Oxidative Stress In Rat Kidney Research Articles

A study on bisphenol induce renal damage and role of vitamin c as an antioxidant on bisphenol induced renal damage in wistar rats. A case control study.

Bisphenol A (BPA) is considered one of the most common industrial manufactured chemicals and a pollutant. oxidative stress has been induced by bisphenol by dysregulate the cytokines. Oxidative stress induced by BPA is known to affect the brain, liver, and kidneys. Vitamin C is an important dietary antioxidant which is known decreases the oxidative stress induced by reactive oxygen species. Hence the current study was focused to evaluate the damaging effect of BPA on kidney and the role of ascorbic acid on BPA induced kidney toxicity. There were four groups of rats(6 rats in each); Group 1: Control Group (Olive oil treated) Group 2:(Vitamin C treated), Group 3: (Bispenol treated), Group 4: (Vitamin C + Bispenol treated). One kidney homogenized to measure Melonaldihyde level and glutathione and other kidney was used to study the histopathlogical parmeters. Biochemical estimation of serum electrolyte was done by commercially available kits using spectrophotometer. Animals exposed to Bisphenol showed fall in the level of GSH and increase in MDA level as well as fall in serum sodium and potassium level. Biochemical results were supported by histo-pathalogical changes. Pre-treatment with Vitamin C showed an rise in the level of GSH, sodium and potassium level and fall in MDA. Vitamin C pre-treatment also showed some beneficial changes in histology of kidney also. Our result demonstrated that exposure to Bisphenol induced oxidative stress in rat kidney and vitamin C could act as an antioxidant protecting against BPA induced oxidative stress.

Antioxidant and Anti-inflammatory Effects of α-Lipoic Acid on Lipopolysaccharide-induced Oxidative Stress in Rat Kidney

α-Lipoic acid (α-LA) is a naturally occurring organosulfur component. Oxidative stress plays an essential role in the pathogenesis of various diseases, such as kidney and cardiovascular diseases, diabetes, neurodegenerative disorders, cancer and aging. Kidneys are especially vulnerable to oxidative stress and damage. The aim of the study was to evaluate the effect of α-LA on lipopolysaccharide (LPS)-induced oxidative stress parameters in rat kidneys. The experimental rats were divided into four groups: I—control (0.9% NaCl i.v.); II—α-LA (60 mg/kg b.w. i.v.); III—LPS (30 mg/kg b.w. i.v.); and IV—LPS + LA (30 mg/kg b.w. i.v. and 60 mg/kg b.w. i.v., respectively). In kidney homogenates the concentration of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), sulfhydryl groups (−SH), total protein, superoxide dismutase (SOD), total glutathione (tGSH), reduced glutathione (GSH), glutathione disulphide (GSSG) and the GSH/GSSG ratio were determined. In addition, the levels of tumour necrosis factor (TNF)-α, and interleukin (IL)-6 were measured to assess inflammation and was estimated kidney oedema. Studies have shown that α-LA administered after LPS administration attenuated kidney oedema and significantly decreased TBARS, H2O2, TNF-α, and IL-6 levels in rat kidneys. α-LA also resulted in increase −SH group, total protein, and SOD levels and ameliorated the GSH redox status when compared to the LPS group. The results suggest that α-LA plays an important role against LPS-induced oxidative stress in kidney tissue as well as downregulating the expression of pro-inflammatory cytokines.Graphical

Impacts of High Fructose Diet and Chronic Exercise on Nitric Oxide Synthase and Oxidative Stress in Rat Kidney.

Chronic exercise (Ex) exerts antihypertensive and renoprotective effects in rats fed a high fructose diet (HFr). To elucidate the mechanisms, the impacts of an HFr and Ex on the nitric oxide (NO) system and oxidative stress in the kidney were examined. Rats were fed a control diet or an HFr, and a part of the HFr-fed rats underwent treadmill running for 12 weeks. The HFr did not affect nitrate/nitrite (NOx) levels in plasma and urine, and Ex increased the NOx levels. The HFr increased thiobarbituric acid reactive substance (TBARS) levels in plasma and urine, and Ex decreased the HFr-increased TBARS levels in plasma. The HFr increased the neuronal and endothelial NO synthase (nNOS and eNOS) expressions, and Ex enhanced the HFr-increased eNOS expression. The HFr inhibited the eNOS phosphorylation at serine 1177, and Ex restored the HFr-inhibited eNOS phosphorylation. The HFr increased xanthine oxidase and NADPH oxidase activities, and Ex restored the HFr-increased xanthine oxidase activity but enhanced the HFr-increased NADPH oxidase activity. The HFr increased the nitrotyrosine levels, and Ex attenuated the HFr-increased levels. These results indicate that although Ex enhances the HFr-increased eNOS expression and NADPH oxidase activity, an HFr inhibits renal eNOS phosphorylation and NO bioavailability, whereas Ex ameliorates them.

Direct Pharmacological Correction of Oxidative Stress in Rat Kidneys Does Not Facilitate Diabetic Nephropathy

The aim of this study was to evaluate the effect of alpha-tocopherol acetate (ATA) on the activity of free-radical oxidation (FRO) in renal tissue and renal function in rats with experimental streptozotocin (STZ)-induced diabetes mellitus (DM). Methods and Results: Experiments were conducted on 22 male Wistar rats aged 60-100 days and weighing 250-300g. The animals were divided into two groups (Group 1 (control) and Group 2 (experimental. To induce DM, the animals were injected intraperitoneally 1ml of STZ solution in the citrate buffer at a dose of 65mg/kg. For more selective modeling of type 2 DM, the rats were previously injected with an intraperitoneal solution of cytoflavin based on a nicotinamide dose of 115mg/kg In Croup 2, ATA was administered in the period from the fifth to eighth weeks, inclusive, intragastrically through a tube at a daily dose of 300mg/kg. Experiments showed that after a 4-week course of ATA, the concentration of thiobarbiturate-reactive products in the kidney tissues of the rats in Group 2 was 5.3 times lower than in Group 1. The activity of all antioxidant enzymes did not differ between the two groups. In both groups, during all 8 weeks of the experiment, the levels of renal excretion of glucose, protein, and creatinine significantly exceeded the initial level, while the level of diuresis remained stable. Conclusion: The long-term administration of ATA in experimental streptozotocin (STZ)-induced DM is accompanied by a significant suppression of the activity of the FRO processes in the kidneys, but does not lead to an improvement in the course of DN.

Evaluation of polyherbal formulation against isoniazid and rifampicin induced oxidative stress in rat kidney

The present study deals with oxidative stress in rat kidneys upon administration of Isoniazid (INH) and Rifampicin (RIF), and the attenuative effect of polyherbal formulation Heptoplus. Heptoplus is a polyherbal drug that contains phyllanthin as the active ingredient. Rats were intoxicated with INH and RIF and Heptoplus was orally fed to rats along with INH and RIF. Body weight, serum biochemical, antioxidant status, mitochondrial enzyme activity, lysosomal enzyme leakage and the histopathological impact were studied in the rat kidneys. Body and kidney weight of untreated rats showed deviation, but on treatment, they maintained their normal weight. Untreated rats showed altered serum urea and creatinine levels with deviated antioxidant status and enzymes leakages from lysosomes and decreased mitochondrial enzyme activity in kindey. But Heptoplus treatment allowed the rats to maintain their biochemical indices in blood and kidney at near normal level. Histopathological reports revealed INH- and RIF -induced oxidative stress was not in sufficient amount to incur any significant damage at the tissue level. Hence, both treated and untreated rat kidneys exhibits normal architecture. In conclusion, Heptoplus treatment protects the kidney of rats from the INH- and RIF- induced oxidative stress.

Targeting ROS/NF-\u03baB signaling pathway by the seedless black Vitis vinifera polyphenols in CCl4-intoxicated kidney, lung, brain, and spleen in rats

Carbon tetrachloride (CCl4) is an abundant environmental pollutant that can generate free radicals and induce oxidative stress in different human and animal organs like the kidney, lung, brain, and spleen, causing toxicity. The present study evaluated the alleviative mechanism of the isolated polyphenolic fraction from seedless (pulp and skin) black Vitis vinifera (VVPF) on systemic oxidative and necroinflammatory stress in CCl4-intoxicated rats. Here, we found that the administration of VVPF to CCl4-intoxicated rats for ten days was obviously ameliorated the CCl4-induced systemic elevation in ROS, NO and TBARS levels, as well as MPO activity. Also, it upregulated the cellular activities of the enzymatic (SOD, and GPx) and non-enzymatic (TAC and GSH) antioxidants. Furthermore, the gene expression of the ROS-related necroinflammatory mediators (NF-κB, iNOS, COX-2, and TNF-α) in the kidney, brain, and spleen, as well as IL-1β, and IL-8 in the lung were greatly restored. The histopathological studies confirmed these biochemical results and showed a noticeable enhancing effect in the architecture of the studied organs after VVPF intake. Thus, this study indicated that VVPF had an alleviative effect on CCl4-induced necroinflammation and oxidative stress in rat kidney, lung, brain, and spleen via controlling the ROS/NF-κB pathway.

Betaine attenuates sodium arsenite-induced renal dysfunction in rats

Exposure to higher levels of arsenic is a serious threat affecting human health worldwide. We investigated the protective role of betaine (N,N,N-trimethylglycine) against sodium arsenite-induced renal dysfunction in rats. Sodium arsenite (5 mg/kg, oral) was given to rats for 4 weeks to induce nephrotoxicity. Betaine (125 and 250 mg/kg, oral) was administered in rats for 4 weeks along with sodium-arsenite feeding. Arsenic-induced renal dysfunction was demonstrated by measuring serum creatinine, creatinine clearance, urea, uric acid, potassium, fractional excretion of sodium, and microproteinuria. Oxidative stress in rat kidneys was determined by assaying thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels. Furthermore, hydroxyproline assay was done to assess renal fibrosis in arsenic intoxicated rats. Hematoxylin-eosin and picrosirius red staining revealed pathological alterations in rat kidneys. Renal endothelial nitric oxide synthase (eNOS) expression was determined by immuno-histochemistry. Concurrent administration of betaine abrogated arsenic-induced renal biochemical and histological changes in rats. Betaine treatment significantly attenuated arsenic-induced decrease in renal eNOS expression. In conclusion, betaine is protective against sodium arsenite-induced renal dysfunction, which may be attributed to its anti-oxidant activity and modulation of renal eNOS expression in rat kidneys.

PO-1913 Effects of Nigella sativa oil and thymoquinone on radiation-induced oxidative stress in rat kidney

PO-1913 Effects of Nigella sativa oil and thymoquinone on radiation-induced oxidative stress in rat kidney

Time Course Effects of Dietary Vitamin D on Diethylnitrosamine-Induced Oxidative Stress in Rat Kidney

Time Course Effects of Dietary Vitamin D on Diethylnitrosamine-Induced Oxidative Stress in Rat Kidney

Ameliorative role of inducible nitric oxide synthase inhibitors against sodium arsenite-induced renal and hepatic dysfunction in rats

Arsenic exposure causes immense health distress by increasing risk of cardiovascular abnormalities, diabetes mellitus, neurotoxicity, and nephrotoxicity. The present study explored the role of inducible nitric oxide synthase (iNOS) inhibitors against sodium arsenite-induced renal and hepatic dysfunction in rats. Female Sprague Dawley rats were subjected to arsenic toxicity by administering sodium arsenite (5 mg/kg/day, oral) for 4 weeks. The iNOS inhibitors, S-methylisothiourea (10 mg/kg, i.p.) and aminoguanidine (100 mg/kg, i.p.) were given one hour before sodium arsenite administration in rats for 4 weeks. Sodium arsenite led rise in serum creatinine, urea, uric acid, electrolytes (potassium, fractional excretion of sodium), microproteinuria, and decreased creatinine clearance (p < 0.001) indicated renal dysfunction in rats. Arsenic-intoxication resulted in significant oxidative stress in rat kidneys, which was measured in terms of increase in lipid peroxides, superoxide anion generation and decrease in reduced glutathione (p < 0.001) levels. A threefold increase in renal hydroxyproline level in arsenic intoxicated rats indicated fibrosis. Hematoxylin–eosin staining indicated tubular damage, whereas picrosirius red staining highlighted collagen deposition in rat kidneys. S-methylisothiourea and aminoguanidine improved renal function and attenuated arsenic led renal oxidative stress, fibrosis, and decreased the kidney injury score. Additionally, arsenite-intoxication resulted in significant rise in hepatic parameters (serum aspartate aminotransferase, alanine transferase, alkaline phosphatase, and bilirubin (p < 0.001) along with multi-fold increase in oxidative stress, fibrosis and liver injury score in rats, which was significantly (p < 0.001) attenuated by concurrent administration of iNOS inhibitors). Hence, it is concluded that iNOS inhibitors attenuate sodium arsenite-induced renal and hepatic dysfunction in rats.

Fenofibrate attenuates ischemia reperfusion-induced acute kidney injury and associated liver dysfunction in rats.

Ischemia/reperfusion (I/R) is one of the common reasons for acute kidney injury (AKI) and we need to develop effective therapies for treating AKI. We investigated the role of fenofibrate against I/R-induced AKI and associated hepatic dysfunction in rats. In male wistar albino rats, renal pedicle occlusion for 40 min and 24 h reperfusion resulted in AKI. I/R-induced AKI was demonstrated by measuring serum creatinine, creatinine clearance, urea, uric acid, potassium, fractional excretion of sodium and urinary microproteins. Oxidative stress in rat kidneys was quantified by assaying superoxide anion generation, thiobarbituric acid reactive substances, and reduced glutathione levels. AKI-induced hepatic damage was quantified by assaying serum aminotransferases, alkaline phosphatase and bilirubin levels. Moreover, serum cholesterol, high density lipoprotein and triglycerides were quantified. Hematoxylin-eosin staining of renal and hepatic tissues was done and the kidney and liver injury scores were determined. Immunohistology of endothelial nitric oxide synthase (eNOS) was done in rat kidneys. Fenofibrate was administered for 1 week before subjecting rats to AKI. In separate group, the nitric oxide synthase inhibitor, L-nitroarginine methyl ester (L-NAME) was administered prior to fenofibrate treatment. In I/R group, significant alteration in the serum/urine parameters indicated AKI and hepatic dysfunction along with marked increase in kidney and liver injury scores. Treatment with fenofibrate attenuated AKI and associated hepatic dysfunction. Moreover, I/R-induced decrease in renal eNOS expression was abrogated by fenofibrate. Pre-treatment with L-NAME abolished fenofibrate mediated reno- and hepato-protective effects. In conclusion, fenofibrate attenuates I/R-induced AKI and associated hepatic dysfunction putatively through modulation of eNOS expression.

Ameliorative role of bosentan, an endothelin receptor antagonist, against sodium arsenite-induced renal dysfunction in rats.

Arsenic exposure is well documented to cause serious health hazards, such as cardiovascular abnormalities, neurotoxicity and nephrotoxicity. In the present study, we intended to explore the role of bosentan, an endothelial receptor antagonist, against sodium arsenite-induced nephrotoxicity and hepatotoxicity in rats. Sodium arsenite (5 mg/kg, oral) was administered for 4 weeks to induce renal dysfunction in rats. Sodium arsenite intoxicated rats were treated with bosentan (50 and 100 mg/kg, oral) for 4 weeks. Arsenic led renal damage was demonstrated by significant increase in serum creatinine, urea, uric acid, potassium, fractional excretion of sodium, microproteinuria and decreased creatinine clearance in rats. Sodium arsenite resulted in marked oxidative stress in rat kidneys as indicated by profound increase in lipid peroxides, and superoxide anion generation alongwith decrease in reduced glutathione levels. Hydroxyproline assay highlighted arsenic-induced renal fibrosis in rats. Hematoxylin-eosin staining indicated glomerular and tubular changes in rat kidneys. Picrosirius red staining highlighted collagen deposition in renal tissues of arsenic treated rats. Immunohistological results demonstrated the reduction of renal eNOS expression in arsenic treated rats. Notably, treatment with bosentan attenuated arsenic-induced renal damage and resisted arsenic-led reduction in renal eNOS expression. In addition, sodium arsenite-induced alteration in hepatic parameters (serum aspartate aminotransferase, alanine transferase, alkaline phosphatase, bilirubin), oxidative stress and histological changes were abrogated by bosentan treatment in rats. Hence, we conclude that bosentan treatment attenuated sodium arsenite-induced oxidative stress, fibrosis and reduction in renal eNOS expression in rat kidneys. Moreover, bosentan abrogated arsenic led hepatic changes in rats.

Long-term exposure to copper induces autophagy and apoptosis through oxidative stress in rat kidneys.

Copper (Cu) is an essential trace element for most organisms. However, excessive Cu can be highly toxic. The purpose of this study was to elucidate the mechanism underlying Cu toxicity in the kidneys of rats after treatment with CuCl2 (15 [control], 30, 60, or 120mg/kg in the diet) for 180 days. Histological and ultrastructural changes, antioxidant enzyme activity, and the mRNA and protein levels of apoptosis and autophagy-related genes were measured. The results showed that Cu exposure led to significant accumulation of copper in kidneys and disorganized kidney morphology. The activities of total anti-oxidation capacity (T-AOC) and superoxide dismutase (SOD) in the kidneys decreased significantly, while the malondialdehyde (MDA) content increased. Furthermore, excessive Cu markedly upregulated the expression of autophagy and apoptosis-related genes (LC3A, LC3B, ATG-5, Beclin-1, Caspase3, CytC, P53, Bax), but downregulated the expression of P62, mTOR and BCL-2. Moreover, the LC3B/LC3A, ATG-5, Beclin-1, P53, Caspase3 proteins were up-regulated while P62 was down-regulated in the kidney tissues of the treatment groups. Overall, these findings provide strong evidence that excess Cu can trigger autophagy and apoptosis via the mitochondrial pathway by inducing oxidative stress in rat kidneys.

Rat Böbrek Dokusunda Kurşunun Neden Olduğu Oksidatif Strese Karşı Kitosanın Koruyucu etkisi

Kitosan antioksidan ve şelatör özelliğe sahip doğal bir polimerdir. Bu çalışmada kurşun toksikosyonu oluşturulmuş ratların böbrek dokusu kurşun (Pb), molandialdehit (MDA), 8-hidroksi deoksiguanozin (8-OHdG), glutatyon (GSH), seroloplazmin konsantrasyonu ve katalaz aktivitesi üzerine kitosanın etkisi araştırıldı. Her grupta sekiz adet olacak şekilde 28 adet erkek Wistar albino rat, kontrol (C), kurşun grubu (Pb grubu), kurşun+kitosan (Pb+CS grubu) ve kitosan (CS grubu) olmak üzere dört gruba ayrıldı. Kurşun grubuna 5 gün, 50 mg/kg kurşun asetat intraperitonel (ip) ve kitosan gruplarına (CS+Pb ve CS grupları) 28 gün boyunca 200 mg/kg kitosan gavaj yoluyla uygulandı. Çalışma sonunda, kurşun, MDA, 8-OHdG, seruloplazmin, GSH konsantrasyonu ve katalaz aktivitesi böbrek dokusunda ölçüldü. Kontrol grubu ile karşılaştırıldığında, Pb uygulanan gruplarda böbrek dokusunda Pb, MDA, 8-OHdG ve seruloplazmin seviyesi arttı, GSH seviyesi ile katalaz aktivitesi ise azaldı (p&amp;lt;0.05). Kurşun ile birlikte kitosan verilmesi böbrek dokusunda Pb, MDA ve seruloplazmin seviyelerini azalttı, CAT aktivitesini arttırdı (p&amp;lt;0.05). GSH ve 8-OHdG seviyelerinde önemli değişiklik olmadı (p&amp;gt;0.05). Elde edilen sonuçlar, kitosanın, kurşun uygulaması oluşan oksidatif streseten böbreği koruduğunu göstermektedir.Her grupta sekiz adet olacak şekilde 28 adet male Wistar albino rat control (C), lead group (Pb group), lead+ chitosan (Pb+CS group) ve chitosan (CS group) olmak üzere dört gruba ayrıldı. Lead group were administered 50 mg/kg lead acetate intraperitoneal (ip) for 5 days and chitosan groups (CS+Pb and CS groups) were adminestered 200 mg/kg chitosan for 28 days via gavage. At the end the study, lead, MDA, 8-OHdG, seruloplazmin, GSH konsantrasyonu ve katalaz aktivitesi böbrek dokusunda ölçüldü.Kontrol grubu ile karşılaştırıldığında, Pb uygulanan gruplarda böbrek dokusunda Pb, MDA, 8-OHdG ve seruloplazmin seviyesi arttı, GSH seviyesi ile katalaz aktivitesi ise azaldı (p&amp;lt;0.05). Kurşun ile birlikte kitosan verilmesi böbrek dokusunda Pb, MDA ve seruloplazmin seviyelerini azalttı, CAT aktivitesini arttırdı (p&amp;lt;0.05). GSH ve 8-OHdG seviyelerinde önemli değişiklik olmadı (p&amp;gt;0.05). Elde edilen sonuçlar, kitosanın, kurşun uygulaması oluşan oksidatif streseten böbreği koruduğunu göstermektedir.

Amelioration of DENA-induced oxidative stress in rat kidney and brain by the essential oil of Elettaria cardamomum

The goal of the present work was to study the protective role of the essential oil of Elettaria cardamomum (cardamom) against diethylnitrosamine (DENA)-induced oxidative stress in the kidney and brain of rats in comparison with geraniol, a pure compound as one of the main components of cardamom essential oil. Geraniol or cardamom essential oil was orally administered every day (100 and 200 mg/kg) for 1 week before DENA administration and continuously administered for 26 weeks. The levels of brain and kidney ornithine decarboxylase (ODC), brain acetylcholinesterase (AChE) and renal markers such as urea and creatinine were elevated after DENA administration. However, cardamom and geraniol administration decreased kidney and brain oxidative stress and lowered the activity of ODC in brain and kidney and the activity of AChE in brain. Cardamom or geraniol had significantly reduced the level of lipid peroxidation to almost half the value in DENA group and enhanced glutathione level by double its values in brain and kidney compared to glutathione levels in DENA treated-rats. In addition, geraniol or oil of cardamom improved the activities of the antioxidant markers; catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S transferase in the brain and kidneys of DENA-treated rats. The results support the chemopreventive, antioxidant, neuroprotective and anticancer effects of the essential oil of cardamom, which are mediated through its inhibition of ODC and AChE activities and activation of antioxidant markers.

Mechanism of valproic acid-induced Fanconi syndrome involves mitochondrial dysfunction and oxidative stress in rat kidney.

Drug-induced kidney proximal tubular injury and renal failure (Fanconi syndrome; FS) is a clinical complication. Valproic acid (VPA) is among the FS-inducing drugs. The current investigation was designed to evaluate the role of mitochondrial dysfunction and oxidative stress in VPA-induced renal injury. Animals received VPA (250 and 500mg/kg, i.p., 15 consecutive days). Serum biomarkers of kidney injury and markers of oxidative stress were assessed. Moreover, kidney mitochondria were isolated and mitochondrial indices, including succinate dehydrogenase activity (SDA), mitochondrial depolarization, mitochondrial permeability transition pore (MPP), reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial glutathione, and ATP were determined. Valproic acid-treated animals developed biochemical evidence of FS as judged by elevated serum gamma-glutamyl transferase (γ-GT), alkaline phosphatase (ALP), creatinine (Cr), and blood urea nitrogen (BUN) along with hypokalaemia, hypophosphataemia, and a decrease in serum uric acid. VPA caused an increase in kidney ROS and LPO. Renal GSH reservoirs were depleted and tissue antioxidant capacity decreased in VPA-treated animals. Renal tubular interstitial nephritis, tissue necrosis, and atrophy were also evident in VPA-treated rats. Mitochondrial parameters including SDA, MMP, GSH, ATP and MPP were decreased and mitochondrial ROS and LPO were increased with VPA treatment. It was found that carnitine (100mg/kg, i.p.) mitigated VPA adverse effects towards the kidney. These data suggest that mitochondrial dysfunction and oxidative stress contributed to the VPA-induced FS. On the other hand, carnitine could be considered a potentially safe and effective therapeutic option in attenuating VPA-induced renal injury.

Carvacrol attenuates cyclophosphamide-induced oxidative stress in rat kidney.

Cyclophosphamide (CP) is an antineoplastic drug that induces kidney damage via producing oxidative stress. Carvacrol (CAR) has antioxidative effect and we postulated that it can be protective against CP-induced nephrotoxicity. Six groups (n = 7) of rats (control, 100 mg/kg CP, CP+5 mg/kg CAR, CP+10 mg/kg CAR, 5 mg/kg CAR, and 10 mg/kg CAR) were injected intraperitoneally. Serum malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), creatinine (CRE), total antioxidant capacity (TAC), and total oxidant state (TOS) were measured, and oxidative stress indexes (OSI) were calculated. Kidneys were also analyzed histologically. In CP-alone group MDA, CRE, TOS, and OSI levels increased whereas GSH, SOD, CAT, and TAC levels decreased compared with control group. In CP plus CAR groups, MDA, TOS, and OSI levels decreased whereas GSH, SOD, CAT, and TAC levels increased compared with CP-alone group. However, CRE levels were similar in CP-alone and CP+5 CAR group whereas decreased in CP+10 CAR group. CP+10 CAR group was significantly different in all parameters (except TAC) from CP+5 CAR group. Kidney microscopy was showed lower tissue damage in CP plus CAR groups. In conclusion, 10 mg/kg CAR is more effective than 5 mg/kg CAR in prevention of CP-induced oxidative damage on kidney.

GSPE reduces lead-induced oxidative stress by activating the Nrf2 pathway and suppressing miR153 and GSK-3β in rat kidney.

Lead (Pb) is a global environmental health hazard that leads to nephrotoxicity. However, the effective treatment of Pb-induced nephrotoxicity remains elusive. Grape seed procyanidin extract (GSPE) has beneficial properties for multiple biological functions. Therefore, the present study investigated whether GSPE reduced Pb-induced nephrotoxicity as well as the protective mechanism of GSPE in a well-established 35-day Pb induced nephrotoxicity rat model. The results showed that GSPE normalized Pb-induced oxidative stress, histological damage, inflammatory, apoptosis, and changes of miR153 and glycogen synthase kinase 3β (GSK-3β) levels in rat kidney. Moreover, GSPE enhanced the induction of phase II detoxifying enzymes (heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1) by increasing nuclear factor-erythroid-2-related factor 2 (Nrf2) expression. This study identifies for the first time that Pb-induced oxidative stress in rat kidney is attenuated by GSPE treatment via activating Nrf2 signaling pathway and suppressing miR153 and GSK-3β. Nrf2 signaling provides a new therapeutic target for renal injury induced by Pb, and GSPE could be a potential natural agent to protect against Pb-induced nephrotoxicity.

Protective effect of Nigella sativa oil on cisplatin induced nephrotoxicity and oxidative damage in rat kidney

BackgroundNephrotoxicity is a severe complication in patients undergoing cisplatin (CP) chemotherapy. Previous studies in our lab have shown that administration of a single dose of CP results in decrease in the activities of brush border membrane (BBM) and free radical scavenging enzymes and induces oxidative stress in rat kidney. Nigella sativa, is one of the most revered medicinal plant known for its numerous health benefits. Nigella sativa seed/oil has been shown to improve kidney functions in animal models of acute kidney injury. ObjectiveThe present study was undertaken to investigate whether Nigella sativa oil (NSO) can prevent the CP-induced nephrotoxic effects. ResultsThe effect of NSO was determined on CP induced alterations in various serum parameters and on enzymes of carbohydrate metabolism, BBM and antioxidant defense system in renal cortex and medulla. Administration of NSO (2ml/kg bwt. orally), prior to and following a single dose CP treatment (6mg/kg bwt. i.p), significantly attenuated the CP induced increase in serum creatinine (Scr) and blood urea nitrogen (BUN) and decrease in the activities of BBM enzymes in renal cortical and medullary homogenates as well as in isolated BBM vesicles (BBMV). NSO administration also precluded CP induced alterations in the activities of carbohydrate metabolism enzymes and in the enzymatic and non-enzymatic antioxidant parameters. Histopathological observations showed extensive kidney damage in CP treated animals and remarkably reduced renal injury in CP and NSO co-treated group. ConclusionThe biochemical and histological data suggest a protective effect of NSO against CP-induced acute kidney injury.

Simvastatin attenuates chromium-induced nephrotoxicity in rats.

BackgroundHexavalent Chromium (Cr (VI)) compounds are extremely toxic and have been demonstrated to induce nephrotoxicity associated with oxidative stress in humans and animals. The wide environmental distribution of these agents lead to an increase interest of preventive effects of its adverse effects. ObjectivesThe propose of the present study was to determine the potential protective effects of simvastatin (SIMV) on Cr (VI)-induced nephrotoxicity in rat. Materials and MethodsForty-eight adult male Wistar rats (180-220 g BW) were randomly assigned to eight groups (n = 6). Group one received SIMV 20 mg/kg/day. Group two was given vehicle only. Groups three, five and seven received intraperitoneally (i.p) sodium dichromate (Cr (VI)) at doses of 8, 12 and 16 mg/kg body weight. Groups four, six and eight pretreated with the 20 mg/kg SIMV 30 minutes to prior administration of Cr (VI) at doses of 8, 12 and 16 mg/kg, respectively. The experiment repeated for eight consecutive days. Twenty-four hours after the last administration, animals were killed with overdose of sodium pentobarbital. Kidney tissues were excised for measuring malondialdehyde (MDA), glutathione (GSH) and histopathological examination. ResultsChromium induced a dose dependent elevation of MDA and reduction of GSH levels. Histopathological manifestations were observed in Cr (VI)-treated rats. SIMV administration restored Cr (VI) produced biochemical and morphological changes in rat kidney. SIMV decreased MDA values and increased GSH levels in Cr (VI)-treated rats. SIMV clearly reversed the microscopic damage, demonstrating its protective effects against Cr (VI)-induced kidney injury. ConclusionsThis observation suggests that SIMV may have a protective effect against Cr (VI)-induced oxidative stress in rat kidney.