.05). Montelukast 20 mg/kg group showed significantly lower levels of FBG, serum creatinine, BUN and urine microalbumin compared to the vehicle control group (p < 0.05). In addition, Montelukast 20 mg/kg group also showed better effects on kidney MDA and GSH levels (p < 0.05) and histopathological scores compared to the vehicle control group. Montelukast showed a protective effect in the model of diabetic nephropathy because of its antioxidant effect.

Mildronate Ameliorates Kidney Function and Reduces Inflammation in SCD Mice

INTRODUCTION:Sickle cell disease (SCD) is a genetic hemoglobin disorder characterized by hemolytic anemia, vaso-occlusive crisis and inflammation that affects organs such as the kidney, liver, brain, spleen, and heart. SCD is driven by a mutation in the β-globin gene that causes sickling of red blood cells (RBCs). More than 50% of SCD patients are affected by chronic kidney diseases (CKD) and other comorbidities. Vasculopathy is caused by hemolysis-related endothelial dysfunction and inflammation, which collectively contribute to the development of renal disease. Mildronate (also known as Meldonium) is an anti-ischemic and cardio protecting medication approved in Eastern Europe. Mildronate facilitates a switch from fatty acid oxidation to less oxygen-intensive glycolysis that allows less oxygen consumption by peripheral tissues and higher oxygenation of heart. We hypothesized that mildronate administration would reduce tissue hypoxia and decrease inflammation in SCD mice. METHODS: The study was approved by the Institutional Animal Care and Use Committee at Howard University (IACUC). We employed the Townes SCD mouse model, which mimics SCD complications. SCD and control mice were injected with mildronate (400 mg/kg in saline) intraperitoneally or saline as vehicle control over the course of ten days. Blood and plasma were collected and used for hematological parameters analysis. Cytokines were measured by Bio-plex suspension array in plasma and real-time RT-PCR or ELISA in organs. Protein expression of HO-1, HIF-1α, NFκB and NRF2 was measured by Western blot. The effect of Mildronateon systemic and renal oxidative stress was measured by malondialdehyde (MDA) using ELISA (Abcam). RESULTS: We observed significant reduction in the cytokine's levels of IFN-γ, IL-1, and TNF-α in plasma of SCD mice after mildronate injection. We also observed reduction in IL-6, IL-10 and IL-17 levels but differences were not statistically significant. There were no significant changes in hematological parameters (Hematocrit, MCV, MCH, CMCH, Erythrocytes, Hemoglobin) after mildronate injection. Also, we did not observe changes in MDA levels in plasma or kidney in SCD mice compared to control mice, both non-injected and mildronate injected. We further evaluated HO-1 and NRF2 protein expression by western blot and observed no significant differences between SCD mice with or without mildronate injection. In H&amp;E staining, cortex glomerular area and medullar congestion area were significantly reduced after mildronate injection. We also observed reduction of proteinuria in SCD mice injected with mildronate. DISCUSSION: Our examination of the effect of mildronate showed decreases inflammation in the mildronate injected SCD mice evidenced by reduced levels of IFN-γ, IL-1, IL-17, IL-6, IL-10, and TNF-α in circulation. There was a slight decrease in the expression levels of Nrf2 and HO-1 after mildronate injection. HO-1 is crucial for the catabolism of hemoglobin and protects against tissue damage in hemolysis. The HO-1 promoter has binding sites for several transcription factors, including phosphorylated Nrf2. Previous studies from our lab showed increased HIF-1α expression in PBMCs obtained from SCD patients. Here we did not detect significant changes in NFκB-p65 or HIF-1α expression levels. While we expected mildronate to decrease the oxidative stress, we did not observe significant reduction in MDA levels in treated mice compared to control mice. CONCLUSION: Mildronate improved kidney function in SCD mice by reducing circulatory and renal inflammation. In future, we plan to assess in more details the mildronate's impact on kidney function and inflammation. ACKNOWLEDGMENTS: This work was supported by NIH grants 1R01HL125005, 5U54MD007597, and 1SC1HL150685.

Antioxidant Effect of Shallot Peel Infusion on Kidney Oxidative Stress in Diazinon-Induced Wistar Rats

Diazinon is a pesticide widely used by farmers to control pests. Exposure to the low doses of diazinon can occur continuously through a polluted environment and diazinon residues in agricultural products. It has a nephrotoxic effect through oxidative stress mechanism. Flavonoid as antioxidant can significantly neutralize oxidative stress. Shallot peel is a source of flavonoids. This study was designed to determine the antioxidant effect of shallot skin infusion (SPI) on kidney oxidative stress in diazinon-induced Wistar rats by measuring the flavonoid level of SPI and kidney malondialdehyde (MDA) level. Rats were divided into normal, diazinon, and SPI groups. Diazinon was administered at dose of 40 mg/kgBW for 7 days followed by SPI at doses of 500, 1,000, and 2,000 mg/kgBW for 7 days. The flavonoid level of SPI was measured using spectrophotometry method and the kidney MDA level was measured using ELISA method. The flavonoid level of SPI was 96.8 mg QE/L. The results showed that the normal group had the lowest kidney MDA level of 2.585 mM/mL, the diazinon group had the highest level of 2.708 M/mL, while the SPI group at dose of of 500, 1,000, and 2,000 mg/kgBW had renal MDA levels of 2.642 mM/mL, 2.644 mM/mL, and 2.593 mM/mL. Nevertheless, the result of statistical analysis showed that the kidney MDA levels seven days after diazinon administration was not significantly different from the normal group so that SPI administration did not affect the kidney MDA level in diazinon-induced Wistar rats.&#x0D; Keyword: Shallot Peel, Diazinon, Oxidative Stress, Kidney Malondialdehyde

Effect of Salvia officinalis aqueous infusion on copper sulfate-induced inflammatory response and oxidative stress imbalance in mice liver and kidney

Extracts of Salvia officinalis (S. officinalis) have been described to have many therapeutic properties. However, the effect of S. officinalis on copper sulfate toxicity has not been previously reported. The aim of this study was to investigate the toxicity of copper sulfate and the potential beneficial effects of S. officinalis aqueous infusion on proinflammatory response and antioxidant status. 56 male mice were used and equally divided into 6 groups: control group, copper sulfate treated group (40 mg/kg), S. officinalis aqueous infusion treated groups (200 mg/kg and 400 mg/kg) separately or in combination with copper. IL-6 (interleukine-6) and TNF-α (Tumor necrosis factor alpha) were assessed by Elisa. Catalase (CAT), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities, malondialdehyde (MDA) and oxygen peroxide levels were determined. Serum biochemical parameters were analyzed. Copper enhanced aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Lactate dehydrogenase (LDH) (p < 0.05). Copper enhances significantly IL-6, TNF-α and MDA levels in liver and kidney and reduced CAT, SOD and AChE activities (p < 0.05). Aqueous infusion of S. officinalis at 400 mg/kg abolished copper-induced changes in AST and ALT activity. S. officinalis aqueous infusion at 200 mg/kg reversed copper-induced IL-6 in kidney and TNF-α in liver at both doses. S. officinalis aqueous infusion at 400 mg/kg restored SOD in kidney and CAT and AChE activities in both liver and kidney. S. officinalis aqueous infusion may be useful in partially ameliorating tissue disorders induced by copper exposure such as inflammatory response, oxidative stress imbalance and organ dysfunction through its phenolic compounds and higher antioxidant capacity.

The protective impact of glutamine on anti-tuberculosis drug-induced nephrotoxicity in Wistar rats

This study assessed the protective effect of glutamine (GTN) against rifampicin/isoniazid/pyrazinamide/ethambutol (RIPE)-induced nephrotoxicity in rats. Thirty adult Wistar rats (200±20 g) of both sexes were grouped into 6 of 5 rats/group. The rats were treated daily for 30 days as follows: Group 1 (Vehicle control [normal saline 0.2mL]), group 2 (GTN 200 mg/kg), group 3 (RIPE 150, 75, 400 and 275 mg/kg in vehicle), group 4 (GTN 50 mg/kg +RIPE), group 5 (GTN 100 mg/kg +RIPE) and group 6 (GTN 200 mg/kg +RIPE). After treatment, blood samples were obtained and assessed for serum renal biomarkers. Kidneys were harvested, weighed and assessed for oxidative stress markers and histology. RIPE significantly (p&lt;0.01) decreased body weight and significantly (p&lt;0.01) increased kidney weight when compared to the control. Serum urea, creatinine, uric acid levels and kidney malondialdehyde levels were significantly (p&lt;0.001) increased in RIPE-treated rats when compared to the control. Serum total protein, albumin, kidney glutathione, catalase, superoxide dismutase and glutathione peroxidase levels were significantly decreased (p&lt;0.001) in RIPE-treated rats when compared to the control. RIPE caused tubular necrosis and collapsed glomeruli in the kidneys of rats. However, body and liver weights were significantly restored in GTN 100 mg/kg +RIPE and GTN 200 mg/kg +RIPE-treated rats at p&lt;0.05 and p&lt;0.01, respectively when compared to RIPE. Serum and kidney oxidative stress markers were restored in GTN 50 mg/kg +RIPE, GTN 100 mg/kg +RIPE and GTN 200 mg/kg +RIPE-treated rats at p&lt;0.05, p&lt;0.01 and p&lt;0.001 respectively, when compared to RIPE. GTN restored kidney histology. GTN protects against RIPE-induced nephrotoxicity in a dose-related fashion.

Evaluation of renal disturbance in animal models of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine disease characterized by hyperandrogenism and hyperinsulinemia, followed by luteinizing hormone and follicle-stimulating hormone deficiency. PCOS conditions cause metabolic disorders that increase uric acid levels and malondialdehyde (MDA) levels. Animal models of PCOS have been used extensively in research to study the pathogenesis, clinical characteristics, and treatment of PCOS. This study aimed to identify the pathological mechanisms underlying renal dysfunction in PCOS by observing several parameters, including blood urea nitrogen (BUN), creatinine, uric acid, and renal MDA levels. This research was an experimentally designed study using a Wistar rat (Rattus norvegicus) as an animal model of PCOS which were divided into three groups: negative control group (n = 6), Testosterone propionate (TP) induction group (n = 6), and estradiol valerate (EV) induction group (n = 6). According to statistical analysis it indicated that induction of TP and EV can increase blood uric acid levels in PCOS model rats (p < 0.05), TP induction can increase kidney BUN and MDA levels significantly (p < 0.05), However, the observation of creatinine levels did not show significant differences in all treatment groups (p > 0.05). Based on the results of this study, it can be concluded that the induction of animal models with TP can trigger significant renal damage compared to EV.

The Effect of Shallot Peel Ethanol Extract in Reducing Kidney MDA Levels in Diazinon-induced Wistar Rats

Diazinon is an organophosphate pesticide often used by farmer. The residue of diazinon may contaminate agricultural products and if accidentally consumed in a long term, may potentially led to health problems such as kidney disorders. Shallot (Allium cepa) peel was recently proposed to help recover the kidney damage due to its high flavonoid antioxidant content. This study aims to determine the antioxidant effect of shallot peel extract in reducing oxidative stress caused by diazinon with malondialdehyde (MDA) level indicator on the kidney of Wistar rats (Rattus norvegicus). This research was a true experimental with an in-vivo posttest-only control group design. The 28 rats were divided using a simple random sampling technique. The groups were the control group (K0), the diazinon group (K1), SPEE (Shallot Peel Ethanol Extract) groups which are P1 (300 mg/kg BW), P2 (600 mg/kg BW), P3 (900 mg/kg BW), P4 (1200 mg/kg BW) and P5 (2400 mg/kg BW). At the end of the study, the MDA kidney levels was analysed using the TBARS method. Effective doses were found in 600 mg/kg BW/day, 900 mg/kg BW/day, 1200 mg/kg BW/day, and 2400 mg/kg BW/day. The optimal dose of shallot peel extract in this study was 600 mg/kg BW/day. This study showed the effectiveness of shallot peel extract in reducing kidney MDA levels in diazinon-induced Wistar rats.&#x0D; Keywords: shallot peel, diazinon, kidney MDA level

SUPLEMENTASI YOGURT FORTIFIKASI KONSENTRASI BERTINGKAT EKSTRAK ROSELLA UNGU TERHADAP KADAR MALONDIALDEHIDA (MDA) DAN GAMBARAN HISTOLOGI GINJAL MENCIT

Purple roselle has ingredients such as organic acids, anthocyanins, polysaccharides, and flavonoids. The antioxidant content in purple roselle has benefits in preventing cell damage due to free radicals. This study was conducted to discoverthe effect of supplementation yogurt fortified with a graded concentration of purple roselle extract on MDA levels and histology of the kidney organs of mice. Laboratory experimental study using 16 male Balb-C mice divided into four groups. The control (C) group was not given any treatment. The treatment groups 1,2, and 3 (T1, T2, T3) were given fortified purple roselle yogurt with concentrations of 5%, 10%, and 15%, respectively. The treatment was carried out for 14 days with a volume of 0.4 ml/day. Kidney organs were collected for histological analysis. Kidney malondialdehydelevels were assayed using the TBARS test and statistically analyzed with a 95% confidence level by one-way ANOVA analysis. Histology score analyzed using the Kruskal-Wallis test followed by the Mann- Whitney test. This study showedthat at concentrations of 10% and 15%, MDA levels of the mice kidneys reduce significantly compared to the control group. The kidney histology score results show some changes in treatment groups compares to control group. The average score decreasing from different treatment group, and the lowest score was group given yogurt fortified roselle extract 15%. The administration of fortified yogurt with purple roselle extract at a concentration of 15% can reduce MDA levels in the kidneys of mice, and the higher the concentration can reduce kidney damage in mice.

Ameliorating Effect of Malva neglecta Wallr on Obesity and Diabetes in Wistar Rats: A Mechanistic Study.

A high caloric food causes deposition of fats that may progress to obesity. Obesity is a risk factor for various metabolic and cardiovascular diseases, including but limited to diabetes mellitus. This study is aimed at determining the ameliorating effect of Malva Neglecta wallr aqueous-methanolic extract (MNME) on obesity and diabetes in Wistar rats. The MNME was chemically characterized by high-performance liquid chromatography (HPLC). The plant extract was evaluated by in vitro α-amylase inhibition and DPPH scavenging activities. Obesity was induced by administering high sugar and fat diet (HSFD) to rats for six weeks, followed by intraperitoneal injection of alloxan monohydrate (150 mg/kg) to induce diabetes. Oral treatments with MNME 250, 500, and 750 mg/kg/day were given to diabetic obese rats for 14 days. The HPLC analysis showed the presence of phenolic acids and flavonoids. The plant extract showed significant antioxidant (P < 0.001) and alpha-amylase (P < 0.0001) inhibition activities. The administration of MNME displayed a considerable decrease in fasting blood glucose, body weight, liver function tests, urea, cholesterol, leptin, and insulin levels in diabetic obese rats as compared to the disease control group and maximum effect were observed at 750 mg/kg/day of MNME. The MNME significantly increased (P < 0.05 − 0.001) the levels of GSH, SOD, and CAT in the liver, kidney, and pancreas while notably (P < 0.05 − 0.001) reduced the malondialdehyde level in kidney and pancreas of diabetic obese rats in contrast to disease control rats. This experimental study concludes that the MNME had exhibited antiobesity and antidiabetic activities through reduction of oxidative stress, leptin, α-amylase activity, and insulin resistance due to the presence of phenolic acid and flavonoid compounds.

Effects of Ribes khorasanicum hydro-ethanolic extract on streptozotocin-induced diabetic complications in rats.

The anti-diabetic effects of Ribes khorasanicum as a traditional remedy were investigated in diabetic rats. Thirty-five male rats were divided into five groups: control, diabetic, diabetic treated with metformin (300 mg kg-1; D+Met), diabetic treated with 250 and 500 mg kg-1 of Ribes khorasanicum hydro-ethanolic extract (D+Rib250 and D+Rib500). After six weeks of treatment, sera of overnight fasted animals were collected and used for measurement of glucose, insulin, lipid profile, urea, creatinine, and hepatic enzymes levels. Moreover, liver and kidney of rats were removed and used for measurement of oxidative stress including malondialdehyde (MDA), thiol content, and the activity of catalase (CAT) and superoxide dismutase (SOD). Streptozotocin (STZ)-induced diabetes increased the levels of serum glucose, triglycerides (TG), total cholesterol (TC), and LDL-C, urea, creatinine, hepatic enzymes, and kidney and liver oxidative stress markers, while decreased insulin and HDL-C when compared to control group. In all treated groups serum levels of glucose, TC, LDL-C, TG, and urea were decreased, while liver SOD activity was increased compared to the diabetic group. The D+Rib500 group had lower Serum glutamic pyruvic transaminase (SGPT), creatinine, and kidney MDA levels, but higher insulin, HDL-C levels, liver CAT activity, and kidney thiol content, and CAT activity compared to diabetic group. In D+Met group, serum levels of serum glutamic-oxaloacetic transaminase (SGOT), creatinine, and MDA of liver and kidney were decreased, while liver SOD activity was increased compared to the diabetic group. Based on our findings, treatment with Ribes khorasanicum improved diabetic complications, while the effect of a higher dose of the extract was comparable to metformin’s.

Effects of N-acetyl cysteine on TRPM2 expression in kidney and liver tissues following malathion intoxication

ABSTRACT We investigated the effects of N-acetyl cysteine (NAC) on transient receptor potential melastatin 2 (TRPM2) channel expression in rat kidney and liver tissues following experimental malathion intoxication. We used seven groups of six male Wistar albino rats: control group, NAC, pralidoxime + atropine, malathion, malathion + pralidoxime + atropine, malathion + pralidoxime + atropine + NAC, and malathion + NAC. Single doses of 100 mg/kg N-acetyl cysteine, 40 mg/kg pralidoxime, 2 mg/kg atropine and 1/3 the lethal dose of malathion were administered. No difference in malondialdehyde (MDA) levels, apoptosis or TRPM2 immunoreactivity was found in liver tissue among the groups. In kidney tissue, MDA levels, apoptosis and TRPM2 immunoreactivity were increased significantly in the malathion and malathion + NAC groups compared to the control group. We found that organophosphate intoxication did not affect MDA, apoptosis or TRPM2 immunoreactivity in rat liver during the acute period. By contrast, we found that in kidney tissue, MDA, apoptosis, and TRPM2 immunoreactivity were increased significantly following administration of malathion. Also, NAC given in addition to pralidoxime and atropine reduced MDA to control levels.

Pullu sazan (Cyprinus carpio Linneaus, 1758)’da ellajik asidin büyüme ve bazı antioksidan parametrelere etkisi

In the present study, it was investigated the effects of various levels of dietary ellagic acid on growth performance and antioxidant status in scaly carp (Cyprinus carpio). Fish were fed with the control diet and three different experimental diets containing three graded levels of ellagic acid (50, 100 and 200 mg kg-1 diet) for 60 days. On 30th and 60th days of experiment, the growth performance [live weight gain, relative growth and specific growth rate] and oxidant/antioxidant parameters [malondialdehyde level, catalase and glutathione-S-transferase activities and reduced glutathione level] were analysed. There was no statistically significant difference in the live weight gain, relative growth and specific growth rates of the control and ellagic acid treated groups (p &gt; 0.05). When compared to the control group, the liver and kidney malondialdehyde levels of ellagic acid treated groups were significantly decreased (p &lt; 0.05). The liver and kidney catalase and glutathione-S-transferase activities and reduced glutathione levels of ellagic acid treated groups were significantly increased when compared to the control group (p &lt; 0.05). It was concluded that ellagic acid can be used as an antioxidant in fish.

Curcumin prevents tenofovir/lamivudine/efavirenzinduced nephrotoxicity in rats

Background and Aims: Nephrotoxicity is an adverse effect, which may occur with the use of tenofovir/lamivudine/efavirenz (TLE) in the treatment of human immune deficiency virus (HIV) infection. Curcumin (CUM), an isolate of Curcuma longa L. is used in folk medicine for the treatment of ailments. This study attempts to establish whether CUM supplementation can protect against a rat model of TLE-induced nephrotoxicity. Materials and Methods: Adult male Wistar rats (n=40) were randomly grouped and supplemented orally with CUM (50, 100 and 200 mg/kg/day) prior to the oral administration of TLE (300/300/600 mg/kg/day) for 30 days. After the treatment, the rats were fasted overnight, weighed and anesthetized. Blood samples were collected, and sera were extracted for biochemical analyses. Kidney samples were excised, weighed and processed for oxidative stress markers and histology. Results: Body weight was decreased (p&lt;0.01) whereas kidney weight was increased (p&lt;0.01) in TLE administered rats when compared to the control. Significant (p&lt;0.001) increments in serum uric acid, creatinine, urea and kidney malondialdehyde levels were observed in TLE-administered rats. Significant (p&lt;0.001) decreases in serum total protein, albumin, electrolytes, kidney superoxide dismutase, glutathione, catalase and glutathione peroxidase levels were observed in TLE administered rats when compared to the control. TLE produced tubular necrosis and hypercellular glomerulus with mesangial proliferation in the kidneys of treated rats. However, CUM (50, 100 and 200 mg/kg) supplementation abrogates TLE-induced nephrotoxicity in a dose-related manner at p&lt;0.05, p&lt;0.01 and p&lt;0.001, respectively, when compared to TLE group. Conclusion: CUM seems effective against TLE-induced nephrotoxicity.

The protective effect of metformin and exenatide on doxorubicin-induced nephrotoxicity in rats

Objective The aim was to study the protective effect of metformin and exenatide on doxorubicin (DOX)-induced nephrotoxicity in rats. Background DOX is an effective chemotherapeutic agent used for treatment of various solid as well as hematological neoplasms. Its use is limited owing to well-documented nephrotoxicity. Treatment with metformin and exenatide ameliorates nephrotoxicity in rats through antioxidant and antiapoptotic effects. Materials and methods In this experimental study, rats were divided as follows: group 1 was injected with saline intraperitoneal and orally, group 2 was injected with intraperitoneal DOX (15 mg/kg) and oral saline, group 3 was injected with intraperitoneal DOX and received metformin (250 mg/kg/day) orally, group 4 was injected with intraperitoneal DOX and received exenatide (10 μg/kg twice daily) Sc, and group 5 was injected with intraperitoneal DOX and metformin + exenatide. Basal body weight (Wt.), final body Wt., kidney Wt., kidney index, kidney malondialdehyde (MDA), reduced glutathione (GSH), serum tumor necrosis factor-α (TNF-α), serum albumin, serum urea and creatinine, urinary proteins, histopathological examination of hematoxylin and eosin, and caspase-3 immunostaining were evaluated. Results DOX group showed a significant decrease in body Wt, GSH levels, and serum albumin, with an increase in kidney Wt., kidney index, serum TNF-α, kidney MDA levels, urine proteins, serum urea and creatinine, and caspase-3 immunoexpression compared with the control group. In contrast, metformin-, exenatide-, and metformin + exenatide-treated groups showed significant increase in body Wt. and kidney GSH levels, with a decrease in kidney Wt., serum TNF-α, kidney MDA levels, and caspase-3 immunoexpression compared with DOX group. Conclusion Metformin and exenatide improved DOX nephrotoxicity in rats.

Clitoria ternatea L. extract prevents kidney damage by suppressing the Ang II/Nox4/oxidative stress cascade in l-NAME-induced hypertension model of rats

Clitoria ternatia L. (CT) has been reported to have anti-inflammatory and antioxidant effects. This study investigated the effect of CT aqueous flower extract on blood pressure and renal alterations in Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME)-induced hypertensive rats. Male Sprague Dawley rats received l-NAME in drinking water and were treated with CT flower extract or lisinopril. CT aqueous flower extract and lisinopril alleviated l-NAME-induced hypertension (p < 0.05). Glomerular extracellular matrix accumulation, renal fibrosis, and increased serum creatinine levels were observed in l-NAME-induced hypertensive rats and attenuated by CT flower extract or lisinopril co-treatment (p < 0.05). High levels of plasma angiotensin II (Ang II) and upregulated nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) protein expression in the kidneys induced by l-NAME were alleviated by CT flower extract or lisinopril co-treatment (p < 0.05). Furthermore, CT flower extract and lisinopril treatment reduced lipid peroxidation and elevated plasma and kidney malondialdehyde levels in l-NAME-induced hypertensive rats (p < 0.05). In conclusion, CT flower extract prevented l-NAME-induced renal injury and dysfunction in rats. The possible mechanism may be related to the suppression of Ang II-mediated Nox4 expression and the oxidative stress cascade in rats.

MO629XANTHINE OXIDASE INHIBITOR ATTENUATES RENAL OXIDATIVE STRESS AND ENDOTHELIAL DYSFUNCTION THROUGH THE INHIBITION OF VEGF-NADPH OXIDASES IN DIABETIC NEPHROPATHY

Abstract Background and Aims Xanthine oxidase (XO) is one of major source of reactive oxygen species, and a XO inhibitor, febuxostat has been reported to the protection of kidney diseases. We investigated whether febuxostat exerts renoprotective effects against diabetic nephropathy (DN). Method Eight-week Male C57BL/6 mice were divided into four groups: Control group (Cont), Febuxostat control group (FEB), streptozotocin treated group (STZ) and a febuxostat and STZ-treated diabetes group (STZ+FEB). STZ was used to induce diabetes (50 mg/kg/day, 5 days), and 5 mg/kg of febuxostat was treated to experimental mice for 8 weeks. Results STZ-treated diabetic mice were significantly decreased in serum and kidney XO levels, serum cystatin C and albuminuria by febuxostat treatment. Febuxostat treatment decreased renal hypertrophy and mesangial matrix expansion in STZ-treated diabetic mice. Febuxostat treatment suppressed the expression of vascular endothelial growth factor (VEGF)1 and 3, NADPH oxidase (NOX)1, 2, and 4, and the levels of their catalytic subunit mRNA in in STZ-treated diabetic mice. Febuxostat treatment was accompanied by the downregulation of Akt phosphorylation, followed by the suppression of transcription factor forkhead box O3a phosphorylation and the enhancement of endothelial nitric oxide synthase. Finally, febuxostat improved oxidative stress and resulted in decreased 8-hydroxy-2'-deoxyguanosine and kidney malondialdehyde levels, and increased superoxide dismutase activity in STZ-treated diabetic mice. Conclusions Febuxostat attenuated DN by modulating oxidative stress and endothelial function through VEGF–NADPH oxidase signaling pathway.

Flacourtia indica fruit extract modulated antioxidant gene expression, prevented oxidative stress and ameliorated kidney dysfunction in isoprenaline administered rats

This study evaluated the effect of Flacourtia indica fruit extract against isoprenaline (ISO) induced renal damage in rats. This investigation showed that ISO administration in rats increased the level oxidative stress biomarkers such as malondialdehyde (MDA), nitric oxide (NO), advanced protein oxidation product (APOP) in kidneys followed by a decrease in antioxidant enzymes functions. Flacourtia indica fruit extract, which is rich in strong antioxidants, also reduced the MDA, NO and APOP level in kidney of ISO administered rats. Inflammation and necrosis was also visible in kidney section of ISO administered rats which was significantly prevented by atenolol and Flacourtia indica fruit extract. Moreover, atenolol and Flacourtia indica fruit extract also modulated the genes expressions related to inflammation and oxidative stress in kidneys. The beneficial effects could be attributed to the presence of a number of phenolic antioxidants. This study suggests that Flacourtia indica fruit extract may prevent kidney dysfunction in ISO administered rats, probably by preventing oxidative stress and inflammation.