Renal Damage In Rats Research Articles

The Antioxidant, Anti-Apoptotic, and Proliferative Potency of Argan Oil against Betamethasone-Induced Oxidative Renal Damage in Rats.

Simple SummaryThe present study aimed to investigate the protective effect of argan oil against nephrotoxic effect following overdose and long-term administration of betamethasone. The results revealed that betamethasone induced hematological changes, including reduction of red blood cells with leukocytosis, neutrophilia, monocytosis, lymphocytopenia, and marked thrombocytopenia. Moreover, betamethasone caused significant increase of serum urea and creatinine levels; renal malondialdehyde and nitric oxide contents associated with significant decrease of reduced glutathione content. Betamethasone also caused vascular, degenerative, and inflammatory histopathological alterations in kidney tissue along with increase of Bax and caspase-3 expressions and decrease of B-cell lymphoma-2 (Bcl-2) and proliferating cell nuclear antigen (PCNA) expressions. Conversely, the concomitant administration of argan oil (0.5, 1 mL/kg) with betamethasone ameliorated the aforementioned hematological, biochemical, pathological, and histochemical adverse effects. In conclusion, overdose and long-term administration of betamethasone could induce hematological changes and severe renal damage mediated by oxidative, apoptotic and proliferative mechanisms via increasing renal functions biomarkers and altering oxidant/antioxidant status along with pathological lesions and imbalance of Bax/Bcl-2 ratio that positively correlates with up-regulation of caspase-3 and down-regulation of PCNA in kidney tissue. However, argan oil could potentially protect against betamethasone- induced renal damage, in a dose-dependent manner, via its antioxidant, anti-apoptotic and proliferative properties.The present study aimed to investigate the protective effect of argan oil (AO) against nephrotoxic effects following overdose and long-term administration of betamethasone (BM). The phytochemical compositions of AO were assessed using GC/MS. Forty eight male Wister albino rats were divided into six groups and treated for 3 successive weeks. The control group was orally administrated distilled water daily, the BM group received BM (1 mg/kg, IM, day after day), AO/0.5 and AO/1 groups received AO (0.5 mL/kg, 1 mL/kg, orally, daily, respectively), BM + AO/0.5 group and BM + AO/1 group. The results revealed that BM induced hematological changes, including reduction of red blood cells with leukocytosis, neutrophilia, monocytosis, lymphocytopenia, and thrombocytopenia. Moreover, BM caused a significant increase of serum urea and creatinine levels, and renal malondialdehyde and nitric oxide contents with significant decrease of reduced glutathione content. BM also caused vascular, degenerative, and inflammatory histopathological alterations in kidney, along with an increase in the Bax/Bcl-2 ratio, activation of caspase-3, and decrease of proliferating cell nuclear antigen expression. Conversely, the concomitant administration of AO (0.5, 1 mL/kg) with BM ameliorated the aforementioned hematological, biochemical, pathological, and histochemical BM adverse effects. In conclusion, AO has protective effects against BM-induced renal damage, possibly via its antioxidant, anti-apoptotic, and proliferative properties.

CP-25 improves nephropathy in collagen-induced arthritis rats by inhibiting the renal inflammatory response

Paeoniflorin-6′-O-benzene sulfonate (CP-25) is a derivative of paeoniflorin. We previously confirmed that CP-25 inhibits inflammatory responses in several arthritis animal models. The aim of the present study was to investigate the beneficial effects of CP-25 on renal damage in rats with collagen-induced arthritis (CIA). CIA was induced in rats, which were orally administered CP-25 (25, 50 and 100 mg/kg/day) for 24 days. The levels of plasma blood urea nitrogen (BUN) and urine protein in CIA rats were measured. Pathological changes in renal tissues and joints were observed, and inflammatory cell infiltration was evaluated by immunohistochemistry. Moreover, renal inflammatory mediators and transporters were measured by western blotting. We found that CP-25 not only inhibited arthritis manifestations but also improved renal pathological manifestations and kidney injury by decreasing serum BUN and urine protein levels. Further study revealed that CP-25 treatment reduced the number of renal CD68+ cells and downregulated the levels of MCP-1, TNF-α and IL-6 in CIA rats. On the other hand, we noted that CP-25 decreased the ratios of phosphorylated NF-κB p65 (p-p65) to total p65 and p-IκBα to total IκBα in CIA rats, suggesting that CP-25 blocked NF-κB activation. Finally, we observed that CP-25 restored the abnormal expression of OAT1 and OCT1 in the renal tissues of CIA rat. Our data indicate that CP-25 ameliorates kidney damage in CIA rats, and this beneficial effect is closely related to inhibiting renal inflammation and the abnormal expression of transporters.

Effects of inflammatory response on renal function and TGF-β1 pathway of rats with aging-related kidney damage by upregulating the expression of CD36.

The aim of this study was to explore the effects of inflammatory response on renal function and TGF-β1 pathway of rats with aging-related kidney damage by upregulating the CD36 expression. A total of 70 pathogen free (PF) Sprague-Dawley (SD) male rats were enrolled. The rats injected with normal saline and D-galactose were assigned to a control group and a model group, respectively. Those injected with both D-galactose and different concentrations of casein were assigned to casein A, B, and C groups accordingly, and 16 rats injected with D-galactose and with CD36 gene knocked out were assigned to a treatment group. The following methods were employed to determine the following factors of the rats: ELISA for serum inflammatory factors, Western blot for CD36 in kidney tissues, Real Time-PCR for TGF-β1, and Smad (2, 3, and 7) mRNA, radioimmunoassay for hyaluronic acid (HA) and laminin (LN), and colorimetry for the expression quantity of plasma superoxide dismutase (SOD) and malondialdehyde (MDA). An automatic biochemical analyzer was used to determine blood, urine, and renal function indexes. After successful modeling, the model group showed significantly higher inflammatory indexes than the control group. The relative expression of CD36 in the model group was significantly higher than that in the control group and treatment group, and significantly lower than that in the casein groups. Both inflammatory indexes and relative expression of CD36 increased with the increase of casein concentration in the casein groups. Groups with severer inflammatory response showed higher renal function indexes, and higher expression of TGF-β1, Smad2, Smad3, HA, LN, and MDA, and those with decreased CD36 level showed lower renal function index levels. The Smad7 expression and SOD were contrary. Inflammatory stress can promote the CD36 expression in renal tissues of aging rats and oxidative stress and affect TGF-β1/Smad pathway, thus aggravating renal fibrosis and renal damage in rats.

INVESTIGATING EFFECTS OF 7,8-DISUBSTITUTED DERIVATIVE OF THEOPHYLLINE (BENOPHYLLINE) ON FREE-RADICAL OXIDATION IN RENAL INJURY OF RATS

This article highlights the pharmacological study of new 7,8-disubstituted derivative of theophylline, the substance conditionally named benophylline. Based on the literature data and previous studies of compounds of this class, it has been concluded that studying the effect of benophylline on the pro-antioxidant system under simulated pathologies is of great interest and importance.
 The study of antihypoxic action of 7,8-disubstituted theophylline in rats was carried out under modelled normobaric hypoxia with hypercapnia (in an enclosed space). It has been found out the application of 7-n-methylbenzyl-8-substituted polyphosphonates increases the longevity of rats in the conditions described above that evidences the improvement of metabolic processes in mitochondrial respiratory chain.
 Based on the results of screening studies, we selected 7,8-disubstituted derivative of theophylline (benophylline) as a leading substance for further investigation. The purpose of the study was to evaluate the efficacy of benophylline for the pharmacological correction of free radical processes in experimental renal damage in rats based on the evaluation of the expression of lipid peroxidation and antioxidant protection.
 Materials and methods: blood serum, homogenate and rat kidney tissues were the study materials. The study of the protective effect of benophylline on the functional state of the kidneys was investigated on experimental model of acute renal injury by introducing 50% water solution of glycerol (myoglobin nephropathy). Pathogenesis of this model was described in the methodological recommendations by C. Yu. Shtrygol, V. M. Lysovoi, I. A. Zupanetz et al. in «Methods of experimental modeling of kidney damage for pharmacological research». The content of TBK-R was determined spectrophotometrically by reaction with thiobarbituric acid.
 Glutathione recovered activity was determined spectrophotometrically in reaction with Elman's reagent using the method of Beutler E. D. et al. The catalase activity was assessed by the method of M.A. Koroluk et al. The influence of benophylline on the morphological state of the renal parenchyma was assessed on the modeled myoglobin nephropathy. The activity of gamma-glutamyltranspeptidase in serum was evaluated photometrically using a reagent test kit (“Filisit”). Statistical processing of the results was performed using the STATISTICA 8.0 software package, with the mean value, standard error of the mean confidence interval (p≤0.05). The microscopic study of microproducts was performed under the Granum microscope. Micrographs were taken with a Granum DMC 310 digital camera. The images were processed on a Pentium 2.4 GHz computer using Toup View software.
 Research results: Under the influence of benophylline, the processes of LPO and AOP became normalized, the expressiveness of degradation of the nephrocytes decreased, the microscopic picture of renal excretion in all rats got normalized. At the same time, 62.5% of the rats had the morphological condition of kidneys close to the intact control, and 37.5% of the animals were noticed to demonstrate a significant decrease in the dyscirculatory abnormalities, inflammatory manifestations and signs of nephrocyte regeneration.
 Conclusions: The ability of benophylline to inhibit the processes of free radical oxidation and to enhance antioxidant protection has been found out. The study has shown benophylline enhances regenerative effect kidney tissues.

Role of some natural anti-oxidants in the down regulation of Kim, VCAM1, Cystatin C protein expression in lead acetate-induced acute kidney injury.

Lead is a dangerous systemic toxicant and can provoke life-threatening renal injury. The plan of this study was to evaluate the potential impact of curcumin (CRMN) and L-ascorbic acid (L-ascb) alone or together to counteract lead acetate (Pb-acetate)-induced renal damage in rats and to find out the underlying mechanisms of action of these nutraceuticals. Pb-acetate (100mg/kg/day, i.p.) was injected in male rats along with L-ascb (250mg/kg/day) and/or CRMN (200mg/kg/day) orally for 7days. Pb-acetate administration increased serum urea, creatinine and uric acid. Renal tissue showed a marked depletion in reduced glutathione level and superoxide dismutase activity and elevation in nitric oxide and malondialdehyde levels. Serum C-reactive protein and IL-1β levels were elevated. Up-regulation of the expression of kidney injury molecule, vascular adhesion molecule-1 and Cystatin C were noticed after Pb-acetate administration. DNA fragmentation was also increased in renal tissues. Histopathological examination revealed a destructed partial layer of Bowman's capsule, proximal and distal convoluted tubules. Treatment with the aforementioned antioxidants ameliorated most of the altered measured biomarker levels. Interestingly, the combination of L-ascb and CRMN showed the superlative protective effect against Pb-acetate-induced nephrotoxicity.

Ameliorative Effect of Rhoifolin in Cisplatin-Induced Nephrotoxicity via Regulating Nuclear Factor-κB Pathway

Dose-dependent nephrotoxicity limits the therapeutic use of cisplatin in tumor chemotherapy. Natural compounds show a protective effect against cisplatin-induced nephrotoxicity. Rhoifolin is a flavone glycoside that demonstrates antioxidant and antiproliferative effects. The influence and mechanism of rhoifolin on cisplatin-induced nephrotoxicity were investigated in this study. First, a rat model of cisplatin-induced nephrotoxicity was established. Intraperitoneal administration of cisplatin induced renal damage in rats as demonstrated by a decrease in body weight, increase in blood urea, nitrogen and creatinine, and destruction of histological integrity. However, treatment with rhoifolin attenuated cisplatin-induced nephrotoxicity. Second, cisplatin induced oxidative stress and inflammatory response in rats as demonstrated by a decrease in superoxide dismutase, glutathione, glutathione S-transferase and catalase, and an increase in malondialdehyde, tumor necrosis factor-α, and interleukin-6. Also, the administration of rhoifolin led to alleviation of cisplatin-induced oxidative stress and inflammatory response. Finally, cisplatin activated the nuclear factor-kappa B signaling pathway via degradation and phosphorylation of IκBα (inhibitor of kappa B). Administration of rhoifolin inhibited nuclear translocation of NF-κB via down-regulation of phospho-IκBα and phospho-p65, as well as up-regulation of IκBα. In conclusion, the administration of rhoifolin attenuated cisplatin-induced renal damage, oxidative stress and inflammatory response through inhibition of the NF-κB signaling pathway, suggesting a potential adjunct candidate for cisplatin in tumor treatment.

Prospective Protective Effect of Ellagic Acid as a SIRT1 Activator in Iron Oxide Nanoparticle-Induced Renal Damage in Rats.

Despite the wide application of iron oxide nanoparticles (IONPs), little is known about the specific mechanism of their nephrotoxic effect. We aimed to evaluate the nephrotoxic effects of iron oxide nanoparticles (IONPs) in vivo and the protective effect of ellagic acid (EA) as a silent information regulator sirtuin 1 (SIRT1) activator against the induced nephrotoxicity. Forty male albino Wistar rats were randomly distributed into four equal groups (10 rats each): the control group (oral saline for 30days), ellagic acid (EA) group (10mg/kg b.w. EA, orally for 30days), IONP group (20mg/kg b.w. IONP I/P injection at the 24th-30th day), and EA + IONP group (10mg/kg b.w./day EA for 30days + 20mg/kg b.w. IONPs at the 24th-30th day). In the present study, the potent antioxidant and antiapoptotic effects of EA were indicated by the significant overexpression of SIRT1 in renal tissues that leads to significant decreases in renal MDA content, P53 protein level and forkhead-box transcription factor1 (FOXO1) expression, and significant increases in renal GSH level, catalase activity, growth arrest and DNA damage-inducible protein 45 alpha (GADDα45), and renal inhibition of apoptosis protein (KIAP) gene expression levels in the EA + IONP-treated group. These results were confirmed by the improved histopathological renal features with EA administration. In conclusion, the present study provides the first evidence for the usefulness of EA as a sirtuin1 activator in the prevention or treatment of renal damage. Thus, EA could be used as a promising therapy for the prevention of IONP-induced nephrotoxicity.

The activity of Terminalia chebula Retz. extract on doxorubicin-induced renal damage in rats

Context: Doxorubicin (DXR) is a common anticancer drug known to produce several complications. Terminalia chebula popularly known as ‘King of medicine’ is found to possess wound healing, anti-inflammatory and antioxidant properties. Aims: To evaluate the effects of Terminalia chebula extract on doxorubicin-induced renal damages in rats. Methods: Coadministration of Terminalia chebula extract (0.25, 0.5 and 1.0 g/kg) was tested against DXR (2.5 mg/kg) induced renal damages in rats. Additional two groups were evaluated by administering 0.5 g/kg of the extract to animals either before or after DXR treatment. Kidney function tests were performed by measuring the serum levels of urea, creatinine, uric acid, and total protein. The antioxidant activity of the extract was evaluated by in vivo and in vitro methods. Histopathology of kidney tissues was performed to assess the morphological changes. The significance of results obtained were statistically analyzed. Results: The data obtained indicated that co-administration of the extract at higher doses (0.5 and 1.0 g/kg) significantly (p<0.01) reduces the serum levels of creatinine, urea, uric acid, and total proteins compared to DXR group. The extract also decreases the structural damages induced by DXR and exhibited antioxidant property. However, the pre- and post-treatments of Terminalia extract neither alter significantly the biomarker levels nor ameliorated the histopathological changes induced by DXR in rats. Conclusions: The observations indicated that co-administration of Terminalia chebula decreased the renal damage induced by DXR in rats. The protective action of the extract may be related to its wound-healing and antioxidant properties, the latter of which diminished the free-radical damage induced by DXR.

LncRNA-Gm4419 alleviates renal damage in rats with diabetic nephropathy through NF-κB pathway.

lncRNA-Gm4419 alleviates renal damage in rats with diabetic nephropathy through NF-κB pathway.

Renoprotective Effect of Sulphate Polysaccharide from Brown Algae on Ethylene Glycol-Induced Renal Damage in Rats

Renoprotective Effect of Sulphate Polysaccharide from Brown Algae on Ethylene Glycol-Induced Renal Damage in Rats

Renoprotective effect of Corallocarpus epigaea in Nephropathy in Wistar Rats

The renoprotective effect of standardized hydroalcoholic extract of Corallocarpus epigaea was evaluated against cisplatin induced nephrotoxicity. The evaluation was performed on 36 Male Wistar rats. The acute toxicity study was performed in accordance with OECD 425 guidelines. Considering the safety of the extract the screening was done at three dose levels of 100, 200, 400mg/kg. The study was carried for period of 15 days. Vitamin E (100mg/kg) was used as a Standard nephroprotective agent. The kidney function test like serum uric acid, creatinine, albumin, (BUN) was performed. Oxidative stress studies like superoxide dismutase, malondialdehyde activity along with histopathological examination of kidneys was also conducted. Serum creatinine and Urea were elevated in Cisplatin treated group. Decrease in serum albumin was noted in cisplatin control as compared to normal control. Corallocarpus epigaea (100, 200, 400mg/kg) and Vitamin E (100mg/kg) decreased the serum creatinine and BUN and increased the serum albumin level. Decrease in activity of superoxide dismutase was observed in the Cisplatin group as compared to control. Corallocarpus epigaea (100, 200, 400mg/kg) and Vitamin E (100mg/kg) increased superoxide dismutase levels and decreased malondialdehyde levels as compared to Cisplatin group. Histopathological examination of the kidneys revealed the amelioration of Cisplatin induced renal tubular necrosis. Dose dependant increase in the activity was observed. Present investigation revealed that Corallocarpus epigaea resulted in attenuation of Cisplatin induced renal damage in rats.

Protective Effects of Grape Seed Proanthocyanidins on the Kidneys of Diabetic Rats through the Nrf2 Signalling Pathway.

Background Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. Grape seed proanthocyanidin extract (GSPE) is a powerful antioxidant that is believed to protect the kidney through antioxidant action. However, the underlying mechanism of GSPE protection against DN remains unclear. Objective To explore if GSPE can improve DN by activating nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response element signalling and to clarify its possible mechanism. Materials and methods. Ten healthy Sprague-Dawley rats were randomly selected as controls. Rats with streptozotocin-induced diabetes were randomly divided into three groups (10 animals/group): type 2 diabetes mellitus (T2DM) group (untreated), L-GSPE group (treated with 125-mg/kg/day GSPE for 8 weeks), and H-GSPE group (treated with 250 mg/kg/day GSPE for 8 weeks). Results Renal histopathological results indicated limited pathological damage in GSPE-treated groups. Compared with the T2DM group, the H-GSPE group had significantly reduced kidney weight and renal index. Similarly, the levels of fasting blood glucose, serum creatinine, blood urea nitrogen, uric acid, urinary albumin, and renal malondialdehyde (p < 0.05) were also significantly decreased. In addition, GSPE significantly increased the levels of superoxide dismutase, total antioxidative capability, and glutathione (p < 0.05) as well as the protein levels of Nrf2, HO-1, glutathione S-transferase, and NAD (P)H quinone oxidoreductase 1 (p < 0.05). Conclusion The results indicate that GSPE reduced renal damage in rats with diabetes by activating the Nrf2 signalling pathway, which consequently increased the antioxidant capacity of the tissue. Therefore, GSPE is a potential natural agent for the treatment of diabetic nephropathy.

Nephroprotective activity of Sinapis alba in gentamicin induced murine model of renotoxicity

Sinapis alba, belongs to the family Brassicaceae and is known to possess an antioxidant capacity. Based on this background, this study was planned to look for the nephroprotective activity of Sinapis alba seed extract against nephrotoxicity caused by gentamicin in rats. Sinapis alba seeds were dried in the shade and then powdered. Then, the powder was subjected to extraction with 95% ethanol and brought to a syrup consistency by distilling the solvent and reducing the pressure using a water bath. Animals were divided into four groups. Each group had six animals in it. Group 1 serves as normal control, while the next group was disease control (received gentamicin). The rats in third and fourth groups were treated with the extract of Sinapis alba (200 and 400 mg/kg). The animals were sacrificed, and biochemical and histopathological studies were carried out after the 8th day of study. Results of the study showed positive effects with 200 mg/kg as well as 400 mg/kg doses of Sinapis alba extract. Serum urea, creatinine, and BUN was reduced significantly in the test group compared to the group which received gentamicin (p&lt;0.05). Moreover, this biochemical evidence was also validated with the histopathological results indicated with the absence of necrosis and casts in the tubular lumen. Ethanolic extract of Sinapis alba administered by the oral route in an experimental murine model using gentamicin as an instigator of damage to the kidney, effectively reduced renal damage in rats, therefore provides a scientific evidence of a renoprotective effect.

Liraglutide protects from renal damage via Akt-mTOR pathway in rats with diabetic kidney disease.

To explore the protective effect of liraglutide on renal damage in rats with diabetic kidney disease (DKD) through the protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. A total of 45 specific pathogen-free male Sprague-Dawley rats were divided into healthy group (no diabetes, n=15), diabetes group (diabetes, n=15), and liraglutide group (diabetes + liraglutide intervention, n=15). The differences in the biochemical indexes, lesion degree, glomerular Nephrin expression level, and mRNA and protein expressions of Akt-mTOR in renal tissues were detected in three groups via hematoxylin-eosin (HE) staining, immunohistochemistry, Western blotting, and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), respectively. The albumin-to-creatinine ratio (ACR) and levels of serum creatinine (Scr), urine microalbumin (UmAlb), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) in renal tissues were the lowest in healthy group and the highest in diabetes group, while they significantly declined in liraglutide group compared with those in diabetes group. Also, there were statistically significant differences (p<0.05). The level of high-density lipoprotein cholesterol (HDL-C) in renal tissues was the highest in healthy group and the lowest in diabetes group, while it was significantly increased in liraglutide group compared with that in diabetes group. Also, there were statistically significant differences (p<0.05). In healthy group, the mesangial structure and renal tubules were normal, the tubular basement membrane was smooth and intact, and there were no interstitial widening and inflammatory cell infiltration. Compared with diabetes group, the mesangial cell proliferation and vacuolar degeneration were alleviated, while the tubular dilatation or atrophy, fibrous tissues, and inflammatory cells were reduced in liraglutide group. Moreover, the results of immunohistochemical staining revealed that the glomerular Nephrin protein was arranged uniformly and showed the blue-black particles in healthy group. The glomerular Nephrin protein expressed was significantly decreased and arranged disorderly in diabetes group compared with that in healthy group, while it was increased in liraglutide group compared with that in diabetes group (p<0.05). The protein expression of Akt-mTOR in renal tissues was the lowest in healthy group and the highest in diabetes group, while it markedly declined in liraglutide group compared with that in diabetes group, displaying statistically significant differences (p<0.05). Similarly, the mRNA expression of Akt-mTOR in renal tissues was the lowest in healthy group and the highest in diabetes group, while it markedly declined in liraglutide group compared with that in diabetes group, displaying also statistically significant differences (p<0.05). Liraglutide can significantly reduce the blood glucose and improve the renal function in rats by suppressing the protein expression of AKT-mTOR, thereby exerting a protective effect on renal damage in rats with DKD.

The therapeutic impact of entresto on protecting against cardiorenal syndrome-associated renal damage in rats on high protein diet

Background: This study tested the hypothesis that Entresto could safely and effectively preserve heart and kidney function in rats with cardiorenal syndrome (CRS) induced by 5/6 nephrectomy and intra-peritoneal doxorubicin administration (accumulated dosage up to 7.5 mg/kg) together with daily high-protein-diet (HPD).Methods and Results: Adult male Sprague-Dawley rats (n = 24) were equally categorized into Group 1 (sham-operated control + HPD), Group 2 (CRS + HPD) and Group 3 [CRS + HPD + Entresto (100 mg/kg/day orally) since Day 14 after CRS induction] and euthanized by Day 63 after CRS induction. By Day 63, circulatory BUN and creatinine levels and ratios of urine protein to creatinine were significantly higher in Group 2 than those in Groups 1 and 3, and significantly higher in Group 3 than in Group 1, whereas left-ventricular ejection fraction and kidney weight showed an opposite pattern among all groups (all p < 0.001). Microscopically, fibrosis area and intensity of oxidative stress (i.e., DCFDA stain) in kidney/heart tissues exhibited a pattern identical to that of creatinine level among all groups (all p < 0.0001). Kidney injury score and protein expressions of autophagy (i.e., beclin-1/Atg-5/protein ratio of LC3-BII/LC3-BI), fibrosis (Smad3/TGF-ß), apoptosis (mitochondrial-Bax/capase2/3/9), oxidative-stress (NOX-4/oxidized protein/xanthine-oxidase/catalase), membranous p47phox phosphorylation and mitochondrial-damage biomarker (cytosolic-cytochrome-C) were higher in Group 2 than those in Groups 1 and 3, and significantly higher in Group 3 than in Group 1, while protein expressions of anti-apoptosis (Bcl-2/Bcl-XL) and mitochondrial integrity (mitochondrial-cytochrome-C) markers displayed an opposite pattern among all groups in kidney tissues (all p < 0.0001).Conclusion: Oral administration of entresto was safe and could offer protection against CRS-induced heart and kidney damage.

Nephroprotective properties of the methanol stem extract of Abrus precatorius on gentamicin‐induced renal damage through suppression of NF‐κB/CRP and enhancement of Bcl‐2 signaling pathways

The nephroprotective properties of methanol stem bark extract of Abrus precatorius against gentamicin‐induced renal damage in rats was evaluated in this study. Thirty (30) male Wistar rats were divided into five equal groups. Group A was the negative control group while B was the positive control group which received gentamicin 100 mg/kg intra‐peritoneally for six days. Group C were pretreated with 100 mg/kg extract for the three days and then concurrently with gentamicin 100 mg/kg for three days and group D were pretreated with 200 mg/kg extract for three days and then concurrently with gentamicin 100mg/kg for three days. Group E received gentamicin intraperitoneally for six days followed by administration of 200 mg/kg of the extract for 3 days. Blood samples, kidneys and kidney homogenates were collected for haematological, biochemical, histopathological and immunohistochemical analysis. The results showed that no significant haematological changes were noted. The groups treated with extract exhibited significant increase in body weight gain. While group B significantly exhibited focal areas of inflammation, fatty degeneration, congestion of vessels, tubular necrosis and glomerular atrophy, the lesions were mild with the treated groups. Treated groups exhibited a dose dependent significant decrease in serum creatinine, urea, XO, NO and Myeloperoxidase, AOPP, Protein carbonyl, H2O2, MDA levels when compared with gentamicin treatment group. There were significant dose dependent improvements in SOD, GST, GSH, Protein thiol, and non‐protein thiol levels in the treated groups when compared with group B. In immunohistochemistry, gentamicin treatment group exhibited over expression of CRP and NF‐κB levels, and marked reduction in expression of Bcl‐2 while the reverse was seen in the groups treated with methanol extracts of Abrus precatorius.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

NEPHROPROTECTIVE ACTIVITY OF PLUMERIA RUBRA AGAINST CISPLATIN INDUCED NEPHROTOXICITY IN EXPERIMENTAL RATS

Objective: The current study was designed to evaluate the protective effect of standardized hydroalcoholic extract of Plumeria rubra (HAEPR) against cisplatin-induced nephrotoxicity in Wistar rats. &#x0D; Methods: HAEPR was administered orally at 3 dose levels (100,200,400 mg/kg). Vitamin E (250 mg/kg) was used as a Standard nephroprotective agent. The kidney function test (estimation of serum creatinine, albumin, blood urea nitrogen) oxidative stress study (estimation of superoxide dismutase, malondialdehyde activity) and histological examination of kidneys was conducted.&#x0D; Results: The efficacy of HAEPR was compared with Cisplatin (CP) treated group. Serum creatinine and BUN was significantly (p&lt;0.01) elevated in CP-treated group compared to the control group. HAEPR (100,200 mg/kg) and Vitamin E (250 mg/kg) significantly (p&lt;0.01) decreased the serum creatinine and BUN levels. CP treated group exhibited significant (p&lt;0.01) decrease in albumin when compared to control. Significant (p&lt;0.01) increase in the serum albumin level was found in HAEPR (100,200 mg/kg) and Vitamin E (250 mg/kg) compared to CP group. Significant (p&lt;0.01) decrease in the activity of SOD was observed in the CP group as compared to control. HAEPR (100 and 200 mg/kg) and Vitamin E (250 mg/kg) significantly (p&lt;0.01) increased SOD levels. HAEPR (400 mg/kg) significantly (p&lt;0.05) increased SOD levels. HAEPR (100,200,400 mg/kg) significantly (p&lt;0.01) decreased MDA levels as compared to CP group. Histopathological examination of the kidneys showed that HAEPR markedly ameliorated Cisplatin-induced renal tubular necrosis. An extract was found effective at all doses, although low dose (100 mg/kg) was found to be more effective and comparable with the standard group (Vitamin E 250 mg/kg). &#x0D; Conclusion: Present investigation revealed that HAEPR resulted in attenuation of Cisplatin-induced renal damage in rats.

RETRACTED ARTICLE: Sulforaphane potentially attenuates arsenic-induced nephrotoxicity via the PI3K/Akt/Nrf2 pathway in albino Wistar rats

Oxidative stress plays a significant role in the pathophysiology of numerous kidney diseases, generally mediated by reactive oxygen species (ROS). Arsenic (Ar) is known to exert its toxicity through the generation of ROS and inflammation. The current study investigates the protective effects of sulforaphane (SFN) against arsenic-induced renal damage via PI3K/Akt-mediated Nrf2 pathway signaling. Thirty-two male albino Wistar rats were randomly divided into four groups of eight animals each, designated as control, arsenic (Ar), sulforaphane plus Ar (SFN+Ar), and sulforaphane alone (SFN), with oral administration of Ar (5 mg/kg BW) and SFN (80 mg/kg BW) daily for 28 days. Ar administration significantly (P < 0.05) increased the levels of ROS, OHdG, Ar accumulation, and lipid peroxidation, and decreased levels of enzymatic and nonenzymatic antioxidants. Notably, a significant (P < 0.05) increase was observed in markers of apoptosis, DNA damage, TUNEL-positive cells, and dark staining of ICAM-1 in renal tissue with decreased PI3K/Akt/Nrf2 gene expression. The biochemical findings were supported by histopathological and electron microscopy evaluation, which showed severe renal damage in rats treated with Ar. Pretreatment with SFN significantly (P < 0.05) attenuated renal ROS, OHdG, lipid peroxidation, and DNA damage, and increased phase II antioxidants via PI3K/Akt-mediated Nrf2 activation in renal tissue. These results show that dietary supplementation with SFN protects against Ar-induced nephrotoxicity via the PI3K/Akt-mediated Nrf2 signaling pathway in the rat kidney.

RESCUE OF INFLAMMATORY RENAL DAMAGE BY MEDICINAL PLANT EXTRACTS IN DIABETIC RATS

Diabetic nephropathy (DN) is the most critical diabetic complication that leads to renal failure. The purpose of this research was to explore the anti-diabetic effectiveness of Cucumis melo var. flexuosus and/or Phoenix dactylifera fruit aqueous extracts and their mechanisms in alleviating nephropathy in hyperglycemic rats. Diabetes was promoted in rats by injection (i.p.) of a single dose of streptozotocin (STZ). C. flexuosus and P. dactylifera extracts (CFE and PDE respectively) were ingested to diabetic rats for thirty consecutive days. The data revealed that intake of either plant extract or their combination to diabetic rats, significantly diminished the serum glucose and raised the serum insulin concentration. The plant extracts significantly ameliorated the increases in relative kidney weights as well as in renal tumor necrosis factor (TNF-α), serum C –reactive protein (CRP) and renal vascular endothelial factor (VEGF). Serum kidney function markers (creatinine, uric acid and urea) were also decreased in diabetic rats treated with the plant extracts. Histopathological observation was also carried out to confirm the biochemical results. This study has proven that the current plant extracts have potential hypoglycemic effect and could attenuate diabetic inflammatory renal damage in rats. The combination of the two extracts was synergistically the effective one. This result may help in exploring a novel therapy to manage diabetes and its complications.

Role of Salvia officinal's Silver Nanoparticles in Attenuating Renal Damage in Rats Exposed to Methotrexate(Part I)

The aim of the present study was to investigate the protective role of Salvia officinal's silver nanoparticles as antioxidant on nephrotic damage induced by methotrexate in adult rats. Green silver nanoparticles were synthesized using alcoholic extract of salvia officinal's leaves, and were characterized by UV-spectrophotometry and scanning electron microscope. The mixing of the plant extract of Salvia. officinal's with silver nitrate solution (1mM), lead to changing of the reaction mixture color to yellowish within one hour and to dark brown after 8 hours, indicating the generation of Salvia officinal's silver nanoparticles , due to the reduction of silver metal ions silver (Ag+) into Nano silver particles via the active compounds present in the S. officinal's plant extracts. Changing in color after the reduction of Ag+ to Salvia officinal's silver nanoparticles. The reduction rate and formation of nanoparticles can be increased further by increase in incubation time. Silver nitrate conversion to Nano silver particles was found to be successful as suggested by the change in color of the solution to brown. For studying the protective role of Salvia officinal's silver nanoparticles , twenty eight adult Wister albino rats were randomly assigned and divided in to four groups as follows T1, T2, T3, and T4, They were treated intramuscularly (twice per week) for 45 days as follows; T1:animals in this group, were given Salvia officinal's (150mg /Kg/.B.W), T2: animals in this groups were given Salvia officinal's Silver nanoparticles (150mg/Kg B.W.); T3:animals of this groups were given both Methotrexate (0.25mg/kg/ B.W.) and Salvia officinal's silver nanoparticles (150mg/Kg/B.W); T4: animals in this groups were given methotrexate (0.25mg/Kg B.W.) for 45 days . The animals of all groups were considered as control group at day zero and injected only doubled distilled water Intramuscala. Fasting blood samples were collected at 0, 15, 30 and 45 days of experimental periods from anesthetized rats using retro-orbital sinus technique and cardiac puncture technique, then sera was isolated for measuring: malondialdehyde, glutathione in serum, creatinine, and blood urea nitrogen and uric acid concentrations. The results showed that animals received methotrexate (group T4) caused a case of oxidative stress manifested by significant decrease grower in , elevation in malondialdehyde concentrations, renal dysfunction as documented by significant elevation in serum creatinine, urea and uric acid concentrations. On the other hand, the protective role of salvia officinal's and Salvia officinal's silver nanoparticles given concurrently with methotrexate was clarified in groups T2and T3 ,where there was alleviation of renal damage through correction of the previous mentioned parameters and correction of antioxidant status. In conclusion, the current study documented the antioxidant activity and reno protective effects of Salvia officinal's silver nanoparticles against damaging effects of methotrexate in rats.