Renal Malondialdehyde Concentration Research Articles

Quinacrine Ameliorates Cisplatin-Induced Renal Toxicity via Modulation of Sirtuin-1 Pathway.

Renal toxicity is a serious side effect that hinders the use of cisplatin, a commonly used and effective chemotherapeutic agent. Meanwhile, quinacrine is an FDA approved drug that has been stated for its anti-inflammatory effect. Thus, we investigated the ameliorative effect of quinacrine against cisplatin-induced renal toxicity. Single intraperitoneal (i.p.) 10 mg/kg cisplatin administration induced renal injury in rats. Our results showed that 10 mg/kg/day quinacrine decreased the mortality rate of rats from 46.15% (cisplatin group) to 12.5%, and significantly decreased renal tissue fibrosis, relative kidney to body weight ratio, serum creatinine and urea levels compared with the cisplatin group. Indeed, quinacrine significantly decreased renal malondialdehyde concentration and increased renal total antioxidant capacity, compared with the cisplatin group. Furthermore, quinacrine caused significant upregulation of renal sirtuin-1 (SIRT-1) with significant downregulation of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α). Moreover, quinacrine significantly blocked cisplatin-induced apoptosis, which was made evident by downregulating renal apoptotic proteins (BAX and p53) and upregulating the renal anti-apoptotic protein BCL2, compared with the cisplatin group. In conclusion, this study demonstrates, for the first time, that quinacrine alleviates cisplatin-induced renal toxicity via upregulating SIRT-1, downregulating inflammatory markers (ICAM-1 and TNF-α), reducing oxidative stress, and inhibiting apoptosis.

Quinacrine ameliorated Cisplatin‐induced renal toxicity via modulation of Sirtuin‐1 and its downstream inflammatory and apoptosis pathways

Cisplatin is an effective and widely used chemotherapeutic agent, while underlying renal toxicity is a major limitation for its use. Quinacrine, is an FDA approved antimalarial agent that is known for its anti-inflammatory effect. It has been shown that quinacrine is therapeutically beneficial in cancer, lupus erythematosus and cutaneous sarcoidosis, however, its use to protect against cisplatin toxicity has not been investigated. In this study, we investigated the ameliorative effect of quinacrine against cisplatin induced renal toxicity in rats and the potential molecular mechanism of quinacrine action. Cisplatin toxicity was induced by a single intraperitoneal injection of 10 mg/kg at day 5. Reno protective effect of quinacrine was assessed by intraperitoneal injection of 10 mg/kg/day for the whole-time course of the experiment (10 days). Quinacrine increased rats’ survival rate from 50% (cisplatin group) to 87.5%, with significant decrease in relative kidney weight to body weight, serum creatinine and urea levels in addition to significant reduction in renal tissue fibrosis compared with cisplatin group. Moreover, quinacrine attenuated cisplatin-induced oxidative stress upregulation as indicated by significant decrease in renal malondialdehyde concentration and significant increase in renal total antioxidant capacity compared with cisplatin group. Mechanistically, quinacrine significantly upregulated renal tissue concentration of sirtuin-1 (Sirt-1) which significantly downregulated the inflammatory markers: Intercellular Adhesion Molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α). In addition, quinacrine significantly prevented cisplatin-induced apoptosis as evident by decreased renal tissue expression of caspases (1, 3, 8 and 9), decreased the apoptotic proteins BAX and P53 and increased the anti-apoptotic protein BCL2 compared with cisplatin group. Altogether, this study proposes, for the first time, that quinacrine ameliorated cisplatin-induced renal toxicity via upregulation of Sirt-1, downregulation of inflammatory markers (ICAM-1 and TNF-α), restoring oxidative balance and suppressing apoptosis.

Modulation of the Lipid Profile, Hepatic and Renal Antioxidant Activities, and Markers of Hepatic and Renal Dysfunctions in Alloxan-Induced Diabetic Rats by Virgin Coconut Oil.

Research studies that holistically investigated the effect of administration of Virgin Coconut Oil (VCO) on diabetic humans or animals are limited in literature. To investigate the effect of administration of VCO on lipid profile, markers of hepatic and renal dysfunction, and hepatic and renal antioxidant activities of alloxan induced diabetic rats. Twenty-four male albino rats were used, and they were divided into four groups of six rats each. Group 1 (Normal Control, NC) received distilled water (1 mL/kg); Group 2 (VCO Control) received VCO (5 mL/kg); Group 3 (Diabetic Control, DC) received distilled water (1 mL/kg); Group 4 (Test Group, TG) received 5 ml/kg of VCO. There were no significant differences in blood glucose, body weights, relative liver weights, relative kidney weights, hepatic and renal Superoxide Dismutase (SOD) activities, Malondialdehyde (MDA), albumin, aspartate Amino Transaminase (AST), alanine Amino Transaminase (ALT), Alkaline Phosphatase (ALP), urea, creatinine, uric acid, total cholesterol, triacylglycerol, Very Low Density Lipoprotein cholesterol (VLDL) and Low Density Lipoprotein cholesterol (LDL) concentrations; significant increases in renal Glutathione (GSH), hepatic catalase, Glutathione Peroxidase (GPx) and GSH but significant reduction in renal GPx and catalase activities of VCO control group compared with NC group. There were significant increases in blood glucose, relative liver and kidney weights, hepatic GPx, hepatic and renal MDA concentration, ALP, AST, ALT, urea, creatinine, uric acid, triacylglycerol, total cholesterol, LDL and VLDL concentrations; and significant decreases in body weight, hepatic SOD and GSH activities and albumin concentration but no significant difference in hepatic catalase activity of DC group compared with NC group. Administration of VCO to diabetic rats positively modulated these parameters compared with the diabetic control. The study showed the potentials of VCO in the management of hyperlipidemia, renal and hepatic dysfunctions imposed by hyperglycemia and by oxidative stress in diabetic rats.

Coenzyme Q10 Attenuates Cisplatin-induced Nephrotoxicity Through Counteracting Oxidative Stress and Inflammation

Background: Cisplatin is an anticancer drug used in the management of solid tumors, however, dose-related nephrotoxicity is one of its major problems. Agents having antioxidants, antiinflammatory and/or antiapoptotic activities may thus represent potential therapeutic options to avoid cisplatin-induced nephrotoxicity. Among these agents, coenzyme Q10 has several pharmacological properties including antioxidant, anti-inflammatory and/or anti-apoptotic effects. Objective: The current study aimed to examine whether coenzyme Q10 could attenuate cisplatininduced nephrotoxicity or not. Methods: 24 adult rats were randomly separated into three groups (8 rats per group). The first one was the control group, rats receiving vehicle (olive oil) intraperitoneally. The second group was Cisplatin treated group, rats were receiving 13 mg/kg of Cisplatin intraperitoneally as a single dose. The third group (Cisplatin + Coenzyme Q10), rats were receiving 13 mg/kg as a single intraperitoneal dose of Cisplatin and coenzyme Q10 daily for six consecutive days (10 mg/kg intraperitoneally). Results: Cisplatin caused significant increases in serum creatinine and severe histological lesions. Cisplatin treated group also showed a significant elevation in renal malondialdehyde concentration as a marker of oxidative stress; renal tumor necrosis factor-alpha concentration as a marker of inflammation; and Kidney injury molecule -1 concentration. Coenzyme Q10 significantly attenuated cisplatininduced nephrotoxicity through lowering serum creatinine and improving nephrotoxicity histological scores. Coenzyme Q10 also significantly reduced the renal concentration of MDA, TNF-α and KIM-1 relative to cisplatin treated group. Conclusions: Coenzyme Q10 has a potential nephroprotective effect against cisplatin-induced nephrotoxicity that was demonstrated by biochemical and histopathological analysis.

Protective Effect of Angelica sinensis Extract and Origanum majorana Oil on Hepatic and Renal Toxicities Induced by Nickel Chloride in Male Albino Rats

The present study was accomplished to evaluate the efficacy of Angelica sinensis root extract and Origanum majorana oil on subchronic toxicity of nickel chloride (NiCl2) in albino rats by studying the changes in the biochemical parameters, lipid peroxidation and antioxidant status related to the liver and kidneys. This study was carried out on sixty male albino rats with average body weight (120 ± 10 g), which were divided into 6 equal groups. Gp.(1): were kept as control on distilled water, rats in Gp. (2) received NiCl2 (0.75 mg/kg BW), Gp. (3) received A. sinensis root extract (300 mg/kg BW) and Gp. (4) received O. majorana oil (0.5 ml/kg BW). NiCl2 intoxicated rats in Gp. (5) and Gp. (6) were administered A. sinensis root extract and O. majorana oil at the same former doses, respectively. The treatments were daily and orally for 4 weeks. Blood and tissue samples were collected for performing the different experimental analysis after 4 weeks from starting the treatments. Comparing with the control group, results showed that NiCl2 significantly increased serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities and serum bilirubin, triglycerides, total cholesterol, urea and creatinine concentrations, besides hepatic and renal malondialdehyde concentration, while serum total proteins, albumin and hepatic and renal glutathione, glutathione peroxidase, superoxide dismutase and catalase levels were significantly decreased. A. sinensis root extract and O. majorana oil has no adverse effects and worked on amelioration the various alterations in estimated analytes in combined treated groups. In conclusion, NiCl2 caused hepatic and renal injuries besides the induction of lipid peroxidation and reducing the antioxidant enzymes activities in these organs. Moreover, both of A. sinensis root extract and O. majorana oil provided significant protection against harmful effects of NiCl2 with superiorty of A. sinensis root extract

Administration of hydrogen sulfide protects ischemia reperfusion-induced acute kidney injury by reducing the oxidative stress.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury. Hydrogen sulfide (H2S) has been known as a novel gaseous signaling molecule. The aim of this study was to investigate whether the efficacy of H2S in protecting against renal IRI is through its antioxidative effect. In this study, rats were randomized into Sham, IR, or sodium hydrosulfide (NaHS, an H2S donor) groups. To establish a model of renal IRI, both renal arteries were occluded for 55min and then declamped to allow reperfusion for 24h. Rats in the NaHS group received intraperitoneal injections of 75μmol/kg NaHS 10min before the onset of ischemia and immediately after the onset of reperfusion. Sham group underwent laparotomy without cross-clamping of renal pedicles. After reperfusion, plasma and renal tissue samples were collected for functional, histological, and oxidative stress evaluation. The IR group exhibited significant rise in plasma creatinine, blood urea nitrogen (BUN), renal malondialdehyde (MDA) concentration, and significant reduction of renal superoxide dismutase (SOD) activity. Treatment with NaHS reduced the levels of plasma creatinine, BUN, renal MDA concentration, and increased SOD activity in the kidneys. NaHS improved renal histological changes in comparison to IR group. Our data demonstrated that H2S can protect against renal IRI and that its therapeutic effects may be mediated by reducing oxidative stress.

Effect of paricalcitol and enalapril on renal inflammation/oxidative stress in atherosclerosis.

To investigate the protective effect of paricalcitol and enalapril on renal inflammation and oxidative stress in ApoE-knock out mice. Animals treated for 4 mo as group (1) ApoE-knock out plus vehicle, group (2) ApoE-knock out plus paricalcitol (200 ng thrice a week), (3) ApoE-knock out plus enalapril (30 mg/L), (4) ApoE-knock out plus paricalcitol plus enalapril and (5) normal. Blood pressure (BP) was recorded using tail cuff method. The kidneys were isolated for biochemical assays using spectrophotometer and Western blot analyses. ApoE-deficient mice developed high BP (127 ± 3 mmHg) and it was ameliorated by enalapril and enalapril plus paricalcitol treatments but not with paricalcitol alone. Renal malondialdehyde concentrations, p22(phox), manganese-superoxide dismutase, inducible nitric oxide synthase (NOS), monocyte chemoattractant protein-1, tumor necrosis factor-alpha and transforming growth factor-β1 levels significantly elevated but reduced glutathione, CuZn-SOD and eNOS levels significantly depleted in ApoE-knock out animals compared to normal. Administration of paricalcitol, enalapril and combined together ameliorated the renal inflammation and oxidative stress in ApoE-knock out animals. Paricalcitol and enalapril combo treatment ameliorates renal inflammation as well as oxidative stress in atherosclerotic animals.

English

The aim of the study was to investigate the effects of taurine on biochemical parameters in male Wistar rats co-exposed to chlorpyrifos and lead. Fifty rats were divided into five groups of ten rats each. The distilled water (DW) group received distilled water and the soya oil (SO) group received soya oil (1 ml/kg). Other groups were treated sequentially with taurine (50 mg/kg), chlorpyrifos (4.25 mg/kg, 1/20th LD50) and lead (233.25 mg/kg, 1/20th LD50), and the last group received taurine (50 mg/kg), chlorpyrifos (4.25 mg/kg) and lead (233.25 mg/kg). The treatments were administered once daily by oral gavage. The rats were sacrificed and blood samples were collected after 16 weeks. The serum samples were analyzed for proteins, enzymes, urea and creatinine concentration. The hepatic and renal malondialdehyde concentration and activities of hepatic and renal antioxidant enzymes were evaluated. The results indicated that chronic co-administration of chlorpyrifos (CPF) and lead acetate (LA) induced biochemical alterations in the rats. It is proposed that taurine antioxidant (TA) decreased the alterations in the biochemical parameters partly through its antioxidant, hepatoprotective and nephroprotective properties. It is concluded that taurine is a useful prophylactic agent against biochemical toxicity in individuals that are constantly co-exposed to chlorpyrifos and lead in the environment.   Key words: Taurine, chlorpyrifos, lead, oxidative stress, biochemical effects.

Cysteinyl leukotriene receptor antagonism alleviates renal injury induced by ischemia-reperfusion in rats

BackgroundRenal inflammation has an important role in the development of ischemia-reperfusion injury of the kidney. Cysteinyl leukotrienes have been implicated in many inflammatory conditions. The aim of this study was to investigate the ability of the cysteinyl leukotriene receptor blocker, zafirlukast, to alleviate renal dysfunction and injury in a rat model of renal ischemia-reperfusion injury. MethodsWe induced renal ischemia for 45 min, followed by 24 h reperfusion. We gave zafirlukast at a dose of 20 mg/kg/d for 3 d before ischemia-reperfusion. At the end of the reperfusion (24 h), we collected blood samples to measure blood urea nitrogen, creatinine, tumor necrosis factor-α, intercellular adhesion molecule-1, and nitrite/nitrate. We took kidney samples for histological and immunohistochemical assessment, and to measure malondialdehyde, glutathione content, and myeloperoxidase activity. ResultsInduction of renal ischemia-reperfusion resulted into renal dysfunction, as indicated by elevated levels of blood urea nitrogen and serum creatinine, serum nitrite and nitrate, serum tumor necrosis factor-α, and intercellular adhesion molecule-1. An oxidative stress marker, renal malondialdehyde concentration, was increased, whereas renal reduced glutathione content was decreased. Myeloperoxidase activity, suggestive of neutrophil infiltration, was elevated in renal tissues. Histological changes confirmed these biochemical changes, as did P-selectin overexpression in renal tissues subjected to ischemia-reperfusion. Administration of zafirlukast before ischemia-reperfusion improved renal functions and reduced serum levels of nitrite and nitrate, tumor necrosis factor-α, and intercellular adhesion molecule-1, renal concentration of myeloperoxidase activity, and malondialdehyde concentration, whereas increased renal reduced glutathione concentration. Moreover, zafirlukast reduced histopathological features of tubular injury and P-selectin overexpression in both cortex and medulla. ConclusionsThese results demonstrate that zafirlukast significantly reduces the severity of ischemic acute renal failure, probably via anti-inflammatory action, reduction of neutrophil infiltration into renal tissues, and oxidative stress subsequent to an attenuation of P-selectin expression.

Changes in Serum and Renal Vitamin E Levels in Deoxycorticosterone Acetate–Salt Hypertensive Rats

Hypertension is an important risk factor for the progression of chronic renal disease, which may result in the development of end-stage renal disease. Since reactive oxygen species are implicated in the induction of hypertension, antioxidants have been used to reduce blood pressure and renal impairment in animal models and in human hypertension. However, the available data are not conclusive. To investigate oxidative stress in hypertension, we evaluated renal and serum vitamin E levels as the most effective antioxidant to reduce lipid peroxidation by high-performance liquid chromatography among rats subjected to deoxycorticosterone acetate (DOCA)-salt treatment for 4 weeks. Renal levels of malondialdehyde (MDA) as a marker of cell lipid peroxidation were also assayed in treated rats. Systolic blood pressure (SBP) was measured in conscious rats by the tail-cuff method using a PowerLab/4sp data acquisition system. SBP increased significantly in DOCA-salt-treated rats compared to the sham group after 4 weeks of treatment. Serum vitamin E levels were significantly lower and renal MDA concentrations significantly higher in treated compared to sham rats. However, renal vitamin E levels were also significantly higher among treated compared to sham rats. Decreased plasma vitamin E levels and increased renal MDA levels show systemic and local oxidative stress in DOCA-salt-treated rats. However, the higher renal vitamin E level suggested a local compensatory mechanism. Vitamin E administration might be appropriate, as significant decreases in vitamin E levels were observed in the serum of DOCA-salt-treated rats.

Hypoperfusion-induced acute renal failure in the rat: an evaluation of oxidant tissue injury.

Reactive oxygen species (ROS) have been reported to be critical cellular mediators of experimental ischemic acute renal failure (ARF). This conclusion is based on observations that in the renal artery occlusion (RAO) model of ARF, antioxidant drugs confer protection and that renal malondialdehyde (MDA) concentrations, an index of lipid peroxidation, rise in the postischemic period. Human ischemic ARF is most often due to hypoperfusion, not to total blood flow interruption. Therefore, the goal of this study was to determine whether ROS also mediate hypoperfusion-induced renal injury. Renal hypoperfusion was induced in rats by suprarenal partial aortic ligation, lowering renal perfusion pressure to 20-25 mm Hg for 45 minutes. Renal MDA concentrations were measured 15 minutes after ligation release. Renal function and morphology were assessed 24 hours after hypoperfusion in control rats and in rats pretreated with antioxidant agents (allopurinol, superoxide dismutase, dimethyl-thiourea, glutathione, and catalase), a majority of which have been shown to lessen RAO-induced ARF. Hypoperfusion caused no rise in renal MDA concentrations (p = 0.54). Control ARF rats developed significant azotemia (blood urea nitrogen 119 +/- 6 mg/dl; creatinine 3.3 +/- 0.37 mg/dl) and widespread tubular necrosis by 24 hours after surgery. None of the antioxidants, administered singly or in combination, lessened the ischemic damage. Therefore, renal MDA concentrations do not rise in hypoperfusion ARF, and antioxidants do not confer protection. This indicates that previous evidence for ROS as mediators of ischemic renal injury is restricted to the RAO model of ARF, which does not closely simulate most human ischemic renal injury.

Effect of superoxide dismutase on glomerular nephritis

The antiinflammatory effect of superoxide dismutase was studied in rats with kidney intoxication induced by the injection of nephrotoxic serum. The urinary excretion of protein was increased significantly by the administration of an intravenous injection of nephrotoxic serum. The daily injection of superoxide dismutase significantly suppressed the increase in urinary excretion of protein. The injection of nephrotoxic serum increased the renal malondialdehyde level by 3-fold compared to the level in the control rats. The daily injection of superoxide dismutase also significantly suppressed the renal malondialdehyde concentration. The change of serum Cu,Zn-superoxide dismutase level and tissue distribution after the intramuscular injection of this enzyme was investigated by immunoassay. Human Cu,Zn-superoxide dismutase localized in kidney exclusively and reached maximum concentration at about 3 hr after the injection. From these results, we propose that superoxide dismutase, which is a scavenger of superoxide anion radicals, inhibits lipid hydroperoxidation in the kidney induced by activated oxygen, and thus protects the renal cells from the damage induced by the injection of nephrotoxic serum.