Renal Enzyme Activity Research Articles

Antioxidant, anti-inflammatory and renoprotective effects of acidic-hydrolytic polysaccharides by spent mushroom compost (Lentinula edodes) on LPS-induced kidney injury

Increasing evidences have demonstrated that the reactive oxygen species play important roles in the initiation and progress of LPS-induced kidney injury (KI). The present work investigated the antioxidant, anti-inflammatory and renoprotective effects of acidic spent mushroom compost polysaccharides (ASMCP) by Lentinula edodes against the LPS-induced KI in mice. The results demonstrated that ASMCP showed anti-inflammatory effects on reducing the serum levels of TNF-α, IL-6 and IL-1β, inhibiting the elevation of lipid peroxidation, lowering the serum levels of BUN, CRE and UA, and improving the antioxidant status by enhancing renal enzyme activities (SOD, GSH-Px, CAT and T-AOC). Furthermore, the histological observations of renal cortex and renal medulla also indicated the potential renoprotective effects of ASMCP. These conclusions suggested that ASMCP might be suitable for functional foods and a potentially effective candidate medicine for the treatment of KI.

Nephroprotective Effect of Moringa Oleifera Seed Oil on Gentamicin-Induced Nephrotoxicity in Rats: Biochemical Evaluation of Antioxidant, Anti-inflammatory, and Antiapoptotic Pathways

Objective: Gentamicin is an efficacious aminoglycoside antibiotic widely used to treat life-threatening Gram-negative bacteria infections. However, its specific non-targeted induction of nephrotoxicity is a worrying clinical challenge. The study explored the nephroprotective effect of Moringa oleifera seed oil (MOO) against gentamicin-induced oxidative nephrotoxicity, pro-inflammation, and apoptosis in male Wistar rats. Method: Twenty-four rats divided into 4 groups (n = 6) were administered MOO (5 ml/kg) for 16 days and/or gentamicin (100 mg/kg bw/d, ip) injected from day 11 to day 16. The renal antioxidant enzyme activities reduced glutathione, lipid peroxidation, and serum renal markers. Urea and creatinine levels were estimated. The renal expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) were determined. Renal levels of inducible nitric oxide synthase (iNOS), nuclear factor-ĸB (NF-ĸB), and caspase-3 were determined to detect possible mechanism of inflammation and apoptosis with histology. Results: MOO prominently reduced serum creatinine and urea levels with amelioration of histopathological abrasions induced by gentamicin (GM). It significantly depressed oxidative stress through lowering of renal malondialdehyde (MDA) and elevation of renal superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, and reduced glutathione (GSH) level. MOO restored renal content of IL-1β, IL-6, TNF-α, and NO, coupled with the mechanistic downregulation of NF-ĸB, iNOS, and caspase-3 activities. The histopathological alterations were ameliorated by MOO. Conclusions: MOO possesses marked nephroprotective effect against GM-induced renal damage via modulating oxidative stress, inflammation, and apoptosis in Wistar rats.

Has vitamin E any shreds of evidence in cisplatin-induced toxicity.

Cisplatin is one of the highly consumed and effective antitumor agents whose clinical application is accompanied by nephrotoxicity adverse reaction. Also, other complications such as ototoxicity and hepatotoxicity are a matter of concern. Today, it is suggested that cisplatin-associated toxicities are mainly induced by free radicals production, which will result in oxidative organ injury. The evidence is growing over the protective effects of antioxidants on cisplatin-induced adverse reactions especially nephrotoxicity. The possible protective effects of vitamin E and its derivative in cisplatin-induced nephrotoxicity and ototoxicity are reviewed here at the light of pertinent results from basic and clinical research. Administration of vitamin E alone or in combination with other antioxidant agents could cause amelioration in oxidative stress biomarkers such as decreasing the level of malondialdehyde, reducing serum urea and creatinine, and also enhancing the activities of renal antioxidant enzymes including renal catalase, glutathione-S-transferase, and superoxide dismutase. Although the data from most of the studies are in favors of protective effects of vitamin E against cisplatin-induced toxicity, more clinical trials are needed to clarify the clinical importance of vitamin E administration as an antioxidant during cisplatin therapy in cancer condition.

Dose-Dependent Chemopreventive Effect of Methanol Extract of Carica papaya Seed on Potassium Bromate- Induced Nephrotoxicity in Rats

Aim: To investigate the effect of Carica papaya seed extract on KBrO3 - induced nephrotoxicity in rats. Renal toxicity was induced by a single oral dose of 100 mg/kg body weight of KBrO3.
 Study Design: Thirty (30) male albino rats were divided into six groups, five rats per group; normal control, KBrO3 control, papaya control and KBrO3 group administered with methanol seed extract of 200 mg/kg, 400 mg/kg and 600 mg/kg body weight for 48 hours.
 Place and Duration of Study: Department of Biochemistry Laboratory, Faculty of Basic Medical Sciences, Bayero University Kano, Nigeria, from April 2018 to August 2018.
 Methodology: Serum urea, creatinine, uric acid and electrolytes were determined using kits from randox laboratories. Furthermore, activities of renal brush border membrane marker enzymes namely γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), maltase (Mal) and leucine aminopeptidase (LAP) and some parameters of oxidative stress including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH) and malondialdehyde (MDA) were determined in homogenates prepared from renal cortex and medulla of the kidney of rats using colorimetric methods.
 Results: Administration of KBrO3 significantly (P<0.05) increases the serum levels of urea, creatinine, uric acid and all electrolytes studied in a dose-dependent fashion from 200mg/kg to 400mg/kg and 600mg/kg in that order. Furthermore, the activities of GGT, ALP, Mal and LAP decrease in renal homogenates with KBrO3 administration. Also the activities of CAT, SOD, GPx and level of GSH decreases while the level of MDA significantly (P<0.05) increases however concurrent administration of Carica papaya seed extract prevented all the KBrO3- induced changes in the biochemical parameters studied .
 Conclusion: It was suggested that methanol seed extract of Carica papaya possess nephroprotective effect against KBrO3 –induced renal toxicity and oxidative stress, and the most effective dose was 600 mg/kg body weight.

A new common functional coding variant at the DDC gene change renal enzyme activity and modify renal dopamine function

The intra-renal dopamine (DA) system is highly expressed in the proximal tubule and contributes to Na+ and blood pressure homeostasis, as well as to the development of nephropathy. In the kidney, the enzyme DOPA Decarboxylase (DDC) originating from the circulation. We used a twin/family study design, followed by polymorphism association analysis at DDC locus to elucidate heritable influences on renal DA production. Dense single nucleotide polymorphism (SNP) genotyping across the DDC locus on chromosome 7p12 was analyzed by re-sequencing guided by trait-associated genetic markers to discover the responsible genetic variation. We also characterized kinetics of the expressed DDC mutant enzyme. Systematic polymorphism screening across the 15-Exon DDC locus revealed a single coding variant in Exon-14 that was associated with DA excretion and multiple other renal traits indicating pleiotropy. When expressed and characterized in eukaryotic cells, the 462Gln variant displayed lower Vmax (maximal rate of product formation by an enzyme) (21.3 versus 44.9 nmol/min/mg) and lower Km (substrate concentration at which half-maximal product formation is achieved by an enzyme.)(36.2 versus 46.8 μM) than the wild-type (Arg462) allele. The highly heritable DA excretion trait is substantially influenced by a previously uncharacterized common coding variant (Arg462Gln) at the DDC gene that affects multiple renal tubular and glomerular traits, and predicts accelerated functional decline in chronic kidney disease.

Renal chymase-dependent pathway for angiotensin II formation mediated acute kidney injury in a mouse model of aristolochic acid I-induced acute nephropathy.

Angiotensin-converting enzyme (ACE) is the primary enzyme that converts angiotensin I (Ang I) to angiotensin II (Ang II) in the renin-angiotensin system (RAS). However, chymase hydrates Ang I to Ang II independently of ACE in some kidney diseases, and it may play an important role. The present study investigated whether chymase played a crucial role in aristolochic acid I (AAI)-induced nephropathy. C57BL/6 mice were treated with AAI via intraperitoneal injection for an accumulated AAI dosage of 45 mg/kg body weight (BW) (15 mg/kg BW per day for 3 days). The animals were sacrificed after acute kidney injury development, and blood, urine and kidneys were harvested for biochemical and molecular assays. Mice exhibited increased serum creatinine, BUN and urinary protein after the AAI challenge. Significant infiltrating inflammatory cells and tubular atrophy were observed in the kidneys, and high immunocytokine levels were detected. Renal RAS-related enzyme activities were measured, and a significantly increased chymase activity and slightly decreased ACE activity were observed in the AAI-treated mice. The renal Ang II level reflected the altered profile of RAS enzymes and was significantly increased in AAI-treated mice. Treatment of AAI-induced nephropathic mice with an ACE inhibitor (ACEI) or chymase inhibitor (CI; chymostatin) reduced renal Ang II levels. The combination of ACEI and CI (ACEI+CI) treatment significantly reversed the AAI-induced changes of Ang II levels and kidney inflammation and injuries. AAI treatment significantly increased renal p-MEK without increasing p-STAT3 and p-Smad3 levels, and p-MEK/p-ERK1/2 signalling pathway was significantly activated. CI and ACEI+CI treatments reduced this AAI-activated signaling pathway. AAI-induced nephropathy progression was significantly mitigated with CI and ACEI+CI treatment. This study elucidates the role of RAS in the pathogenesis of AAI-induced nephropathy.

Taurine Ameliorates Thyroid Hypofunction and Renal Injury in L-NAME-Induced Hypertensive Rats.

There is a growing global interest in hypertension due to its associated complications including renal dysfunction in patients. The thyroid system reportedly regulates renal function in both animal and human. The present study investigated the therapeutic efficacy of taurine on renal and thyroid dysfunctions in hypertensive rats. Hypertension was induced by oral administration of nitric oxide synthase inhibitor, N-nitro L-arginine-methyl-ester (L-NAME), at 40 mg/kg body weight to the male Wistar rats for 14 consecutive days. The hypertensive rats were subsequently treated with either taurine (100 and 200 mg/kg) or reference drug atenolol (10 mg/kg) for another 14 consecutive days. Hypertensive rats showed renal damage evidenced by elevated plasma creatinine and urea levels when compared with normotensive control rats. Furthermore, L-NAME-induced hypertensive rats showed decreased circulatory concentrations of thyroid stimulating hormone, thyroxine, triiodothyronine and the ratio of triiodothyronine to thyroxine. The marked decrease in the renal antioxidant enzyme activities and nitric oxide level was accompanied by significant increase in myeloperoxidase activity and biomarkers of oxidative stress in hypertensive rats. Histological examination of kidneys from hypertensive rats revealed congestion of blood vessels, hemorrhagic lesion and disorganized glomerular structure. However, treatment with taurine or atenolol significantly reversed the suppression of thyroid function, ameliorated renal oxidative stress and histopathological lesions in L-NAME-induced hypertensive rats. Taurine may be a useful chemotherapeutic supplement in enhancing renal and thyroid functions in hypertensive patients.

Dysequilibrium of the PTH-FGF23-vitamin D axis in relapsing remitting multiple sclerosis; a longitudinal study

BackgroundParathyroid glands of people with relapsing remitting multiple sclerosis (RRMS) fail to respond to low serum 25-hydroxyvitamin D (25OHD) and low serum calcium, which are stimuli for parathyroid hormone (PTH) secretion. This led us to hypothesise: that there is suppression of PTH in RRMS due to higher than normal serum concentrations of fibroblast growth factor 23 (FGF23). We therefore sought evidence for dysregulation of the PTH-FGF23-vitamin D axis in RRMS.MethodsLongitudinal study (winter to summer) with fasting venepunctures. For RRMS subjects who recruited a healthy control (HC) friend, pairs analyses were performed. For each pair, the within-pair difference of the variable of interest was calculated (RRMS minus HC). Then, the median of the differences from all pairs was compared against a median of zero (Wilcoxon) and the 95% confidence interval of that median difference (CI) was calculated (Sign Test).ResultsRRMS had lower winter PTH than HC, P = 0.005, (CI -2.4 to 0.5 pmol/L, n = 28 pairs), and lower summer PTH, P = 0.04, (CI -1.8 to 0.5, n = 21 pairs). Lower PTH associates physiologically with lower intact FGF23 (iFGF23), yet RRMS had higher iFGF23 than HC in winter, P = 0.04, (CI -3 to 15 pg/mL, n = 28 pairs) and iFGF23 levels comparable to HC in summer, P = 0.14, (CI -5 to 13, n = 21 pairs). As PTH stimulates and FGF23 reduces, renal 1-alpha hydroxylase enzyme activity, which synthesises serum 1,25-dihyroxyvitamin D (1,25(OH)2D) from serum 25OHD, we examined the ratio of serum 1,25(OH)2D to serum 25OHD. In winter, this ratio was lower in RRMS versus HC, P = 0.013, (CI -1.2 to - 0.3, n = 28 pairs).ConclusionsThis study revealed a dysequilibrium of the PTH-FGF23-vitamin D axis in RRMS, with lower plasma PTH, higher plasma iFGF23 and a lower serum 1,25(OH)2D to 25OHD ratio in RRMS compared with HC subjects. This dysequilibrium is consistent with the study hypothesis that in RRMS there is suppression of the parathyroid glands by inappropriately high plasma concentrations of iFGF23. Studying the basis of this dysequilibrium may provide insight into the pathogenesis of RRMS.

Effects of δ-tocotrienol on ochratoxin A-induced nephrotoxicity in rats.

Ochratoxin A (OTA), is a natural contaminant of the food chain worldwide involved in the development of different type of cancers in animals and humans. Several studies suggested that oxidative damage might contribute to increase the cytotoxicity and carcinogenicity capabilities of OTA. The aim of this study was to evaluate the possible protective effect of δ-tocotrienol (Delta), a natural form of vitamin E, against OTA-induced nephrotoxicity. Male Sprague-Dawley rats were treated with OTA and/or Delta by gavage for 14 days. Our results shown that OTA treatment induced the increase of reactive oxigen species production correlated to a strong reduction of Glomerular Filtration Rate (GFR) and absoluted fluid reabsorption (Jv) with conseguent significant increase in blood pressure. Consistent, we noted in the kidney of rats treated with OTA, an increase in malondialdheyde and dihydroethidium production and a reduction of the activity of the catalase, superoxide dismutase, and glutathione peroxidase. Conversly, in the rat group subjected to the concomitant treatment OTA plus Delta, we observed the restored effect, compared the OTA treatment group, on blood pressure, GFR, Jv, and all activities of renal antioxidant enzymes. Finally, as far as concern the tissue damage induced by OTA and measured evaluating fibronectin protein levels, we observed that in OTA plus Delta group this effect is not restored. Our findings releval that a mechanism underlying the renal toxicity induced by OTA is the oxidative stress and provide a new rationale to use a Delta in order to protect, at least in part, against OTA-induced nephrotoxicity.

Concomitant administration of resveratrol and insulin protects against diabetes mellitus type-1-induced renal damage and impaired function via an antioxidant-mediated mechanism and up-regulation of Na+/K+-ATPase

This study investigated if a combination of resveratrol (RES) and insulin could reverse type 1 diabetic mellitus-induced (T1DM) nephropathy and illustrates mechanism of action. Rats were divided into six groups (n = 10/group) as follows: control, control + RES (20 mg/kg), T1DM, T1DM + RES, T1DM + insulin (1 U/g), and T1DM + RES + insulin and treated for eight weeks. While individual administrations of both drugs significantly but partially restored renal function and cortex architectures, combination therapy of both RES and insulin produced the maximum improvements. Mechanism of actions revealed a synergist effect of both drugs due to hypoglycaemic effect of insulin and the ability of both drugs to increase renal cortex antioxidant enzymes activities, inhibit lipid peroxidation, and up-regulate Na+/K+-ATPase, independent of each others. In conclusion, these data suggest the combined therapy with insulin and RES could provide an excellent combined drug therapy against T1DM-induced nephropathy.

Effect of Vegetarian Diet and Functional Meat Based Diet on Serum Lipid Profiles, Liver Functions and Oxidative Stress Related Indices: A Mice Model Study

Epidemiological evidence suggests that intake of high amount of non-vegetarian diet is associated with increased risk of chronic diseases including atherosclerosis, hyperlipidemia and cancers. But, the research study on the effect of functional meat product in physiological functions of health is still pending. Therefore, the aim of this study was to elucidate effect of whole grain cereal flours and some plant derived bioactive compounds intake on antioxidant activity, MDA content, serum lipid profile, hepatic and renal functions and tissue histopathology of vital organs were examined in mice model study. For this, a total thirty six adult male Swiss albino mice were randomly divided into three groups (3×12): one group fed control diet (vegetarian diet, CD), another group fed control wafers (CW) and the third group fed functional wafers (FW). The FW contained whole grain oat and sorghum flours, apple peel paste, oregano, aloe vera gel and vitamin E. Result indicated that FW lowered overall serum total cholesterol (TC) and LDL-C levels but HDL-C remain unchanged. Compared with control group, the TC and LDL-C in FW group were lowered by 15.61 and 16.51 mg/dL, respectively. The TGL was lowest in mice received CD. The serum glucose level was decreased in CW and FW fed mice. The activity of hepatic and renal enzymes were lowered (P<0.01) with the feeding of FW. The antioxidant enzymes viz., CAT and GSH-Px, however increased in the FW group by 14.0 and 2.27 U/mL respectively (P<0.05). The antioxidant enzymes in FW group mice decreased the MDA formation. This it was concluded that FW intake could greatly help in amelioration of oxidative stress related chronic diseases besides improving most of the lipid profile parameters.

The Possible Protective Effect of Alpha-Lipoic Acid against Acute Ricin-Induced Nephrotoxicity in Adult Male Albino Rats

Background: Ricin toxin is considered one of the most potent plant-derived toxins. It induces rapid and irreversible toxic effects through many mechanisms with special concern to inhibition of protein synthesis and oxidative stress resulting in cell death. Moreover, ricin could be used as a terrorist weapon which indicates the importance of finding a specific treatment. Alpha lipoic acid (ALA) possesses almost all characters of an ideal antioxidant; thereby it is suggested to be used against ricin toxicity. Aim of the work: The current study aimed at investigating the acute toxic effects of ricin on the kidneys of adult male albino rats and to appraise the possible protective effect of ALA in altering ricin-induced nephrotoxicity. Material & Methods: the present study was carried out on 60 adult male albino rats; they were divided into four groups. Group I: ten rats were intraperitoneally injected by 0.9% saline. Group II:tenrats were intraperitoneally injected by 100 mg/kg ALA. Group III: twentyrats were subcutaneously injected once with 25 µg/kg body weight of ricin solution. Group IV: twenty rats were injected by 100 mg/kg ALA, 15 minutes prior to single injection of 25 μg/kg body weight of ricin solution, and then reinjected with the same dose of ALA immediately after ricin injection. Survival time, renal function tests, renal malondialdehyde (MDA), renal superoxide dismutase (SOD) and catalase enzyme activities were recorded. Kidney samples were used for electron microscopic examination. Results: Ricin induced nephrotoxicity with significant increase of renal function tests, renal MDA and catalase activity with significant decrease of SOD. Also, the kidney samples of ricin-treated animals revealed focal ultrastructural changes in renal corpuscles, proximal and distal convoluted tubules. On the other hand, most of ricin-induced injuries were much improved after administration of ALA together with ricin. Conclusion: Ricin produces oxidative nephrotoxic effects that markedly improved by the effective antioxidant properties of alpha lipoic acid.

Comparative study of radioprotective effects of selenium nanoparticles and sodium selenite in irradiation-induced nephropathy of mice model

Purpose: The current study was undertaken to evaluate radioprotective effects of selenium (Se) nanoparticles in irradiation-induced nephropathy of mice model compared to sodium selenite.Materials and methods: Forty-five mice were divided into three major groups including control, Se nanoparticle, and sodium selenite. Each major group was further subdivided into three more groups receiving various doses of 0, 2, and 8 Gy gamma irradiation. Both of the supplements were administered intraperitoneally with the dose of 0.1 mg/kg for 14 consecutive days. At the end of each week, the animals were exposed to gamma radiation and 48 h after the last exposure, the animals were humanely euthanized, then blood and renal tissue samples were taken. Serum creatinine, urea, cystatin C, and beta-2-microglobulin levels as well as activities of renal antioxidant enzymes, superoxide dismutase, glutathione peroxidase and catalase, also malondialdehyde level, total antioxidant capacity, renal tissue Se content, and histopathological features were assessed.Results: The results showed that both of the supplements could normalize aforementioned indices. However, selenium nanoparticles (Se-NPs) were more effective than sodium selenite.Conclusions: Conclusively, Se-NPs as an emerging potent antioxidant agent can protect against irradiation-induced nephropathy.

Antioxidant and Nephroprotective Potential of Aegle marmelos Leaves Extract

ABSTRACTThe nephroprotective activity of hydro-alcoholic (HAEAM) and ethyl acetate (EAEAM) extracts of Aegle marmelos leaves were evaluated against nephrotoxicity induced by cisplatin (CP), a widely used chemotherapeutic agent in cancer therapy. Wistar rats were treated with CP (6 mg.kg–1; i.p.). Treatment groups received the same dose of CP, along with HAEAM and EAEAM (200 and 400 mg.kg–1) orally for 5 d. Blood urea nitrogen (BUN), serum creatinine, and antioxidant enzymes were estimated in renal tissues. EAEAM exhibited minimum IC50 values 6.13 ± 1.05, 67.34 ± 1.7, 59.7 ± 3.9, and 49.17 ± 2.19 μg.mL–1. EAEAM (400 mg.kg–1) decreased the creatinine levels from 2.29 ± 0.387 to 0.96 ± 0.095 mg.dL–1 and BUN from 92.06 ± 7.949 to 38.18 ± 5.686 mg.dL–1 and restored the activities of renal antioxidant enzymes, decreased the lipid peroxidasde (LPO) levels from 158.70 ± 3.542 to 106.91 ± 5.876 nM.g–1, and increased superoxide dismutase (SOD) levels from 12.59 ± 0.463 to 29.95 ± 5.222 U.g–1, glutathione (GSH) from 0.24 ± 0.029 to 0.57 ± 0.048 μM.g–1, and catalase (CAT) from 1.14 ± 0.067 to 3.27 ± 0.296 U.mg–1).

Potential protective effects of vitamin E in cisplatin-induced toxicity

Introduction: Cisplatin is one of highly consumed and effective antitumor agents while its clinical application is accompanied by nephrotoxicity adverse reactions. Also other complication such as ototoxicity and hepatotoxicity are matter of concern. Today, it is suggested that cisplatin-induced toxicities are mainly induced by free radical production, leading to oxidative organ injury. Evidences are growing over the protective effects of antioxidants on cisplatin induced adverse reactions especially nephrotoxicity. The possible protective effects of vitamin E and its derivative in cisplatin-induced nephrotoxicity and ototoxicity will be reviewed here at the light of pertinent results from basic and clinical researches. Methods: All available in vitro and in vivo studies, clinical trials, and meeting abstracts in English language that examined the protective effects of vitamin E and its derivative in cisplatin-induced toxicity were considered. Materials were obtained by searching ELSEVIER, web of knowledge, PubMed, Scopus, clinical trials, and Cochrane database of systematic reviews. Results: Administration of vitamin E alone or in combination with other antioxidant agents could cause amelioration in oxidative stress biomarkers such as decrease in level of malondialdehyde, reduction in serum urea and creatinine and also enhancing the activities of renal antioxidant enzymes including renal catalase, glutathione-S-transferase and superoxide dismutase. Conclusion: Although the data from most of studies were in favors of protective effects of vitamin E against cisplatin-induced toxicity, more clinical trials are needed to clarify the clinical importance of vitamin E administration as an antioxidant during cisplatin therapy in cancer condition.

Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling

Cisplatin is a chemotherapeutic agent widely used in the treatment of various cancers. However, cisplatin can induce nephrotoxicity and neurotoxicity, limiting its dosage and usage. Galangin, a natural flavonol, has been found to exhibit anti-oxidant and anti-inflammatory effects in vivo. Here, we investigated the effects of galangin on cisplatin-induced acute kidney injury (AKI) and its molecular mechanisms in mice. Galangin administration reduced the cisplatin-induced oxidative stress by decreasing renal MDA and 3-NT formations. Galangin administration also increased renal anti-oxidative enzyme activities (SOD, GPx, and CAT) and GSH levels depleted by cisplatin. Furthermore, galangin administration inactivated stress-induced Nrf2 protein and its downstream products, HO-1 and GCLC. In terms of the inflammatory response, galangin administration reduced IκBα phosphorylation, NF-κB phosphorylation and nuclear translocation, and then inhibited cisplatin-induced secretions of pro-inflammatory TNF-α, IL-1β and IL-6. In addition, cisplatin-induced ERK and p38 phosphorylations were inhibited by galangin administration. In terms of cell death, galangin administration reduced levels of p53, pro-apoptotic Bax and activated caspase-3 to inhibit the cisplatin-induced apoptosis. Galangin administration also reduced the expression levels of RIP1 and RIP3 to inhibit cisplatin-induced RIP1/RIP3-dependent necroptosis. Therefore, galangin administration significantly ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation, and cell death through inhibitions of ERK and NF-κB signaling pathways. Galangin might be a potential adjuvant for clinical cisplatin therapy.

Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway

ABSTRACTObjectives: Arsenic is a ubiquitous element that is widely distributed in the environment to which man and animals are exposed. Cardiovascular disease is one of the aftermaths of chronic arsenic exposure-related morbidity and mortality. This study sought to investigate the possibility of reversal from arsenic-induced cardio-renal toxicity following exposure and subsequent withdrawal. The study also seeks to understand the mechanism of action of this reversal.Methods: Rats were orally exposed to sodium arsenite at 10, 20 and 40 mg/kg daily for 4 weeks followed by 4 weeks of withdrawal.Results: Exposure to arsenic caused a significant increase in malondialdehyde, H2O2 generation but decrease total thiol and reduced glutathione levels in both cardiac and renal tissues. Furthermore, increases in superoxide dismutase, glutathione-S-transferase and catalase with significant increases in glutathione peroxidase activities were observed in the cardiac tissues. On the contrary, a significant reduction in the renal antioxidant enzyme activity was recorded following exposure. Also, antioxidant defense system did not return to apparent values after arsenic withdrawal. Immunohistochemistry revealed a reduction in the expression of the pro-survival protein–protein kinase B (Akt/PKB) following exposure to arsenic and this was not reversed by withdrawalDiscussion: Exposure to arsenic caused cardio-renal toxicity via induction of oxidative stress and down-regulation of Akt/PKB expressions.

Amelioration of Gamma-hexachlorocyclohexane (Lindane) induced renal toxicity by Camellia sinensis in Wistar rats.

Aim:A study to assess the toxic effects of gamma-hexachlorocyclohexane (γ-HCH) (lindane) and ameliorative effects of Camellia sinensis on renal system has been carried out in male Wistar rats.Materials and Methods:Four groups of rats with 18 each were maintained under standard laboratory hygienic conditions and provided feed and water ad libitum. γ-HCH was gavaged at 20 mg/kg b.wt. using olive oil as vehicle to Groups II. C. sinensis at 100 mg/kg b.wt. was administered orally in distilled water to Group IV in addition to γ-HCH 20 mg/kg b.wt. up to 45 days to study ameliorative effects. Groups I and III were treated with distilled water and C. sinensis (100 mg/kg b.wt.), respectively. Six rats from each group were sacrificed at fortnight intervals. Serum was collected for creatinine estimation. The kidney tissues were collected in chilled phosphate buffer saline for antioxidant profile and in also 10% buffered formalin for histopathological studies.Results:γ-HCH treatment significantly increased serum creatinine and significantly reduced the renal antioxidative enzymes catalase, superoxide dismutase, and glutathione peroxidase. Grossly, severe congestion was noticed in the kidneys. Microscopically, kidney revealed glomerular congestion, atrophy, intertubular hemorrhages, degenerative changes in tubular epithelium with vacuolated cytoplasm, desquamation of epithelium and urinary cast formation. A significant reduction in serum creatinine levels, significant improvement in renal antioxidant enzyme activities and near to normal histological appearance of kidneys in Group IV indicated that the green tea ameliorated the effects of γ-HCH, on renal toxicity.Conclusion:This study suggested that C. sinensis extract combined with γ-HCH could enhance antioxidant/detoxification system which consequently reduced the oxidative stress thus potentially reducing γ-HCH toxicity and tissue damage.

Vasopressin lowers renal epoxyeicosatrienoic acid levels by activating soluble epoxide hydrolase.

Activation of the thick ascending limb (TAL) Na+-K+-2Cl- cotransporter (NKCC2) by the antidiuretic hormone arginine vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined. Here, we show that chronic treatment of AVP-deficient Brattleboro rats with the AVP V2 receptor analog desmopressin (dDAVP; 5 ng/h, 3 days) significantly lowered renal EET levels (-56 ± 3% for 5,6-EET, -50 ± 3.4% for 11,12-EET, and -60 ± 3.7% for 14,15-EET). The abundance of the principal EET-degrading enzyme soluble epoxide hydrolase (sEH) was increased at the mRNA (+160 ± 37%) and protein levels (+120 ± 26%). Immunohistochemistry revealed dDAVP-mediated induction of sEH in connecting tubules and cortical and medullary collecting ducts, suggesting a role of these segments in the regulation of local interstitial EET signals. Incubation of murine kidney cell suspensions with 1 μM 14,15-EET for 30 min reduced phosphorylation of NKCC2 at the AVP-sensitive threonine residues T96 and T101 (-66 ± 5%; P < 0.05), while 14,15-DHET had no effect. Concomitantly, isolated perfused cortical thick ascending limb pretreated with 14,15-EET showed a 30% lower transport current under high and a 70% lower transport current under low symmetric chloride concentrations. In summary, we have shown that activation of AVP signaling stimulates renal sEH biosynthesis and enzyme activity. The resulting reduction of EET tissue levels may be instrumental for increased NKCC2 transport activity during AVP-induced antidiuresis.

NEPHROPROTECTIVE EFFECT OF AQUEOUS EXTRACT OF SOLANUM NIGRUM LINN LEAVES OR SEEDS AND THEIR MIXTURE AGAINST GENTAMICIN-INDUCED NEPHROTOXICITY IN RATS

Abstract The present study aimed to elucidate the nephroprotective effect of different doses of aqueous extract of Solanum Nigrum Linn (AE-SN)leaves or seeds and their mixture against gentamicin-induced nephrotoxicity in rats. Forty eight mature male rats weighted (160±5g) were randomly divided into eight groups 6 rats each. Group (1) rats were fed on basal diet and served as a negative control, while the other 7 groups were intoxicated by a single intraperioneal dose (100 mg/kg) of gentamicin to rats at the 4th week; once daily for end of the experiment (4 weeks) for induction of nephrotoxicity. Group (2) was kept intoxicated ( a positive control group ) while groups 3, 4, 5 and 6 were pre- treated orally with AE-SN extract of leaves and seeds in a dose of 250 and 500mg/kg b.wt., respectively for 4 weeks. Groups 7 and 8 were pre- treated orally with a mixture of aqueous extract of Solanum Nigrum Linn leaves and seeds in a dose of 250 and 500mg/kg b.wt respectively for 4 weeks.Feed intake was calculated daily and body weight gain was recorded weekly. Blood samples were collected and kidneys were weighted, dissected out and taken for biochemical analyses and histopathological study. Pre- treatment with AE-SN extract of leaves or seed and their mixture improved feed intake and increased body weight gain and normalized kidney weight compared to GM intoxicated rats. Also AE-SN significantly improved levels of renalmarkers and maintaining the electrolyte balance by decreasing serum level of some mineral element (Na, K and P), and increase level of calcium and vit. D. in serum compared to negative control group. Improved renal function by AE-SN treatment caused an increase in Renin , Erythropoietin (EPO) and parathyroid hormones. There were also an increase in renal antioxidant enzyme activity and partial amelioration of renal degeneration. In conclusion AE-SN aqueous extract of leave was more effective than aqueous extract of seeds. Pre-treatment with AE-SN mixture at high doses, significantly normalized level of renal markers and antioxidant activities. Ameliorative effects of AE-SN leaves or seeds and their mixture against gentamicin induced nephrotoxicity may be attributed to their antioxidant properties. Key words: nephrotoxicity, SolanumNigrumLinn gentamicin & rat.