Kidney Glutathione Research Articles

Cinnamon Aqueous Extract Attenuates Diclofenac Sodium and Oxytetracycline Mediated Hepato-Renal Toxicity and Modulates Oxidative Stress, Cell Apoptosis, and Inflammation in Male Albino Rats.

Among commonly consumed anti-inflammatory and antimicrobial drugs are diclofenac sodium (DFS) and oxytetracycline (OTC), especially in developing countries because they are highly effective and cheap. However, the concomitant administration of anti-inflammatory drugs with antibiotics may exaggerate massive toxic effects on many organs. Cinnamon (Cinnamomum zeylanicum, Cin) is considered one of the most broadly utilized plants with various antioxidant and anti-inflammatory actions. This study aimed to evaluate the possible protective effects of cinnamon aqueous extract (Cin) against DFS and OTC hepato-renal toxicity. Eight groups (8/group) of adult male albino rats were treated orally for 15 days with physiological saline (control), Cin aqueous extract (300 mg/kg b.w.), OTC (200 mg/kg b.w.), single dose of DFS at the 14th day (100 mg/kg b.w.), DFS + OTC, Cin + DFS, Cin + OTC, and Cin + DFS + OTC. The administration of DFS and/or OTC significantly increased (p < 0.05) the serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea, creatinine, and uric acid. Serum levels of pro-inflammatory cytokines, as well as hepatic and renal malondialdehyde and nitric oxide metabolites, were also raised following DFS and OTC administration. Meanwhile, the activities of reduced glutathione, superoxide dismutase, and catalase in liver and kidney were significantly suppressed in DFS, OTC, and DFS + OTC treated rats. Moreover, hepatic and renal tissue sections from these rats exhibited overexpression of caspase-3 and cyclooxygenase-II on immunohistochemical investigation. The administration of Cin aqueous extract ameliorated the aforementioned deteriorations caused by DFS, OTC, and their combination. Conclusively, Cin is a promising protective plant extract capable of attenuating the oxidative damage, apoptosis, and inflammation induced by DFS and OTC either alone or combined, on hepatic and renal tissues.

Safety assessment of oral administration of ethanol extract of Justicia carnea leaf in healthy wistar rats: hematology, antioxidative and histology studies

BackgroundConsumption of medicinal plants has diverse therapeutic benefits and could also have toxic effect. Justicia carnea is a medicinal plant that is used conventionally as blood tonic from time immemorial in Nigeria. The aim of this study is to evaluate the safety of ethanol extract of J. carnea leaf assessing the hematology indices, organ antioxidant system and histology in healthy male wistar rats.MethodsPowdered sample was extracted using absolute ethanol and concentrated to obtain a slurry paste of J. carnea ethanol extracts. Acute toxicity was determined in two phases using Lorke method. In subacute study, rats were randomized into six groups of five rats per group: Group 1 (control) received distilled water, group 2, 3, 4, 5, 6 received 50, 100, 500, 800 and 1200 mg/kg body weight of J. carnea ethanol extract once daily using oral gavage. At the end of 14th day of administration, rats were allowed to fast overnight, sacrificed to collect samples for biochemical analysis and histopathological examination.ResultsThe LD50 of extract was greater than 5000 mg/kg body weight. Higher doses (> 500 mg/kg) of extract significantly (p < 0.05) increased RBC, hemoglobin and platelet compared to the control. Liver superoxide dismutase (SOD) activity was significantly (p < 0.05) increased at 1200 mg/kg while other tested doses caused no detrimental effect on glutathione, catalase, SOD and malondialdehyde level in liver and kidney. Histopathological examination of liver and kidney showed mild to severe pathological lesion in a dose dependent manner.ConclusionsThe results of this study suggests that ethanol extract of J. carnea leaf is relatively safe, could be beneficial in alleviating hematology related abnormalities without causing adverse effects on endogenous antioxidant system. However, caution should be taken as higher dose at 1200 mg/kg could cause noticeable tissue injury.

Anethole Dithiolethione Increases Glutathione in Kidney by Inhibiting γ-Glutamyltranspeptidase: Biochemical Interpretation and Pharmacological Consequences.

Aims Anethole dithiolethione (ADT) is a marketed drug to treat xerostomia. Its mechanism of action is still unknown, but several preclinical studies indicate that it is able to increase intracellular glutathione (GSH) and protect against oxidative stress. Here, we investigated the molecular mechanisms behind these effects. Results Oral treatment of rats confirmed the GSH enhancing properties of ADT; among the different organs examined in this study, only the kidney showed a significant GSH increase that was already observed at low-dose treatments. The increase in GSH correlated with a decrease in γ-glutamyltranspeptidase (γ-GT) activity of the different tissues. In vitro and ex vivo experiments with tubular renal cells and isolated perfused rat kidney showed that the cellular uptake of intact GSH was correlated with the extracellular concentrations of GSH. Conclusions. The prominent in vivopharmacological effect of ADT was a marked increase of GSH concentration in the kidney and a decrease of some systemic and renal biomarkers of oxidative stress. In particular, by inhibition of γ-GT activity, it decreased the production cysteinylglycine, a thiol that has prooxidant effects as the consequence of its autooxidation. The activity of ADT as GSH enhancer in both the circulation and the kidney was long-lasting. All these characteristics make ADT a promising drug to protect the kidney, and in particular proximal tubule cells, from xenobiotic-induced damage.

Florfenicol causes excessive lipid peroxidation and apoptosis induced renal injury in broilers

In order to study the effects and mechanism of florfenicol (FFC) on the kidney function of broilers, 180 1-day-old broilers were randomly divided into 6 groups, 30 in each group. Except for the control group, different doses of FFC were added to drinking water in the other 5 groups (0.15 g/L, 0.3 g/L, 0.6 g/L, 1.2 g/L and 1.8 g/L). After continuous administration for 5 days, renal histopathological changes, serum renal function indicators, renal peroxidation products and antioxidant factors, and apoptotic factors were detected in broilers aged 21 and 42 days. The results showed that compared with the control group, the kidney tissue structure was disordered, the glomerulus was atrophic, the cystic cavity was enlarged, and the epithelial cells of renal tubules were seriously vacuolated in broilers of treatment groups. And with the growth of broilers, the kidney injury of broilers in the low-dose FFC group was relieved. FFC significantly increased the contents of uric acid (UA), blood urea nitrogen (BUN), creatinine (CRE) in serum and malondialdehyde (MDA) in kidney of broilers, but significantly reduced the levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in kidney. FFC significantly inhibited the mRNA relative transcriptional levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase-1 (NQO-1), and increased the mRNA and protein expression levels of p53, Caspase-3 and Caspase-6 in kidney tissue of broilers. It is concluded that FFC has certain nephrotoxicity to broilers, and its effect on kidney is dose-dependent and reversible. FFC causes intense lipid peroxidation in broiler kidney by inhibiting the expression of related factors in the downstream signal pathway of Nrf2. FFC can also up-regulate the expression of pro-apoptotic factors and accelerate the abnormal apoptosis of renal cells, thus seriously affecting the renal function of broilers.

Ibrolipim attenuates early-stage nephropathy in diet-induced diabetic minipigs: Focus on oxidative stress and fibrogenesis

It is well-recognized that hyperlipidemia and lipid peroxidation contribute to the progression of diabetic nephropathy (DN), which is associated with oxidative stress (OS) and fibrotic lesions. Ibrolipim, a specific lipoprotein lipase activator, has been proved to reduce hyperglycemia and hyperlipidemia, suppress renal lipid deposition, and also protect renal damage. However, the underlying mechanisms of its renoprotective effect are not clearly elaborated. Herein, the present study was to identify whether the putative mechanism of Ibrolipim was related to OS and fibrogenesis in diabetic minipigs fed by high-sucrose and high-fat diet (HSFD) with or without Ibrolipim for 5 months. Compared with the normal control diet, nutrient stress induced by HSFD caused moderate glomerulosclerosis and tubulointerstitial fibrosis, and promoted renal ultrastructural and functional abnormalities. These abnormalities were correlated with renal OS and fibrogenesis characterized by the increased levels of reactive oxygen species (ROS), malondialdehyde, hydroxyproline, collagen type Ⅳ alpha 1 and fibronectin, and decreased contents of reduced glutathione and total antioxidant capacity in kidneys. Ibrolipim significantly ameliorated these abnormalities in HSFD-fed minipigs. In addition, Ibrolipim diminished HSFD-induced nicotinamide-adenine dinucleotide phosphate oxidase-4 activation to reduce ROS production, and enhanced the expression and activity of antioxidant enzymes (i.e. superoxide dismutase 1, catalase and glutathione peroxidase 1) to increase ROS elimination, resulting in obvious suppression of renal OS. Meanwhile, Ibrolipim not only inhibited the upregulation of transforming growth factor-β1 but also partially reversed the downregulation of matrix metalloproteinase 2, and then prevented extracellular matrix (ECM) accumulation. Taken together, Ibrolipim exhibits anti-oxidative and anti-fibrotic effects via modulating the rebalance of renal ROS and ECM metabolism, and ultimately attenuates the progression of nephropathy in diet-induced diabetic minipigs.

Manganese-Induced Nephrotoxicity Is Mediated through Oxidative Stress and Mitochondrial Impairment

Manganese (Mn) is an essential element that is incorporated in various metabolic pathways and enzyme structures. On the other hand, a range of adverse effects has been described in association with Mn overexposure. Mn is a well-known neurotoxic agent in mammals. Renal injury is another adverse effect associated with Mn intoxication. No precise mechanism for Mn nephrotoxicity has been identified so far. The current study was designed to evaluate the potential mechanisms of Mn-induced renal injury. Rats were treated with Mn (20 and 40 mg/mL, respectively, in drinking water) for 30 consecutive days. Markers of oxidative stress, as well as several mitochondrial indices, were assessed in the kidney tissue. Renal injury was evident in Mn-treated animals, as judged by a significant increase in serum BUN and creatinine. Moreover, urinalysis revealed a significant increase in urine glucose, phosphate, and protein in Mn-treated rats. Kidney histopathological alterations, including tubular atrophy, interstitial inflammation, and necrosis, were also detected in Mn-treated animals. Biomarkers of oxidative stress, including an increment in reactive oxygen species (ROS), lipid peroxidation, and oxidized glutathione (GSSG), were detected in Mn-treated groups. On the other hand, kidney glutathione (GSH) stores and total antioxidant capacity were depleted in Mn groups. Mn exposure was associated with significant mitochondrial depolarization, decreased mitochondrial dehydrogenases activity, mitochondrial permeabilization, and depletion of adenosine tri-phosphate (ATP) content. These data highlight oxidative stress and mitochondrial impairment as potential mechanisms involved in Mn-induced renal injury.

Dietary selenium required to achieve body homeostasis and attenuate pro-inflammatory responses in Atlantic salmon post-smolt exceeds the present EU legal limit

Selenium (Se) supplementation either as inorganic or organic form was evaluated in Atlantic salmon post-smolt in vivo and in vitro. The basal diet was formulated to be low in fish meal and contain 0.24 mg Se kg−1; six other diets with Se inclusion of 0.15, 0.4, 0.7 or 1.1 mg kg−1 as sodium selenite (SS) and 0.15 or 0.4 mg kg−1 as L-selenomethionine (SM) were formulated from the basal diet. The diets were fed to Atlantic salmon post-smolt (mean initial weight, 216 ± 27 g) in triplicate groups (35 fish tank−1) and reared in flow-through seawater (33 ppt) at 10–12 °C for 9 weeks. At the end of the feeding trial, whole fish and tissues were sampled for in vivo assessment; whereas, liver cells and head kidney leukocytes (HKL) were isolated and their primary cultures used for in vitro assessment following exposure to hydrogen peroxide (H2O2), lipopolysaccharide (LPS) or poly I:C (PIC). Growth, feed intake, feed conversion ratio, specific growth rate, hepato-somatic index, proximate composition and mineral concentration of the whole fish (except for Se) were unaffected by dietary Se (p > .05). Hematocrit was significantly higher in fish fed the 0.4 mg Se supplemented feeds, irrespective of the Se source (p = .02). The Se concentration in whole body, liver, muscle, plasma, kidney and liver/kidney Se ratio increased with increasing dietary Se concentration (p < .0001). Level of oxidised glutathione (GSSG) in liver and head kidney followed a quadratic function (p < .05) indicating that the concentrations were lower at intermediate SS supplementation of 0.4 and 0.65 mg Se kg−1 (total Se, 0.65 and 0.87 mg Se kg−1). Impact of Se sources on glutathione redox status was similar. Slope-ratio analysis revealed SM to be more efficient than SS in improving apparent availability, whole body or tissues Se status, Se retention and reducing Se loss to the environment. In vitro, the mRNA expression of p38mapk and aif, in liver cells were affected by the impact of dietary Se, but not by the treatment of H2O2 (p < .05). In the HKL, the LPS and PIC induced pro-inflamatory action of il-1β, cox2, nfkβ and viperin were attenuated by SM supplementation, but not by SS (p < .001). Dietary Se supplementation required to the basal diet containing 0.24 mg Se kg−1 was 0.41 mg Se as SS (total 0.65 mg kg−1) or 0.17 mg Se as SM (total 0.41 mg kg−1) based on body Se homeostasis or tissue Se status. SM inclusion at 0.4 mg kg−1 diet (total, 0.65 mg kg−1) attenuated LPS or PIC induced pro-inflammatory responses in vitro. Overall, Se requirement of Atlantic salmon post smolt was 0.27 mg kg−1 diet, on availale basis. Dietary Se level required to maintain body Se homeostasis and improved health status of Atlantic salmon fed plant-based diets (0.65 mg kg−1 diet) exceed the existing EU maximum limit of 0.5 mg Se kg−1 diet. SM as the Se source in salmon feeds has the potential to improve salmon health and reduce Se emissions from Norwegan salmon farming by 60 to 70%.

Attenuation of Paraquat-Induced Nephrotoxicity and Dysfunction in Male Wistar Albino Rats

Background. Paraquat (PQ) is a pesticide commonly used in the control of weed in agricultural practices worldwide. Exposure to PQ has adverse biochemical and physiological consequences to humans and animals. The mechanism of toxicity is linked to the generation of reactive oxygen species and subsequent lipid peroxidation. Presently, no single effective antidote to PQ toxicity has been established. Therefore, the need to continually investigate different treatment approaches is of paramount importance. Objective. This study evaluated the capacity of selected dietary supplements to attenuate paraquat-induced kidney dysfunction and damages by determining some kidney function biomarkers and oxidative parameters. Methods. Thirty-six Wistar albino rats were randomly separated into six groups. Each group (except Normal control) was intoxicated every other day with 1.5 mg/kg body weight of PQ and four groups (except PQ and Normal control groups) were treated daily with 40 mg/kg of garlic, glutathione and vitamin C for two weeks. Results. The results showed significant ( p < 0.05) increases in concentration of kidney malondialdehyde, urea, creatinine, and blood lipid profiles. Also, significant decrease in concentrations of high-density lipoprotein cholesterol, kidney glutathione and total antioxidant capacity were presented by PQ control group compared to other PQ exposed groups treated with the antioxidant compounds. Conclusions. PQ-induced changes indicated kidney dysfunction and damage. However, the administration of antioxidant supplements attenuated the PQ-induced biochemical and physiological dysfunction in the rats.

Launaea taraxacifolia leaf partitions ameliorate alloxan-induced pathophysiological complications via antioxidant mechanisms in diabetic rats

Launaea taraxacifolia (Wild.) Amin ex. Jeffery belongs to family Asteracaea. The plant is used for treatment of diseases and eaten as vegetable in Nigeria. This study investigated the ameliorative potentials of L. taraxacifolia leaf partitions in alloxan induced diabetic complications. Male Albino rats were divided into eleven groups of five rats each. Diabetes was induced following intraperitoneal administration of 150 mg/kg alloxan monohydrate and was treated with 200 and 300 mg/kg of each partitioned fractions. Hyperglycemia was reversed in all treated rats within seven days of treatments. Rats treated with the partitions showed significant increase in hematological parameters compared with diabetic control. N-hexane fraction had the best overall effect against oxidative stress particularly on heart and pancreas reduced glutathione (GSH), superoxide dismutase (SOD) and kidney glutathione S-transferase (GST) activities. The various degrees of degeneration observed in the kidney, liver, pancreas and heart of the untreated diabetic rats were milder in rats treated with partitions. The results therefore revealed the ameliorative potentials of the partitioned fractions of L. taraxacifolia leaf extract against diabetes mellitus complications via activation of the antioxidant enzymes.

Study on lipid peroxidation and In vivo antioxidant activity of various extract of Dyschoriste littoralis nees on paracetamol-induced hepatotoxicity rats

The current investigation was to examine the antioxidant potential of D.littoralis Nees. (family Acanthaceae) On paracetamol-induced hepatotoxicity in rats. The aerial parts of D.littoralis Nees. The powder was concentratesed with various solvents (PE, EA, and methanol) through Soxhlet concentrates and various crude concentrates utilized for hepatoprotective activity. Hepatotoxicity was induced by paracetamol (2g/kg b.wt.) on the 5th day of the investigational period and given orally. Paracetamol-induced rats to exhibit elevated activities of TBARS and reduction the enzymes levels such as Superoxide dismutase(SOD), catalase(CAD), Glutathione peroxidise (GPx), Glutathione S transferase(GST) and Glutathione (GSH) in liver and kidney. Furthermore, Oral administration of the ethyl acetate concentrates of D.littoralis (200 mg/ kgb.wt.) given rats were major reduction the level of TBARS and also significantly elevated the levels of the enzyme such as Superoxide dismutase(SOD), catalase(CAD), Glutathione peroxidise(GPx), Glutathione S transferase(GST) and Glutathione (GSH) in liver and kidney as compared to other concentrates. Thus, results suggested that ethyl acetate concentrates of D.littoralis could be afford better antioxidant effect against paracetamol-induced hepatotoxicity rats.

EXPLORATION OF PROTECTIVE EFFECT OF HYDROALCOHOLIC EXTRACT OF ALSTONIA SCHOLARIS BARK IN STZ-INDUCED EARLY DIABETIC NEPHROPATHY MODEL IN RATS

Alstonia scholaris (fam. Apocynaceae) is an indigenous plant used traditionally for the treatment of diabetes and associated complications. However the nephroprotective potential of the plant is not scientifically evaluated. Objective of the present was to investigate renal protective activity of hydroalcoholic extract of A. scholaris bark (HEAS) in streptozotocin (STZ)-induced early diabetic nephropathy in rats and to focus on its possible mechanism of action. Experimental diabetes was induced in Wistar rats using single intraperitoneal injection of streptozotocin (65 mg/kg). Animals were divided in five groups (n=6) and treated with 150 mg/kg and 300 mg/kg HEAS for 4 weeks. At the end of study period, fasting blood glucose, blood urea nitrogen (BUN), serum creatinine, total proteins, serum albumin, serum insulin and glycosylated haemoglobin, superoxide dismutase, catalase, reduced glutathione and MDA in kidney were evaluated. Urine was analyzed for albumin, total proteins and creatinine clearance. Kidney and pancreas were subjected for histopathology. Significant decrease in fasting blood glucose, creatinine, albumin, BUN, total proteins and urinary total proteins was observed. Significant improvement in serum insulin, glycosylated Hb, oxidative stress parameters of kidney including superoxide dismutase, catalase and reduced glutathione has been observed in HEAS treated diabetic rats. Histopathology of kidney and pancreatic tissues showed structural improvement. Present study has revealed that HEAS prevented the progression of diabetic nephropathy in STZ-diabetic rats by improving the disturbed glucose homeostasis and by amelioration of renal oxidative stress.

Ameliorating efficacy of eugenol against metanil yellow induced toxicity in albino Wistar rats

Metanil yellow, an azo dye, is a non-permitted synthetic food colour used extensively in India and other developing countries as food additive. Present communication reports the toxic effects of metanil yellow on hepatic and kidney tissues and its amelioration by eugenol, vitamin E and vitamin C. Oral administration of metanil yellow in albino Wistar rats for 28 days caused elevation in serum enzymes (glutamate oxaloacetate transaminase, gluatamate pyruvate transaminase, alkaline phosphatase), and total bilirubin along with decline in albumin and total protein levels. At tissue level, activities of oxidative stress markers viz., superoxide dismutase, catalase and reduced glutathione in liver and kidney were reduced to about half while malondialdehyde level increased significantly under the influence of metanil yellow. Co-administration of eugenol/vitamin E/vitamin C in metanil yellow intoxicated rats exhibited considerable restoration of oxidative stress as well as hepatic and renal function markers in serum and tissues. The study revealed that eugenol has antioxidant, hepatoprotective and renoprotective activities.

Study of Acute Toxicity and the Effect of the Aqueous Extract of a Formulation of Three Edibles Mushrooms on Oxidative Stress Induced in Rats

Edible mushrooms, especially <i>Pleurotus spp</i>. contain a wide variety of biomolecules that can play a protective role against oxidative damage. We investigate the effect of formulation of the aqueous extract of three edibles mushrooms commonly consumed in Cameroon on oxidative stress induced in rats induced by lead acetate: <i>Pleurotus pulmonarius</i>, <i>Pleurotus floridanus</i> and <i>Pleurotus sajor-caju</i>. The formulation made of the three species (1w:1w:1w) were dissolved in distilled water for acute toxicity (at 2000 mg/kg of bw) and protective effect (at 400 mg/kg of bw for 21 days) against oxidative stress induced in vivo with lead acetate (35 mg/kg of bw for 3 days). Several parameters were investigated in the serum and organs homogenous such as lipid profile, hepatic and oxidative stress markers. No particular sign of toxicity of the extract were revealed. After lead administration, significant increases were found in serum transaminases activity, creatinine, and lipid profile associated with a decrease of serum protein content and High Density Lipoprotein. In addition, significant increase in lipid peroxidation expressed as the concentration of malondialdehyde (MDA) and decreased level of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activities in serum, liver and kidney showed oxidative stress due to lead exposure. The pre-treatment with aqueous extract of the mushroom’s formulation showed protective effects against lead induced hepato-renal damage by improving antioxidant parameters, as well as ascorbic acid used as a reference. In conclusion, these mushrooms may be used as a natural source of antioxidants for food supplements against oxidative stress.

Protective effects of bark ethanolic extract from Spondias dulcis Forst F. against DNA damage induced by benzo[a]pyrene and cyclophosphamide.

This study evaluated the genotoxicity, mutagenicity, antigenotoxicity, and antimutagenicity effects on biochemical parameters of oxidative stress of the Spondias dulcis bark ethanolic extract on mice. The extract was evaluated in the doses of 500, 1000, and 1500 mg/kg bw via gavage. To evaluate the protective effects of the extract, benzo[a]pyrene (B[a]P) and cyclophosphamide (CP) were chosen as DNA damage inducers. Genotoxicity and antigenotoxicity were evaluated by the comet assay. Cytotoxicity, mutagenicity, and antimutagenicity were evaluated by the micronucleus test in bone marrow and peripheral blood. The biochemical parameters of oxidative stress were evaluated by the quantification of catalase activity (CAT) and reduced glutathione (GSH) in total blood, liver and kidney, and malondialdehyde (MDA), in liver and kidney. No genotoxic, cytotoxic, or mutagenic effect was found on mice exposed to the extract. The extract depleted the number of damaged nucleoids in total blood and the number of micronucleus (MN) in both cell types. The extract was able to increase CAT activity and GSH levels and decrease MDA levels after treatment with B[a]P and CP. The results indicate that the S. dulcis extract has potential to be used as preventive compound against DNA damage caused by CP and B[a]P.

EFFECTS OF CHROMIUM PICOLINATE ON OXIDATIVE STRESS AND HYPERGLYCEMIA IN EXPERIMENTAL TYPE 2 DIABETIC RATS

Objective: In this study, we aimed to determine the effects of chromium picolinate (CrPic) on diabetes, one of the most common and fatal diseases in the world, and its associated oxidative damages.Methods: CrPic (100 μg/kg) and metformin (1000 mg/kg) were orally administered for 21 days in rats with nicotinamide + streptozotocin-induced Type 2 diabetes.Results: Significant decreases in fasting blood glucose levels were observed 14 days after initial administration in both CrPic (p&lt;0.01) and metformin (p&lt;0.001) groups compared with a diabetic control group (DC). Malondialdehyde (MDA) levels of all tissues were significantly higher in the DC group than in a normoglycemic control group (p&lt;0.001). MDA levels of the CrPic group significantly decreased in heart (p&lt;0.05) and liver (p&lt;0.01) tissues. Glutathione (GSH) and catalase (CAT) levels in heart, kidney, and liver tissues increased in CrPic group (GSH p&lt;0.001, p&lt;0.05, and p&lt;0.01; CAT p&lt;0.001, p&lt;0.001, and p&lt;0.05, respectively). Superoxide dismutase enzyme levels significantly increased in CrPic group in the liver tissue (p&gt;0.001), but no such changes were observed in heart and kidney tissues (p&gt;0.05).Conclusion: The results obtained from this study indicate that CrPic may be effective in alleviating hyperglycemia and its consequent oxidative damage in experimental Type 2 diabetes.

A reliable LC-MS/MS method for the quantification of N-acetyl-p-benzoquinoneimine, acetaminophen glutathione and acetaminophen glucuronide in mouse plasma, liver and kidney: Method validation and application to a pharmacokinetic study.

A rapid, specific, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated to simultaneously quantify N-acetyl-p-benzoquinoneimine (NAPQI), acetaminophen-glutathione (acetaminophen-glut) and acetaminophen-glucuronide (acetaminophen-gluc) in mouse plasma, liver and kidney homogenates. Analytes were eluted by a binary gradient mobile phase composed of water (phase A) and methanol containing 0.1% formic acid (phase B) at a flow rate of 0.3 mL/min, which was performed on a CAPCELL PAK C18 MG II column. It took 3.2 min to detect three analytes in a single run. Quantification was carried out in positive mode combined with multiple reaction monitoring. The validation of the LC-MS/MS method consisted of specificity, linearity, precision, accuracy, protein precipitation recovery, matrix effect, dilution integrity and stability. The plasma and tissue homogenate calibration curves were linear over concentration ranges of 0.050-5.00, 0.050-5.00 and 0.100-40.0 μg/mL, with a lower limit of quantification of 0.050, 0.050, and 0.100 μg/mL for NAPQI, acetaminophen-glut and acetaminophen-gluc, respectively. The intra- and inter-run precision values were within 12.47% for NAPQI, 12.11% for acetaminophen-glut and 11.86% for acetaminophen-gluc at their lower limit of quantitation levels. The samples were stable under all tested conditions. This method was successfully applied to study the pharmacokinetics of NAPQI, acetaminophen-glut and acetaminophen-gluc in ICR mice following oral administration of 200 mg/kg of acetaminophen suspension.

Tempol, a superoxide dismutase mimetic agent, reduces cisplatin-induced nephrotoxicity in rats

Cisplatin (CP) is one of the most potent anti-cancer drugs used against different types of cancer. Its use is limited due to its nephrotoxicity. This study is aimed to evaluate the role of a super oxide dismutase (SOD) mimetic agent, tempol, in protection against CP nephrotoxicity in rats. Animals were divided into four groups: Group-1: Normal control group, Group-2: CP group (single dose of CP 6 mg/kg, i.p.), Group-3 and Group-4: Tempol-treated groups (50 mg/kg p.o. and 100 mg/kg p.o. respectively) daily for a week before CP injection and continued for an additional four days after CP injection. Urine and blood samples were collected for the evaluation of kidney function including serum creatinine, BUN, cystatin-c, and creatinine clearance. In addition, western blotting was used to determine urine lipocalin-2 content. Furthermore, kidney tissue was collected for the determination of oxidative stress markers, caspase-3 expression, and histopathological examination. We noticed that both doses of tempol significantly improved kidney function, which was deteriorated by CP injection. Tempol significantly elevated kidney glutathione (GSH) content and SOD activity, and decreased kidney lipid peroxidation and NOx production. Tempol also significantly decreased kidney caspase-3 expression which was elevated by CP toxicity. Thus, we conclude that tempol can protect against CP nephrotoxicity. We noticed that both doses of tempol are effective in ameliorating CP-nephrotoxicity.

Anti-arthritic properties of crude extract from Chenopodium ambrosioides L. leaves.

To evaluate the effect of hydroalcoholic crude extract (HCE) from Chenopodium ambrosioides leaves on the development of type II collagen-induced arthritis (CIA) and on pro-inflammatory cytokine balance. Collagen-induced arthritis was induced in DBA1/J mice. On the 21st day, the mice were treated orally with HCE or methotrexate, daily. Six weeks after beginning the treatment, the following measures were determined: lymphoid organs cell numbers, percentage of blood cells, IL-6, IFN-γ, TNF-α and IL-17 serum concentrations, activity of hepatic and kidney glutathione S-transferase, hepatic 7-ethoxyresorufin-O-deethylase activity, bone density and histopathology. Treatment of CIA mice with HCE 5mg/kg (HCE5) reduced the percentage of neutrophils and macrophages and the number of bone marrow cells and increased the lymphocyte numbers and the inguinal lymph node cellularity. This treatment inhibited the serum concentration of IL-6 and TNF-α, which may be related to the preservation of bone density and to the slight thickening of periarticular tissues, with minimal fibrosis and fibroblast proliferation in the joints. The CIA group presented advanced articular erosion and synovial hyperplasia. Phytochemical analysis showed mainly flavonols. HCE5 presented anti-arthritic potential and reduced IL-6 and TNF-α, which participate directly in the development and maintenance of the inflammatory process in rheumatoid arthritis.

Potential efficacy of Coenzyme Q10 against oxytetracycline-induced hepatorenal and reproductive toxicity in male rats

Therapeutic Role of Coenzyme Q10 in Brain Injury during Experimental DiabetesJihan Hussein, Dina Abo El-matty, Zakaria El-Khayat and Yasmin Abdel-Latif

Renoprotective Effects of Fermented Black Ginseng through Ameliorating Oxidative Stress Associated with Cisplatin-Induced Acute Nephrotoxicity in Mice

We aimed to evaluate the renal protective capacity of Fermented Black Ginseng (FBG) and its mechanism to reduce the cisplatin-induced nephrotoxicity. Nephrotoxicity was induced by a single intraperitoneal injection of cisplatin (20 mg/kg) and treated with white ginseng (WB) and FBG (200 mg/kg/day, orally) for 4 days before cisplatin treatment. Biochemical results showed that WG and FBG pretreatment significantly reduced the increase of blood urea nitrogen (BUN) and creatinine, and histopathological changes were meaningfully ameliorated. Cisplatin increased the production of reactive oxygen species (ROS) and depletion of Glutathione (GSH) in serum and kidney, whereas, WG or FBG administration markedly down-regulated. Moreover, the expression of nuclear factor-kappaB (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 was markedly suppressed by both WB and FBG. However, FBG pretreatment was more effective than those of WG in COX-2, iNOS, and IL-6 levels. Moreover, FBG treated mice significantly up-regulated the antioxidative enzymes. In HPLC analysis, the increasing ginsenoside contents that include Rg1, Re, Rb1, Rc, Rb3, Rd, Rg3, Rk1, and Rg5 by heat-processing were greater about 5.7 fold when fermentation additionally. Taken together, FBG may be a worthful candidate for the prevention of nephrotoxicity in patients receiving cisplatin.