Renal Tissue Superoxide Dismutase Research Articles

Neferine inhibits the progression of diabetic nephropathy by modulating the miR-17-5p/nuclear factor E2-related factor 2 axis.

To investigate the effect of Neferine (Nef) on diabetic nephropathy (DN) and to explore the mechanism of Nef in DN based on miRNA regulation theory. A DN mouse model was constructed and treated with Nef. Serum creatinine (Crea), blood urea (UREA) and urinary albumin were measured in mice by kits, and renal histopathological changes and fibrosis were observed by hematoxylin-eosin staining and Masson staining. Renal tissue superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) activities were measured by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the expression of nuclear factor E2-related factor 2 (Nrf2)/ heme oxygenase 1 (HO-1) signaling pathway-related proteins in kidney tissues. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-17-5p in kidney tissues. Subsequently, a DN in vitro model was constructed by high glucose culture of human mesangial cells (HMCs), cells were transfected with miR-17-5p mimic and/or treated with Nef, and we used qRT-PCR to detect cellular miR-17 expression, flow cytometry to detect apoptosis, ELISAs to detect cellular SOD, MDA, and GSH-Px activities, Western blots to detect Nrf2/HO-1 signaling pathway-related protein expression, and dual luciferase reporter gene assays to verify the targeting relationship between Nrf2 and miR-17-5p. Administration of Nef significantly reduced the levels of blood glucose, Crea, and UREA and the expression of miR-17-5p, improved renal histopathology and fibrosis, significantly reduced MDA levels, elevated SOD and GSH-Px activities, and activated Nrf2 expression in kidney tissues from mice with DN. Nrf2 is a post-transcriptional target of miR-17-5p. In HMCs transfected with miR-17-5p mimics, the mRNA and protein levels of Nrf2 were significantly suppressed. Furthermore, miR-17-5p overexpression and Nef intervention resulted in a significant increase in high glucose-induced apoptosis and MDA levels in HMCs and a significant decrease in the protein expression of HO-1 and Nrf2. Collectively, these results indicate that Nef has an ameliorative effect on DN, and the mechanism may be through the miR-17-5p/Nrf2 pathway.

Nephroprotective effects of Candesartan Cilexetil against Cyclosporine A-induced nephrotoxicity in a rat model.

Cyclosporine A (CsA), a well-known immunosuppressive drug, has been prescribed after organ transplantation and in a variety of disorders with an immunological origin. Nephrotoxicity is one of the most frequently stated problems associated with CsA, and therefore the treatment with CsA remains a big challenge. This study sets out to assess the ameliorative influences of Candesartan Cilexetil (CC) on oxidative stress and the nephrotoxic effect of CsA in a rat model. Twenty-four Wister Albino rats, 7-8-week-old, weighing 150-250g, were randomly categorized into three groups (eight animals in each group). These groups were the (1) CsA-treated group, (2) vehicle-treated group, and (3) CC-treated group. Bodyweights were assessed at the start and end of experiments. Renal function test and levels of glutathione peroxidase 1 catalase -CAT (Gpx1), catalase (CAT), superoxide dismutase (SOD), interleukin -2 (IL-2), and malondialdehyde (MDA) were investigated in renal tissues. Histological changes in kidneys were also evaluated. Data showed that levels of urea and creatinine in serum and levels of IL-2 and MDA in renal tissues were elevated in the CsA-treated group, with severe histological changes compared with the control group. Furthermore, tissue levels of Gpx1, CAT, and SOD were significantly decreased in CsA-treated in comparison with the control group. Treatment with CC for the rats subjected to CSA resulted in a marked reduction in levels of serum urea and creatinine and tissue levels of IL-2 and MDA. Levels of Gpx1, CAT, and SOD in renal tissues were greater in the CC-treatment group compared with the CsA-treated group. CC treatment reduced the deterioration of renal morphology compared with CsA treatment. The findings of this study suggest that CC could prevent CSA-induced nephrotoxicity through its anti-inflammatory and antioxidant influences. Considerably more work needs to be done to determine the mechanistic insight behind the ameliorative effect of CC.

Qingda granule alleviate angiotensin ⅱ-induced hypertensive renal injury by suppressing oxidative stress and inflammation through NOX1 and NF-κB pathways

Hypertension has become one of the important diseases harmful to human health. In China, Qingda granule (QDG) has been used to treat hypertension for decades. Previous studies by our team have shown that oxidative stress may be one of the pathways through which QDG inhibits hypertension-induced organs injury. However, the specific molecular mechanism of its anti-hypotension and renal oxidative stress response were unclearly. This study investigated QDG’s potential protective mechanism against hypertension-induced renal injury. Mice were infused with Angiotensin Ⅱ (Ang Ⅱ, 500 ng/kg/min) or equivalent saline solution (Control) and administered oral QDG (1.145 g/kg/day) or saline for four weeks. QDG treatment mitigated the elevated blood pressure and reduced renal pathological changes induced by Ang Ⅱ. As per the RNA sequencing results, QDG affects oxidative stress signaling. In agreement with these findings, QDG significantly attenuated the Ang Ⅱ-induced increase in Nitrogen oxides 1 (NOX1) and reactive oxygen species and the decrease in superoxide dismutase in renal tissue. Additionally, QDG significantly inhibited Interleukin 6 (IL-6), Tumor necrosis factor α (TNF-α), and Interleukin 1β (IL-1β) expression in renal tissues and blocked the phosphorylation of P65 (NF-κB subunit) and IκB. These results were confirmed in vitro. Overall, QDG reduced Ang Ⅱ-induced elevated blood pressure and renal injury by inhibiting oxidative stress and inflammation caused by NOX1 and NF-κB pathways. The results of this study provide an experimental basis for the clinical application of QDG, and to open up a new direction for the clinical treatment of hypertension.

Modulatory role of garlic ( Allium sativum) extract against cisplatin- induced nephrotoxicity in female albino rats and their offspring.

Background: Cisplatin (CP) is one of the chemotherapeutic drugs widely utilized in the treatment of several malignancies. However, recently; its use has been limited because of its hazardous health drawbacks. Previous researches confirmed that CP has severe deleterious side effects on pregnant mothers and their fetuses. Garlic ( Allium sativum) extract has been claimed to exhibit potent antioxidative and free radical scavenging abilities. Aim: This work is mainly designed to evaluate the potential therapeutic role of garlic extract against CP-induced nephrotoxicity in pregnant rats and their offspring. Methods: 24 pregnant rats were used in the current study. They were randomly allocated into four groups (n=6): control, garlic, CP, and CP + garlic group. At the end of the weaning period, the mothers and the offsprings of all groups were sacrificed, the kidneys were immediately excised, and processed for histological and biochemical investigations. Also, blood samples were withdrawn and processed for estimation of the assigned biochemical parameters. Results: The renal histological sections from CP-treated mother rats displayed pronounced histopathological lesions however, their offspring showed mild renal histopathological lesions if compared with those of their mothers. The levels of renal tissue Superoxide dismutase, catalase, and glutathione peroxidase enzymes were significantly decreased. On the contrary, the levels of malondialdehyde, serum urea, and creatinine were significantly increased in CP-treated mother rats and their offspring as compared with control. The percentage value of caspase 3 activity was markedly elevated in the renal tissues of CP-treated mother rats and their offspring compared to the control group. Supplementation of garlic extract to the CP treated rats; the overall histological lesions, as well as biochemical parameters, were restored nearly to the control ones. It is concluded that garlic ( Allium sativum) extract has a powerful ameliorative role against CP-induced nephrotoxicity in pregnant rats and their offspring.

Extraction of lycopene from tomato pomace and its protective effects on renal injury in diabetic rats

The aim of this study was to investigate the protective effects of lycopene from tomato pomace on renal injury in diabetic rats. Lycopene was extracted from tomato pomace. The rats were divided into control, model and 10, 20 and mg/kg lycopene groups. The diabetic nephropathy model was constructed in the latter four groups. Then, the latter three groups were treated with 10, 20 and mg/kg lycopene, respectively. After four weeks of treatment, compared with the model group, in 20 and 40 mg/kg lycopene groups the serum fasting plasma glucose level was decreased (P < 0.05), the fasting insulin level was increased (P < 0.05), the renal index and 24-h urinary protein level were decreased (P < 0.05), the blood urea nitrogen and serum creatinine levels were decreased (P < 0.05), the renal tissue superoxide dismutase and glutathione peroxidase levels were increased (P < 0.05), the renal tissue malondialdehyde level was decreased (P < 0.05), and the serum tumor necrosis factor α, interleukin 6 and hypersensitive C-reactive protein levels were decreased (P < 0.05). In conclusion, lycopene from tomato pomace can alleviate renal injury in diabetic rats. The mechanism may be related to the resistance of oxidative stress and inflammatory response.

Chrysin attenuates sodium arsenite-induced nephrotoxicity in rats by suppressing oxidative stress and inflammation

BackgroundWe aimed to study the beneficial property of chrysin (CHR) by targeting its antioxidant and anti-inflammatory effects on nephrotoxicity induced by sodium arsenite (SA). Materials & methodsWe have used the 35 male Wistar rats in five equal groups (n = 7). Normal saline in (5 ml/kg; p.o.; 21 days) was given to the control group. Sodium arsenite (10 mg/kg; p.o.; 14 days) was given to the SA group. CHR (25, 50 and 100 mg/kg; p.o.; 21 days) and SA (10 mg/kg; p.o.; 14 days from the 7th day of the experiment) was given to the SA + CHR 25, 50 and 100 groups. On the 22nd day of the experiment, the animals’ bloods and kidneys were taken, and then we have performed functional, biochemical and histological assessment. ResultsCHR pre- and alongside administration (more potently at dose of 100 mg/kg) with SA reduced the SA-induced alterations in serum creatinine and blood urine nitrogen levels. Increased levels of protein carbonyl, myeloperoxidase, malondialdehyde and nitric oxide in kidney tissue were decreased by CHR treatment. CHR administration increased the levels of glutathione and activities of glutathione peroxidase, catalase and superoxide dismutase in renal tissue. Moreover, treatment with CHR reduced the levels of inflammatory mediators including interleukin 1 beta and tumor necrosis factor alpha in renal tissue. The renal histological lesions induced SA were mitigated by CHR treatment in dose dependent manner. ConclusionThe results of present study suggested that administration of CHR before and alongside with SA attenuated the renal toxic effects of SA via antioxidative stress and anti-inflammatory effects.

Nicorandil mitigates folic acid-induced nephrotoxicity in mice: Role of iNOS and eNOS.

Folic acid (FA)-induced acute kidney injury (AKI) is a commonly used model in experimental animals for studying renal injury. This study aimed to investigate the probable protecting impact of nicorandil against FA-induced renal dysfunction. A mouse model was executed by a single injection of FA (250 mg/kg). Nicorandil was orally administrated in two doses (50 and 100 mg/kg) for 10 days. Nicorandil repressed the progression of FA-induced AKI as evidenced by the improvement of histopathological alterations and the substantial decrease of serum levels of creatinine, urea, blood urea nitrogen, malondialdehyde (MDA), and urinary protein levels. Moreover, nicorandil resulted in a profound reduction in oxidative stress as manifested by decreased MDA and increased reduced glutathioneand superoxide dismutasein renal tissue. Notably, nicorandil suppressed FA-induced inflammation; it reduced renal levels of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, nicorandil decreased renal levels of nitric oxide, inducible nitric oxide synthase, and increased endothelial nitric oxide synthase. Lastly, nicorandil efficiently decreased expression of the proapoptotic protein (Bax) and caspase 3. Nicorandil confers dose-dependent protection against FA-induced AKI by alleviating oxidative stress, inflammation besides modulating nitric oxide synthaseand reducing apoptosis.

Effect of dexmedetomidine on ischemia-reperfusion injury of liver and kidney tissues in experimental diabetes and hepatic ischemia-reperfusion injury induced rats

Background: Reperfusion following ischemia can lead to more injuries than ischemia itself especially in diabetic patients. The aim of this study was to evaluate the effect of dexmedetomidine on ischemia-reperfusion injury (IRI) in rats with have hepatic IRI and diabetes mellitus.

An experimental study of exenatide effects on renal injury in diabetic rats1.

Purpose To investigate the effects of exenatide on renal injury in streptozotocin-induced diabetic rats. Methods Fifty SD rats were randomly divided into normal control, model, exenatide-1, exenatide-2 and exenatide-3 groups, 10 rats in each group. The diabetic nephropathy model was constructed in later 4 groups. Then, the later 3 groups were treated with 2, 4 and 8 μg/kg exenatide for 8 weeks, respectively. The serum and urine biochemical indexes and oxidative stress and inflammatory indexes in renal tissue were determined. ResultsCompared to the model group, in exenatide-3 group the serum fasting plasma glucose and hemoglobin A1c levels were significantly decreased, the fasting insulin level was significantly increased, the renal index and blood urea nitrogen, serum creatinine and 24 h urine protein levels were significantly decreased, the renal tissue superoxide dismutase and glutathione peroxidase levels were significantly increased, the malondialdehyde level was significantly decreased, and the renal tissue tumor necrosis factor alpha, interleukin 6, hypersensitive C-reactive protein and chemokine (C-C motif) ligand 5 levels were significantly decreased P<0.05). ConclusionsExenatide can mitigate the renal injury in diabetic rats. The mechanisms may be related to its resistance of oxidative stress and inflammatory response in renal tissue.

Gypenoside attenuates renal ischemia/reperfusion injury in mice by inhibition of ERK signaling.

Gynostemma pentaphyllum is a traditional Chinese medicine reported to possess a wide range of health benefits. As the major component of G. pentaphyllum, gypenoside (GP) displays various anti-inflammatory and anti-oxidant properties. However, it is unclear whether GP can protect against ischemia/reperfusion (I/R)-induced renal injury, and the underlying molecular mechanisms associated with this process remain unknown. In the present study, a renal I/R injury model in C57BL/6 mice was established. It was observed that, following I/R, serum concentrations of creatinine (Cr) and blood urea nitrogen (BUN) were significantly increased (P<0.01), indicating renal injury. Pretreatment with GP (50 mg/kg) significantly inhibited I/R-induced upregulation of serum Cr and BUN (P<0.01). Furthermore, renal malondialdehyde levels were significantly reduced in the I/R+GP group, compared with the I/R group (P<0.01), whereas renal tissue superoxide dismutase activity was significantly higher in the I/R+GP group compared with the I/R group (P<0.01). Further investigation demonstrated that pretreatment with GP produced inhibitory effects on the I/R-induced production of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α and interferon-γ (P<0.01). In addition, heme oxygenase 1 (HO-1) expression levels were significantly increased in the I/R group compared with the control (P<0.01), indicating the presence of oxidative damage. However, the I/R-induced upregulation of HO-1 was significantly attenuated by pretreatment with GP (P<0.01), which also suppressed I/R-induced apoptosis by inhibiting pro-apoptotic Bax and upregulating anti-apoptotic Bcl-2 in renal cells (P<0.01). Finally, the activity of ERK signaling was significantly increased in the I/R+GP group compared with the I/R group (P<0.05), which may be associated with the protective effect of GP against I/R-induced renal cell apoptosis. To conclude, the present results suggest that GP produces a protective effect against I/R-induced renal injury as a result of its anti-inflammatory and anti-apoptotic properties.

Betaine supplementation mitigates cisplatin-induced nephrotoxicity by abrogation of oxidative/nitrosative stress and suppression of inflammation and apoptosis in rats

Cisplatin is one of the most potent chemotherapeutic antitumor drugs used in the treatment of a wide range of solid tumors. Its primary dose-limiting side effect is nephrotoxicity. This study aims to investigate the effect of betaine supplementation on cisplatin-induced nephrotoxicity. A single intraperitoneal injection of cisplatin (5mg/kg) deteriorated the kidney functions as reflected by elevated blood urea nitrogen and serum creatinine levels. Oxidative/nitrosative stress was evident in cisplatin group by increased renal thiobarbituric acid-reactive substances (TBARS), an indicator of lipid peroxidation, reduced renal total antioxidant status and increased renal nitrite concentration. Cisplatin resulted in a decline in the concentrations of reduced glutathione, glutathione peroxidase, catalase, and superoxide dismutase in renal tissues. Renal tumor necrosis factor-α (TNF-α) was also elevated. Expressions of nuclear factor-kappa B (NF-κB) and caspase-3 were up-regulated in renal tissues as indicated by immunohistochemical analysis. Histopathological changes were observed in cisplatin group. Betaine supplementation (250mg/kg/day) orally via gavage for 21 days prior to cisplatin injection was able to protect against deterioration in kidney function, abrogate the decline in antioxidants enzymes and suppressed the increase in TBARS, nitrite and TNF-α concentrations. Moreover, betaine inhibited NF-κB and caspase-3 activation and improved the histological changes induced by cisplatin. Thus, the present study demonstrated the renoprotective nature of betaine by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant competence in kidney tissues of cisplatin treated rats. Betaine could be a beneficial dietary supplement to attenuate cisplatin nephrotoxicity.

Prophylactic effects of quercetin and hyperoside in a calcium oxalate stone forming rat model.

Quercetin and hyperoside (QH) are the two main constituents of the total flavone glycosides of Flos Abelmoschus manihot, which has been prescribed for treating chronic kidney disease for decades. This study aimed to investigate the effect of QH on calcium oxalate (CaOx) formation in ethylene glycol (EG)-fed rats. Rats were divided into three groups: an untreated stone-forming group, a QH-treated stone-forming group (20 mg/kg/day) and a potassium citrate-treated stone-forming group (potassium citrate was a worldwide-recognized calculi-prophylactic medicine). Ethylene glycol (0.5 %) was administered to the rats during the last week, and vitamin D3 was force-fed to induce hyperoxaluria and kidney calcium oxalate crystal deposition. 24 h urine samples were collected before and after inducing crystal deposits. Rats were killed and both kidneys were harvested after 3 weeks. Bisected kidneys were examined under a polarized light microscope for semi-quantification of the crystal-formation. The renal tissue superoxide dismutase and catalase levels were measured by Western blot. QH and potassium citrate have the ability to alkalinize urine. The number of crystal deposits decreased significantly in the QH-treated stone-forming group as compared to the other groups. Superoxide dismutase and catalase levels also increased significantly in the QH-treated stone-forming group, as compared with the untreated stone-forming group. QH administration has an inhibitory effect on the deposition of CaOx crystal in EG-fed rats and may be effective for preventing stone-forming disease.

Renoprotective effect of sitagliptin against hypertensive nephropathy induced by chronic administration of L-NAME in rats: Role of GLP-1 and GLP-1 receptor

The present study was undertaken to assess the possible protective effects of sitagliptin, a dipeptidyl peptidase 4-inhibitor (DPP4), against Nω-nitro-L-arginine methyl ester (L-NAME) induced hypertensive nephropathy in rats. Hypertension was induced in adult rats by administration of L-NAME for 6 weeks. Rats were treated with sitagliptin (10mg/kg/day or 30mg/kg/day) for six weeks. Chronic L-NAME administration resulted in depletion of serum nitric oxide (NO) associated with elevation in the mean arterial pressure. When compared with the control group; serum urea, serum creatinine, albuminuria, urinary N-acetyl-ß-d-glucosaminidase (NAG) level and renal tissue malondialdhyde (MDA) content were significantly elevated, while creatinine clearance, serum level of glucagon like peptide-1 (GLP-1) as well as renal tissue superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were signifcantly decreased in L-NAME treated group. Renal expression of mRNA for eNOS and GLP-1 receptors were reduced in the L-NAME treated group as compared with the control group. Treatment with sitagliptin (10mg/kg or 30mg/kg) successfully ameliorated the deleterious effects of L-NAME on the all tested parameters. Our study indicates a novel protective effect of sitagliptin against L-NAME induced hypertensive nephropathy. An effect which is mediated through, increasing serum level of GLP-1, upregulation of GLP-1 receptors, which in turn, lead to induction of expression eNOS, increased serum NO level, tandem with decreased lipid perodixation and restore the antioxidant defense mechanisms. It is worth mentioning that the effects produced by sitaglipin (30mg/kg) were superior to the effects obtained by the lower dose.

Effect of subchronic inhalation of ethylbenzene on expression of heme oxygenase-1 in rat renal tissues

To investigate the effect of ethylbenzene on the expression of heme oxygenase-1 (HO-1) intrarenal tissues. Forty male Sprague-Dawley rats were randomly and equally allocated to control group, low-dose exposure group, moderate-dose exposure group, and high-dose exposure group to inhale different doses of ethylbenzene (0, 433.5 mg/m(3) (100 ppm), 4335.0 mg/m(3) (1000 ppm), and 6500.0 mg/m(3) (1500 ppm)) for 6 h per day, 5 days per week, for 13 weeks. After the rat model of subchronic ethylbenzene exposure was established, the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) in renal tissues were measured, and the mRNA and protein expression levels of HO-1 in renal tissues were measured by real-time PCR and Western blot. Compared with the control group, all exposure groups showed significantly decreased activities of GSH-Px and CAT in renal tissues and the moderate- and high-dose exposure groups showed significantly decreased activity of SOD in renal tissues (P < 0.05). All exposure groups showed significantly higher expression of HO-1 than the control group (P < 0.05). The high-dose exposure group showed significantly higher expression of HO-1 than the low- and moderate-dose exposure group (P < 0.05), and the moderate- and high-dose exposure group had significantly higher expression of HO-1 than the control group and low-dose exposure group (P < 0.05). A certain dose of ethylbenzene can induce elevated expression of HO-1 and decreased antioxidant levels in rat renal tissues, thus leading to oxidative stress damage.

Efficiency of Endovenous Versus Arterial Administration of Mesenchymal Stem Cells for Ischemia-Reperfusion–Induced Renal Dysfunction in Rats

BackgroundIschemia followed by reperfusion leads to acute renal failure in both native kidneys and a renal allograft. Our previous study found that transplantation of mesenchymal stem cells (MSCs) ameliorated ischemia-reperfusion (I/R)-induced kidney dysfunction by increasing the activities of antioxidant enzymes. The purpose of this study was to evaluate whether intra-arterial versus intravenous administration was more effective. MethodsRenal ischemia was induced by clamping the right renal vessels for 60 minutes after removal of the left kidney. MSCs (1 × 106) were administered through either the tail vein (TV) or the renal arter (RA), followed by reperfusion. We evaluated kidney function as well as tissue activities of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Histopathologic and immunohistochemical examinations were performed. To tracking MSCs in vivo, they were transfected with firefly luciferase and monomeric red fluorescent protein reporter genes (fluc-mrfp). MSC retention and survival were assessed using bioluminescence imaging. We observed the effects of MSCs (1 × 106, 2 × 106, and 5 × 106) on IR injury. ResultsMSC infusion via either the tail vein or the renal artery significantly improved kidney function at days 1, 3, and 5 as indicated by lower urea and creatinine levels compared with vehicle controls (P < .05). I/R induced a reduction in renal tissue SOD activity but GSH-PX was significantly improved by MSCs (P < .05) on day 1. Treatment with MSCs also significantly reduced renal tissue MDA levels that had been otherwise increased by renal I/R injury (P < .05). The above parameters were similar between the TV and the RA groups. Histological examination revealed kidneys from MSC-treated rats to show fairly normal morphology. The percentages of proliferating cell nuclear antigen (PCNA)-positive cells were higher in the MSC groups: 16.83 ± 4.62%, 19.17 ± 6.21%, and 2.17 ± 1.16% for the TV, RA, and control groups, respectively. There was no significant dose-related difference among MSC groups. Bioluminescence imaging demonstrated most MSCs to be lost within 7 days after either intravenous or intra-arterial infusion. ConclusionsMSCs ameliorated I/R-induced acute renal failure in rats with similar efficiency whether infused either through the TV or the RA. There was no dose-dependent responses.

Establishment of the models of cold ischemia and reperfusion injury in rat kidney

Objective In this study,for studying IRI in kidney transplantation. ,we established the models of cold ischemia and reperfusion injury in rats. Methods Twenty four SD rats were randomly assigned to two groups:control (A) ,and experimental (B) group. Group A was only removed the right kidney. Cold ischemia reperfusion was performed as the follow-listed model in Group B. The main process of the model: ( 1) Perfusing left kidney: after resected the right kidney of the rat, one pipe was put in the remainder right renal artery to perfuse the left kidney. The perfusion flowed out through another pipe in the right renal vein. The blood vessels of left kidney were clipped after cold perfusion. (2) Cold ischemic conservancy : the operation table was leant to left side, and the left kidney was taken out of abdominal cavity then stored in a cold bag which was full of ice and water,but the vessels of that were intact. (3) Reperfusing left kidney: after 60 minutes, the clip was removed. Left kidneys of all rats in two groups were removed to be detected. Structure of the kidney was evaluated by light microscopy and electronic microscopy. Superoxide dismutase ( SOD) activity and malondialdehyde ( MDA) content in the renal tissues was examined,and the renal function was also assessed by determining the levels of blood urea nitrogen ( BUN) and serum creatinine (CR) before and 24 hours after operation. Results (1) Morphologic change (hematoxylin-eosin staining) :A normal morphology was observed by light microscopy and electon microscopy in group A.Significant injury was detected in group B. (2 ) In group A, there was not significant difference about BUN and CR between before and after operation (P ＞0. 05) ,but in Group B,those increased significantly at 24 hour after operation (P ＜0. 05). (3) Activity of SOD in renal tissues in group A was higher than those in group B (P ＜ 0. 05 ) , meanwhile, Content of MDA in group A was lower than those in group B ( P ＜0. 05 ).Conclusion The rat renal cold ischemia reperfusion model we established is feasible regardless of experimental conditions, and can be studied as the events following IRI in kidney transplantation. Key words: Kidney; Cold; Ischemia; Reperfusion injury

Lisinopril attenuates renal oxidative injury in l-NAME-induced hypertensive rats

Hypertension and related oxidative stress are involved in the pathogenesis of any renal diseases. Angiotensin-converting enzyme inhibitors have multi-directional renoprotective effects. In this study, we aimed to investigate whether lisinopril treatment has any biochemical alterations on renal tissue in L-NAME (Nε-nitro-L-arginine methyl ester) induced hypertension model. Twenty-eight Sprague-Dawley rats were included in this study and divided into four equal groups (n = 7): control group, L-NAME treated group (75 mg/kg/day), L-NAME plus lisinopril treated group and only lisinopril treated group (10 mg/kg/day). L-NAME and lisinopril were continued for 6 weeks. Systolic blood pressures were measured by using tail cuff method. In biochemical analysis, malondialdehyde (MDA, an index of lipid peroxidation) levels, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in renal tissues were used as markers of oxidative stress-induced renal impairment. Microalbumin and N-acetyl-β-D-glucosaminidase (NAG) in urine were determined as markers of renal tubular damage related to hypertension. Chronic L-NAME administration resulted in a significant depletion of serum nitric oxide (NO). When compared with control group, serum creatinine, microalbumin, urine NAG, renal tissue MDA level, and CAT activities were significantly high, while renal tissue SOD and GSH-Px activities low in L-NAME group. In the L-NAME plus lisinopril treated group, serum creatinine, microalbumin and urine NAG, renal MDA level and CAT activity decreased, whereas SOD, GSH-Px activities in renal tissue and serum NO levels were increased. Thus, lisinopril treatment reversed these effects. There were not any significant difference between L-NAME plus lisinopril treated group and control group concerning serum creatinine, renal tissue MDA level and SOD, GSH-Px, CAT activities. These results suggest that lisinopril could diminish biochemical alterations in L: -NAME induced hypertensive renal damage that occurs by oxidative stress.

Could nephrotoxicity due to colistin be ameliorated with the use of N-acetylcysteine?

The protective effect of N-acetylcysteine (NAC) on nephrotoxicity due to contrast nephropathy and reperfusion-induced ischemia has been reported in experimental models. However, its efficacy on colistin-induced nephrotoxicity has not been elucidated yet. The primary aim of this study was to evaluate the nephrotoxic effect of colistin and to investigate the possible protective effect of NAC on colistin-induced nephrotoxicity. The secondary aim was to research the systemic effects of nephrotoxicity-induced oxidative stress on the lung. Eighteen female Sprague-Dawley rats were randomly assigned and were given (a) 1 ml/kg sterile saline, (b) 300,000 IU/kg/day colistin, and (c) 300,000 IU/kg/day colistin and 150 mg/kg NAC for six consecutive days. Plasma blood urea nitrogen (BUN), creatinine, urinary creatinine, urinary protein, plasma TNF-alpha levels, renal tissue superoxide dismutase (SOD) and malondialdehyde (MDA) activity and immunocytochemical findings were evaluated. Colistin exerted nephrotoxicity and achieved a significant increase in plasma BUN and creatinine levels and renal tissue SOD levels. NAC exhibited no significant effect on biochemical parameters but reduced renal tissue SOD level and reversed immunocytochemical staining of inducible nitric oxide synthase (i-NOS) and neurotrophin-3. Increased oxidative stress in the lung tissue of the rats treated with colistin has also been documented. Additionally, NAC significantly reduced the immunostaining of endothelial NOS (e-NOS) and i-NOS in the lung tissue. Colistin-induced renal toxicity may be attributable to oxidative damage. The combined treatment of colistin plus NAC seems to have a beneficial role in restoration of the oxidant injury which may be related to its antioxidant effect.

Orthosiphon grandiflorum has a protective effect in a calcium oxalate stone forming rat model

This study amied to investigate the effects of Orthosiphon grandiflorum on the renal tubular cell injury induced by oxalate and the inhibitory effects of O. grandiflorum on urinary deposit formation in an animal model and compared the results with those from a potassium citrate treatment. Rats were divided into three groups: an untreated stone-forming group, an O. grandiflorum-treated stone-forming group and a potassium citrate-treated stone forming group. Ethylene glycol (0.5%) was administered to the rats during the last week, and vitamin D3 (0.5 mum) was force fed to induce hyperoxaluria and kidney calcium oxalate crystal deposition. Twenty-four hour urine samples were collected before and after inducing crystal deposits. Rats were killed and both kidneys were harvested after 3 weeks. Bisected kidneys were examined under a polarized light microscope to determine the number of crystals. The renal tissue superoxide dismutase and catalase levels were measured by Western blot. Oxidative stress was examined by 8-OHdG immunohistofluorescence. O. grandiflorum and potassium citrate have the ability to alkalinize urine. Among all groups, the number of crystal deposits and the level of 8-OHdG staining decreased significantly in the O. grandiflorum-treated stone forming group, as compared to the other groups. Superoxide dismutase and catalase levels also increased significantly in the O. grandiflorum-treated stone-forming group, as compared with the untreated stone-forming group. The results indicate that O. grandiflorum has a significant inhibitory effect on crystal deposition in the calcium oxalate-stone-forming rat model.

Effects of Gum Arabic in rats with adenine-induced chronic renal failure

Gum Arabic (GA [Acacia senegal]) is reputed, in Arabian medicinal practices, to be useful in treating patients with chronic renal failure (CRF), albeit without strong scientific evidence. We have previously shown that GA had no significant effect in rats with CRF induced by surgical nephrectomy. Here, we used another animal model of human CRF (feeding adenine at a concentration of 0.75%(w/w) for four weeks) to test the effect of GA on CRF. Renal morphology and measurements of plasma concentrations of urea and creatinine (Cr), and Cr clearance, in addition to urinary volume, osmolarity and protein concentrations, and N-acetylglucosamine and lactate dehydrogenase activities were performed. Interleukin-6 and the total antioxidant levels in urine, as well as the activity of superoxide dismutase in renal tissues, were estimated. Adenine feeding resulted in marked renal damage. GA (6%(w/v) and 12%(w/v) in drinking water for four consecutive weeks) significantly ameliorated the adverse biochemical alterations indicative of renal failure, abated the decrease in body weight and reduced the glomerular, tubular and interstitial lesions induced by adenine. Our study provides evidence that GA attenuated renal dysfunction in this model of CRF, suggesting a promising potential for it in protecting against renal failure progression. The mechanism(s) of this nephroprotection is uncertain but may involve anti-oxidant and/or anti-inflammatory actions.