Renal Enzyme Activity Research Articles

The potential role of upregulated PARP-1/RIPK1 expressions in amikacin-induced oxidative damage and nephrotoxicity in Wistar rats.

This study aimed to investigate the gene expression levels associated with nephrotoxic action of amikacin, as well as the post-treatment effect of diuretics on its nephrotoxic effects. Sixty male rats were divided equally into six groups, including the control group receiving saline intra-peritoneally (ip), and the five treated groups including therapeutic and double therapeutic dose groups, injected ip (15 and 30mg/kg b.wt./day) respectively for seven days, and another two rat groups treated as therapeutic and double therapeutic dose groups then administered the diuretic orally for seven days and the last group received amikacin ip at a rate of 15mg/kg/day for seven days, then given free access to water without diuretics for another seven days and was kept as a self-recovery group. Amikacin caused kidney injury, which was exacerbated by the double therapeutic dose, as evidenced by abnormal serum renal injury biomarkers, elevated renal MDA levels, inhibition of renal catalase and SOD enzyme activities, with renal degenerative and necrotic changes. Moreover, comet assays also revealed renal DNA damage. Interestingly, amikacin administration markedly elevated expression levels of the PARP-1, RIP1, TNF-α, IL-1β, and iNOS genes as compared to the control group. However, compared to the self-recovery group, post-amikacin diuretic treatment modulates amikacin-induced altered findings and alleviates amikacin nephrotoxic effects more efficiently. Our findings suggested the potential role of PARP-1 and RIPK1 expressions that influence the expression of proinflammatory cytokines such as IL-1β and TNF-α by exaggerating oxidative stress which may contribute to the pathogenesis of amikacin-induced nephrotoxicity.

Protective effects of limb remote ischemic per-conditioning on the heart injury induced by renal ischemic-reperfusion through the interaction of the apelin with the RAS/iNOS pathway.

Remote ischemic conditioning upregulates endogenous protective pathways in response to ischemia-reperfusion injury. This study tested the hypothesis that limb remote ischemic per- conditioning (RIPerC) exerts cardioprotective effects via the renin-angiotensin system (RAS)/inducible nitric oxide synthase (iNOS)/apelin pathway. Renal ischemia-reperfusion injury (I/R) was induced by bilateral occlusion of the renal pedicles for 60 minutes, followed by 24 hours of reperfusion; sham-operated rats served as controls. RIPerC was induced by four cycles (5 minutes) of limb ischemia-reperfusion along with bilateral renal ischemia. The functional disturbance was evaluated by renal (BUN and creatinine) and cardiac (troponin I and lactate dehydrogenase) injury biomarkers. Renal I/R injury increased renal and cardiac injury biomarkers that were reduced in the RIPerC group. Histopathological findings of the kidney and heart were also suggestive of amelioration injury-induced changes in the RIPerC group. Assessment of cardiac electrophysiology revealed that RIPerC ameliorated the decline in P wave duration without significantly affecting other cardiac electrophysiological changes. Further, renal I/R injury increased the plasma (322.40±34.01 IU/L), renal (8.27±1.10 mIU/mg of Protein), and cardiac (68.28±10.28 mIU/mg of protein) angiotensin-converting enzyme (ACE) activities in association with elevations in the plasma and urine nitrite (25.47±2.01 & 16.62±3.05 μmol/L) and nitrate (15.47±1.33 & 5.01±0.96 μmol/L) levels; these changes were reversed by RIPerC. Further, renal ischemia-reperfusion injury significantly (P=0.047) decreased the renal (but not cardiac) apelin mRNA expression, while renal and cardiac ACE2 (P<0.05) and iNOS (P=0.043) mRNA expressions were significantly increased compared to the sham group; these effects were largely reversed by RIPerC. Our results indicated that RIPerC protects the heart against renal ischemia- reperfusion injury, likely via interaction of the apelin with the RAS/iNOS pathway.

#5878 PROTECTIVE EFFECTS OF VITAMIN D ON HYPERANDROGENEMIA-INDUCED-ACUTE KIDNEY INJURY THROUGH THE INTERACTION WITH THE RAS/INOS PATHWAY

Abstract Background and Aims The onset and development of metabolic abnormalities are closely related to polycystic ovary syndrome (PCOS). It has not yet been determined whether PCOS contributes to kidney injury, and the mechanism underlying the condition is not fully understood. Treatment with vitamin D has been shown to have beneficial effects on women with PCOS and renal disease. This study investigated the hypothesis that vitamin D supplementation exerts renoprotective effects via regulating the renin-angiotensin system (RAS)/inducible nitric oxide synthase (iNOS) pathway Method Female Sprague-Dawley rats were randomly divided into five groups (n = 10): (a) control, (b) sham, (c) dehydroepiandrosterone (DHEA, 6 mg/100 g day-1 S.Q.), (d) DHEA + vitamin D (1000 IU/Kg; 3 days/week), and (e) vitamin D. Plasma, ovary, and kidney levels of angiotensin-converting enzyme (ACE) activity was determined using FAPGG-based colorimetric method. The amount of NO was measured by determining the concentrations of nitrite and nitrate end products in the plasma and tissue samples using the Griess method. Histopathological changes in the ovary and kidney were also evaluated. Results Plasma testosterone increased in DHEA-treated rats compared with controls, indicating a hyperandrogenic state. Further, hyperandrogenemia-induced-acute kidney injury increased the plasma, renal, and ovarian angiotensin-converting enzyme (ACE) activities in association with elevations in the plasma and urine nitrite and nitrate levels; these changes were reversed by vitamin D treatment. Conclusion Hyperandrogenemia causes systemic abnormalities through RAS imbalance and NO metabolism disturbances, followed by apparent destruction of renal and ovarian tissues. Vitamin D supplementation attenuated these hyperandrogenemia-associated acute kidney injuries, likely via interaction with the RAS/iNOS pathway.

“In vivo” free radical scavenging efficacy of beebread against biochemical alterations induced by Salmonella enterica serovar Typhimurium

Salmonella typhimurium induced hepatic and renal toxicity was investigated using standard laboratory techniques in mice. BALB/c mice were divided into ten groups (8 mice per group). Group (Gp) 1 served as normal, and were administrated with normal saline orally, and Gp2 served as infected, and were injected bacteria (2×104 CFU/mL) only, while Gp3, 5, 7 and, 9 were administrated beebread (250 mg/kg body weight) of Helianthus annus, Brassica campestris, Zea mays and vitamin C respectively for 21 days without Salmonella infection, and Gp 4, 6, 8 and, 10 were administrated beebread (250 mg/kg bw) of Helianthus annus, Brassica campestris, Zea mays and vitamin C respectively for 21 days with a bacterial infection. Serum activities of hepatic and renal enzymes were analysed. A significant increase was observed in biochemical enzymes in Salmonella infected group on the 5th day but after the administration of beebread of different crops, relief was observed to be near normal. This alleviation was more with beebread of Helianthus annus. Furthermore, administration of beebread without bacteria did not show any negative effects in mice. Thus, the results indicate that aqueous extract of beebread of different crops is safe and can be exploited in healthcare delivery systems.

Intervention effects of drugs on GSH and SOD enzyme activity of rats kidney acutely poisoned by nickel carbonyl

Objective: To evaluate the intervention effect of various drugs on glutathione (GSH) and superoxide dismutase (SOD) enzyme activity of rats kidney with acute nickel carbonyl poisoning. Methods: In January 2019, The 250 SPF male SD rats were randomly divided into normal control group (n=10) , poisoned group (n=40) and treatment groups (n=200) according to the random number table method. And the treatment groups were divided into methylprednisolone group (20 mg/kg) , DDC group (100 mg/kg) , sodium selenite group (10 μmol/kg) , Shenfu huiyang decoction group (0.25 ml) and methylprednisolone combined with DDC group (100 mg/kg) , with 40 mice in each group. Except for the normal control group, rats in the other groups were exposed to nickel carbonyl for 30 min, at 4 h and 30 h after exposure, the rats in each treatment group were intraperitoneally injected with corresponding drugs, and kidney tissues were collected 3 d and 7 d after administration, with 10 mice in each group. The activities of GSH and SOD in kidney were measured by enzyme-linked immunosorbent assay, and using electron microscopy observe ultrastructure changes. Results: Compared to the control group, the activities of GSH and SOD enzyme of poisoned group were significantly decreased at 3 d or 7 d after 4 h or 30 h exposure, and the difference was statistically significant (P=0.000, 0.031, 0.001, 0.033) , the epithelial nuclei of proximal convoluted tubules were pyknosis and lysosome hyperplasia in the cytoplasm. And compared to poisoned group, the activities of GSH and SOD enzyme of methylprednisolone+DDC group were significantly increased at treatment with 7 d after 4 h exposure, the difference was statistically significant (P=0.022, 0.000) , and the activities of GSH and SOD enzyme of methylprednisolone and enzyme of methylprednisolone+DDC group were significantly higher at 7 days than at 3 days, the difference was statistically significant (P=0.020, 0.017, 0.018, 0.033) . The results of electron microscopy showed that the cell nuclei and cytoplasmic organelles of proximal convolute tubule were almost restored to normal tissue level of both methylprednisolone group and methylprednisolone+DDC group. Conclusion: The methylprednisolone and methylprednisolone+DDC have obvious repair effect on renal enzyme activity level of rats with acute nickel carbonyl poisoning, and the treatment effect is better for a long time of medication.

Therapeutic Efficacy of Natural Product 'C-Phycocyanin' in Alleviating Streptozotocin-Induced Diabetes via the Inhibition of Glycation Reaction in Rats.

Diabetes is a long-term metabolic disorder characterized by persistently elevated blood sugar levels. Chronic hyperglycemia enhances glucose-protein interactions, leading to the formation of advanced glycation end products (AGEs), which form irreversible cross-links with a wide variety of macromolecules, and accumulate rapidly in the body tissues. Thus, the objective of this study was to assess the therapeutic properties of C-phycocyanin (C-PC) obtained from Plectonema species against oxidative stress, glycation, and type 2 diabetes mellitus (T2DM) in a streptozotocin (STZ)-induced diabetic Wistar rat. Forty-five days of C-PC administration decreased levels of triglycerides (TGs), blood glucose, glycosylated hemoglobin, (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), liver and kidney function indices, and raised body weight in diabetic rats. C-PC suppressed biochemical glycation markers, as well as serum carboxymethyllysine (CML) and fluorescent AGEs. Additionally, C-PC maintained the redox state by lowering lipid peroxidation and protein-bound carbonyl content (CC), enhancing the activity of high-density lipoprotein cholesterol (HDL-C) and renal antioxidant enzymes, and preserving retinal and renal histopathological characteristics. Thus, we infer that C-PC possesses antidiabetic and antiglycation effects in diabetic rats. C-PC may also act as an antidiabetic and antiglycation agent in vivo that may reduce the risk of secondary diabetic complications.

Tissue-specific differences and temperature-dependent changes in Na,K-ATPase of the roach (Rutilus rutilus)

Na,K-ATPase activity is vital for virtually all cells of the animal body and the major consumer of cellular energy. However, Na,K-ATPase activity, the number of Na+ pump units, the catalytic rate of the pump, and their responses to thermal acclimation in different tissues of the same fish species have been seldom measured. Therefore, roach (Rutilus rutilus), eurythermal freshwater fish, was acclimated at 4 °C (cold-acclimated, CA) and 18 °C (warm-acclimated, WA), and the Na+ pump density and the temperature-dependence of Na,K-ATPase activity were determined in the heart, gills, kidney and brain. There were prominent tissues specific differences in Na,K-ATPase activity. The activity was highest in the brain (100%), whereas the activity of renal, branchial and cardiac enzymes was 55%, 9%, and 4% of the brain activity in the WA roach at 25 °C. The corresponding values for brain, kidney, gills and heart of the CA fish at 25 °C were 100%, 56%, 5% and 4%, respectively. The number of Na,K-ATPase α-subunits, determined by [3H]ouabain binding, strongly correlated with the Na,K-ATPase activity at R2 values of 0.99 and 0.85 for WA and CA fish, respectively. Acclimation to cold, increased the number of Na,K-ATPase α-subunits in the heart, kidney and brain (P < 0.05), but this did not appear as an increase in Na,K-ATPase activity. In the gills, Na,K-ATPase α-subunits did not change in cold-acclimation, but Na,K-ATPase activity was depressed. Although tissue-specific differences in Na,K-ATPase activity are largely determined by the density of α-subunits, differences in Na,K-ATPase activity within the same tissue due to temperature acclimation involve also other factors in addition to the number of Na+ pump units.

Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function.

The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys are still understudied. We investigated whether fructose and/or chronic unpredictable stress modulate copper metabolism in a way that affects redox homeostasis, thus contributing to progression of metabolic disturbances in the kidney. We determined protein level of copper transporters, chaperones, and cuproenzymes including cytochrome c oxidase, as well as antioxidant enzymes function in the kidneys of male Wistar rats subjected to 20% liquid fructose supplementation and/or chronic stress. Liquid fructose supplementation increased level of copper chaperone of superoxide dismutase and decreased metallothionein level, while rendering the level of copper importer and copper chaperones involved in copper delivery to mitochondria and trans Golgi network unaffected. Stress had no effect on renal copper metabolism. The activity and expression of renal antioxidant enzymes remained unaltered in all experimental groups. In conclusion, fructose, independently of stress, decreased renal copper level, and modulated renal copper metabolism as to preserve vital cellular function including mitochondrial energy production and antioxidative defense, at the expense of intracellular copper storage.

Urinary N-Acetyl-β-d-glucosaminidase (uNAG) as an Indicative Biomarker of Early Diabetic Nephropathy in Patients with Diabetes Mellitus (T1DM, T2DM): A Systematic Review and Meta-Analysis

Diabetic nephropathy (DN) is the main cause of chronic kidney disease in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Renal tubular lysosomal enzyme activities like N-acetyl-β-d-glucosaminidase (NAG) have been shown to increase in patients developing DN. The aim of this systematic review and meta-analysis is to evaluate the diagnostic accuracy of NAG, as a preventional biomarker in the early stages of DN in patients with diabetes mellitus. Two impartial reviewers conducted a complete PubMed search until July 2021. A 2 × 2 contingency table was created for each trial and sensitivity and specificity were estimated using a bivariate random effects model. To pool data and estimate the area under the curve (AUC), the hierarchical summary ROC (hsROC) approach was utilized. Deek’s test was used to estimate publication bias. The meta-analysis included 21 studies that evaluated 2783 patients with T1DM and T2DM, as well as 673 healthy individuals. The AUC of urinary NAG (uNAG) ranged from 0.69 (95% CI: 0.65–0.73) to 0.89 (95% CI: 0.86–0.92). According to the results, NAG in urine can be considered as a potential and effective biomarker for predicting DN in diabetic patients (T1DM, T2DM).

Sub-fractions from Carica Papaya Seed Extracts Can Prevent Potassium Bromate- induced Changes in Activities of Renal Brush Border Membrane Enzymes and Some Enzymes of Carbohydrate Metabolism in the Kidney of Rats

Aim: To investigate the effect of the chromatographic fractions of Carica papaya seed on KBrO3 –induced reduction in the activities of renal brush border membrane (BBM) marker enzymes and the changes in activities of some enzymes of carbohydrate metabolism in the kidney of rats.&#x0D; Study Design: twenty male Wistar rats were divided into four groups, five rats per group; normal control, KBrO3 control, papaya fraction control and KBrO3 group administered with 126mg/kg body weight of the most active fraction of partially purified methanol extract of C. papaya for 48 hours.&#x0D; Place and Duration of Study: Department of Biochemistry Laboratory, Faculty of Basic Medical Sciences, Bayero University Kano, Nigeria.&#x0D; Methodology: The activities of renal BBM marker enzymes: γ-glutamyl transferase, alkaline phosphatase, maltase and leucine aminopeptidase were assayed in homogenates of renal cortex and medulla, and in brush border membrane vesicle (BBMV) isolated from cortex using standard methods. Furthermore, activities of the following enzymes representing different pathways of carbohydrate metabolism were determined in renal homogenates: hexokinase (HK), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), glucose 6-phosphatase (G6P), fructose 1,6-bisphosphatase (FBP), glucose 6-phosphate dehydrogenase (G6PD) and malic enzyme (ME).&#x0D; Results: KBrO3 administration significantly (P&lt;0.05) decreases the activities of all the BBM marker enzymes in renal homogenates and BBMV. It also decreases the activities of MDH, G6P, FBP and G6PD, and significantly increases (P&lt;0.05) that of HK, LDH and ME in renal homogenates however co-administration of most active fraction of C. papaya seed prevented all the KBrO3 -induced changes in these biochemical parameters.&#x0D; Conclusion: Chromatographic fractions of C. papaya seed extract possesses potent phytochemicals that could prevent KBrO3 –induced reduction in activities of renal BBM marker enzymes and the changes in enzymes of carbohydrate metabolism studied and therefore could be analyzed further to isolate the bioactive compounds.

Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

BackgroundMelittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done.ResultsThis study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups.ConclusionsOur study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form.

POTENTIAL RISKS IN MODERN ANTIBIOTIC THERAPY

Knowledge of the safety profile of antibacterial drugs is important for rational pharmacotherapy with antibiotics. The purpose of this information is to help the doctor, pharmacist and patient to (quickly) "navigate" in the safety of antibiotics to implement one of the basic principles of pharmacotherapy "Do no harm!". The aim of the study. Analysis of possible potential risks in modern antibiotic therapy. Materials and methods. Analysis of data from the scientific literature on the side effects of antibiotics. Results. Most antibiotics have a wide spectrum of antimicrobial action, much less of them have a narrow spectrum of activity, but all of them have side effects (SE). In particular, the neurotoxicity of penicillins and fluoroquinolones is a consequence of their antagonism with GABA. The latter mechanism is also responsible for the neurotoxicity of carbapenens, monobactams and cephalosporins. Cardiotoxicity and hematotoxicity of benzylpenicillins are the result of inhibition of tissue respiration and the process of converting fibrinogen to fibrin, which causes bleeding. The hematotoxicity of carbopenicillins, monobactams and cephalosporins is associated with the inhibition of the conversion of vicasol (vit. K) into its active form, as well as the obstruction of its synthesis due to the suppression of normal intestinal microflora (the main producer of endogenous vit. K). The nephrotoxicity of aminoglycosides and vancomycin is associated with the accumulation of these drugs in the cells of the proximal renal tubules and impaired enzyme activity (Na+-, K+-, ATP; respiratory, etc.), which leads to interstitial nephritis. Ototoxicity of antibiotics is observed when they are used over the age of 60 – a factor that predisposes to ototoxicity. Conclusions. In order to conduct effective antibiotic therapy, it is very important to take into account the side effects that are characteristic of certain groups of antibiotics and each is representatively individual.

Study of the Functional State of the Proximal Renal Tubules in Patients with Asymptomatic Chronic Heart Failure in Dyslipidemia and its Correction with Simvastatin Treatment

Aim. To study indicators of epithelial dysfunction in the proximal renal tubules by determining the activity of organ-specific enzymes neutral α-glucosidase (NAG) and L-alanine aminopeptidase (LAAP), in patients with the initial stage of chronic heart failure in dyslipidemia, and the possibility of reducing with simvastatin.Material and methods. The study involved 90 subjects, who were divided into control and main groups. The control group consisted of 30 practically healthy individuals, the main group was divided into 2 subgroups: patients with stage I chronic heart failure (CHF) without type 2 diabetes mellitus (DM2) and patients with CHF with DM2. Patients of each of the main subgroups received simvastatin 20-40 mg/day in addition to treatment of the main pathology. The main group included patients with a total serum cholesterol level of more than 6.0 mmol/l, a BMI level of more than 30 kg/m2, and who had not previously taken statins. The exclusion criterion was a violation of the filtration capacity of the kidneys and the presence of gross dysfunction of organs and systems of the body. The functional state of the proximal renal tubules was assessed by the concentration of NAG and LAAP in dialized urine.Results. Initially, the level of activity of renal enzymes in representatives of both major subgroups is higher than the group of practically healthy individuals. Taking simvastatin in the CHF without DM2 subgroup does not cause an increase in enzyme activity throughout the entire observation period, either at a daily dosage of 20 mg (NAG - 12.36±2.65 ncat/1 14.1±5.23 ncat/1 and after 3 and 6 months, LAAP - 9.4±1.62 and 11.2±2.99 ncat/1 after 3 and 6 months), or at a dosage of 40 mg/day (NAG - 30.47±3.85 and 26.2±6.75 ncat/1 after 3 and 6 months; LAAP -17.3±3.56 and 19.58±3.83 ncat/1 after 3 and 6 months). Taking simvastatin 20 mg/day in patients with CHF with DM 2 causes an increase in the NAG activity: 26.68±6.03 and 34.57±9.73 ncat/1 after 3 and 6 months). Taking simvastatin 40 mg/day increase both enzyme activity: NAG -34.3±8.7 and 46.94±9.02 ncat/1 after 3 and 6 months, LAAP - 17.08±5.81 and 22.41±4.89 ncat/1 after 3 and 6 months).Conclusion. The appointment of simvastatin in patients with dyslipidemia on the background of obesity is permissible in order to normalize lipid metabolism. Safe for the functional state of the proximal renal tubules, long-term administration of simvastatin, within the limits of medium-therapeutic dosages, is possible for patients without type 2 diabetes. Long-term use of simvastatin in patients with dyslipidemia on the background of type 2 diabetes mellitus has a negative effect on the epithelium of the proximal renal tubules, in the form of an increase in the activity of renal organ-specific enzymes, which indicates an increased dystrophy of the epithelium.

Polydatin-loaded chitosan nanoparticles ameliorates early diabetic nephropathy by attenuating oxidative stress and inflammatory responses in streptozotocin-induced diabetic rat.

In various developed countries, diabetic nephropathy (DN) is the principal cause of end-stage kidney disease and a main reason of injury and mortality in individuals with renal morbidity worldwide. Polydatin (POL) has been evaluated as a potential antioxidant, anti-inflammatory and a nephroprotective agent. In spite of this, the possible benefits and protective effects of POL on early diabetic nephropathy are not quite clarified. For the effective clearance from the body besides safe drug delivery, biodegradable nanoparticles have interesting attraction. This work was designed to evaluate the positive effect and possible mechanisms of Polydatin-loaded Chitosan-Nanoparticles (POL-NPs) on early DN in streptozotocin-induced diabetic rats. Followed the induction of diabetes, rats classified into four groups, diabetic control and diabetic rats treated daily and orally with; POL, Polydatin-loaded chitosan-Nanoparticles (POL-NPs), plus normal control rats. Our findings showed that diabetic group presented a significant high level of the blood glucose, blood glycosylated hemoglobin (HbA1c), serum insulin, renal function related parameters, renal Advanced glycation-end products (AGEs) and lipid peroxidation level compared to normal control rats, while serum albumin level and the activities of renal antioxidant enzymes were significantly decreased. Moreover, in the kidney of diabetic rat mRNA expression of nuclear factor-kappa B (NF-κB) and cyclooxygenase-2 (Cox-2) were up-regulated. Besides, increase in serum levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-18) and decrease in anti-inflammatory cytokine (IL-10). POL and POL-NPs supplementation were significantly attenuate the above-mention results and returned the normal equilibrium between pro- and anti-inflammatory cytokines. In conclusion, POL and POL-NPs have antidiabetic effect, suppresses oxidative stress and mitigates renal inflammation through inhibition of NF-κB in diabetic kidney in early progressive DN.

Basil (Ocimum basilicum L.) and/or Celery (Apium graveolens L.) Leaves Aqueous Extracts Role in Opposition to Drinking Contaminated Water Induced Male Rats Urinary Stones and Renal Deteriorations

Aims: The current research was designed to explore the role of basil and/or celery leaves aqueous extracts against urinary stones (urolithiasis) and renal deteriorations induced by drinking water contaminated with ethylene glycol (EG) and ammonium chloride (AC) in male rats.&#x0D; Place and Duration of Study: The Medical Research Center of the Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt. The experiment duration was 35 days, 7 days for acclimatization followed by 28 days experimentation.&#x0D; Methodology: Fifty-five adult male Sprague-Dawley rats were classified randomly into 5 groups of ten animals each, except urolithiatic control group which contained 15 rats. Rats were treated as follow: Group I: healthy control group (HCG), rats drank distilled water and received a placebo 1 ml distilled water daily by intra-gastric tube ; Group II: urolithiatic control group (UCG), rats drank distilled water containing ( 0.75% EG and 1% AC ) and the access to water was ad libitum and received 1 ml distilled water daily by intra-gastric tube.; Group III : urolithiatic rats supplemented with aqueous basil extract(U+ABE), rats drank distilled water containing ( 0.75% EG and 1% AC) and the access to water was ad libitum and supplemented with (200mg/kg body weight) aqueous basil extract daily by intra-gastric tube.; Group IV: urolithiatic rats supplemented with aqueous celery extract(U+ACE), rats drank distilled water containing ( 0.75% EG and 1% AC) and the access to water was ad libitum and supplemented with (200mg/kg body weight) aqueous celery extract daily by intra-gastric tube. ; Group V: urolithiatic rats supplemented with aqueous basil and celery extract(U+ABE+ACE) , rats drank distilled water containing ( 0.75% EG and 1% AC) and the access to water was ad libitum and supplemented with (100mg/kg body weight) aqueous basil extract and (100mg/kg body weight) aqueous celery extract daily by intra-gastric tube. At the end of the study 28 days, 24 h urine samples were collected from each individual animal and then rats were sacrificed under sodium barbiturate anesthesia. Blood samples were collected from the hepatic portal vein, serum was separated for biochemical analyses. Kidney samples were separated for tissue homogenate preparation, urinary bladder and ureters were separated and opened to collect urinary calculi.&#x0D; Results: Research results documented that basil and celery aqueous extracts contain significant amount of active constituents including flavonoids and polyphenols. Drinking water contaminated with EG and AC caused significant decrease (p≤0.01) in urine volume, pH, urinary and renal magnesium levels with significant increase (p≤0.01) in urinary and renal calcium, phosphate and oxalate levels. It also caused significant increase in kidney function tests [serum creatinine, uric acid, urea, as well as cystatin C] levels .Also renal enzyme activities of [acidic phosphatase (ACP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP)] activities were significantly increased (p≤0.01) with significant decrease in renal lactate dehydrogenase (LDH) activity. Water contamination also induced renal mitochondrial dysfunction (decreased complex-1 activity), apoptosis (increased caspase-3 activity) in association with a state of renal oxidative stress [increased renal malondialdehyde (MDA) level related to decreased renal reduced glutathione (GSH)level and superoxide dismutase (SOD) activity].Inflammation [increased renal tumor necrosis factor- alpha (TNF- α) and interleukin 18 (IL-18)] with suppressed immune function [decreased serum immunoglobulin (IgG and IgM)] levels were observed in urolithiatic control group. As a result of biochemical changes resulted from EG and AM administration mineral precipitation and urinary stones formation was observed in urolithiatic control group. Oral administration of aqueous basil and /or celery extracts to urolithiatic rats improved urine analysis parameters, renal functions, renal enzymes activities and mitochondrial function. Aqueous extracts also counteracted renal oxidative stress, inflammation, suppressed immune response and urinary stones formation.&#x0D; Conclusion: Research results proved that aqueous basil and/or celery extracts counteracted and ameliorated urinary stones formation and renal deteriorations associated with drinking water contaminated with EG and AC due to their content of active constituents including flavonoids and polyphenols. The most significant improvements were recorded in the group supplemented with both extracts.

Protective effects of Vitex pseudo-negundo leaves on diabetic-induced nephropathy in rats.

Objectives The belief of therapeutic effects of herbal remedies in diseases such as diabetes is rooted in medical history. The present study evaluated protective efficacy of the hydroalcoholic extract of Vitex pseudo-negundo leaves (VLHE) on the renal disorders in streptozotocin-induced diabetic rats. Methods Fifty Wistar male rats were recruited and divided into five groups of 10, including healthy controls and diabetic controls: three diabetic groups of which first group was treated with glibenclamide, and two groups treated with 250 and 500mg/kg of VLHE, respectively, for six weeks. Renal biochemical tests and tissue histopathological evaluation were performed and the antioxidant status was examined. Results There were significant decreases in superoxide dismutase and glutathione peroxidase activities and increases in malondialdehyde levels in renal tissue of diabetic groups compared with healthy controls. In the VLHE-treated rats, fasting blood sugar, blood urea nitrogen and creatinine were declined, serum albumin elevated, kidney weight lowered, lipid peroxidation and reinforcement of the activities of antioxidant enzymes decreased compared with healthy groups. Histological assessments revealed that the vacuolar degeneration of tubules and shrinkage of glomeruli in VLHE-treated rats was decreased compared with diabetic rats. Conclusions The study suggested that administrating of VLHE in nephropathic rats ameliorated the disease by reduction of oxidative stress and increase in renal antioxidant enzyme activities.

Chlorogenic acid prevents vancomycin-induced nephrotoxicity without compromising vancomycin antibacterial properties.

Vancomycin (VCM) is an effective chemotherapeutic agent commonly used against gram-positive microorganisms but has serious nephrotoxic side effects that limit its effectiveness. New therapeutics and strategies are urgently needed to combat VCM associated nephrotoxicity. In this study, we determined the protective effect of chlorogenic acid (CA) in a rat model of VCM-induced nephrotoxicity. VCM administration led to markedly elevated blood urea nitrogen and serum creatinine levels that could be prevented with CA co-administration. VCM-mediated oxidative stress was also significantly attenuated by CA as reflected by decreased malondialdehyde and nitric oxide in VCM-treated kidneys. CA administration also prevented the VCM-mediated decrease in the renal antioxidative enzyme activities of glutathione reductase, glutathione peroxidase, and catalase and led to increased levels of reduced glutathione that had been depleted by VCM. Moreover, CA administration clearly inhibited VCM-induced expression of nuclear factor-kappa B, inducible nitric oxide synthase and the downstream pro-inflammatory mediators tumor necrosis factor-α and interleukins 1β and 6. Apoptotic markers were also markedly down-regulated with CA. Overall, CA treatment mitigated VCM-induced oxidative and nitrosative stresses and countered the apoptotic and inflammatory effects of VCM. Notably, CA did not affect the antibacterial activity of VCM in vitro.

Renal changes and apoptosis caused by subacute exposure to Aroclor 1254 in selenium-deficient and selenium-supplemented rats.

Aroclor 1254 (A1254), a mixture of polychlorinated biphenyls, exerts hepatic, renal, and reproductive toxicity in rodents. This study aimed to determine a protective role of selenium on histopathological changes, oxidative stress, and apoptosis caused by A1254 in rat kidney. It included a control group, which received regular diet containing 0.15 mg/kg Se (C), a Se-supplemented group (SeS) receiving 1 mg/kg Se, a Se-deficient group (SeD) receiving Se-deficient diet of ≤0.05 mg/kg Se, an A1254-treated group (A) receiving 10 mg/kg of Aroclor 1254 and regular diet, an A1254-treated group receiving Se-supplementation (ASeS), and an A1254-treated group receiving Se-deficient diet (ASeD). Treatments lasted 15 days. After 24 h of the last dose of A1254, the animals were decapitated under anaesthesia and their renal antioxidant enzyme activities, lipid peroxidation (LP), glutathione, protein oxidation, and total antioxidant capacity levels measured. Histopathological changes were evaluated by light and electron microscopy. Apoptosis was detected with the TUNEL assay. Kidney weights, CAT activities, and GSH levels decreased significantly in all A1254-treated groups. Renal atrophic changes and higher apoptotic cell counts were observed in the A and ASeD groups. Both groups also showed a significant drop in GPx1 activities (A – 34.92 % and ASeD – 86.46 %) and rise in LP (A – 30.45 % and ASeD – 20.44 %) vs control. In contrast, LP levels and apoptotic cell counts were significantly lower in the ASeS group vs the A group. Histopathological changes and renal apoptosis were particularly visible in the ASeD group. Our findings suggest that selenium supplementation provides partial protection against renal toxicity of Aroclor 1254.

Effect of moonseed vine (Triclisia gilletii Staner) on ethane-1,2-diol-induced urolithiasis and its renotoxicity in Wistar albino rats

BackgroundMoonseed vine (Triclisia gilletii Staner) in the family Menispermaceae is a robust creeper of up to 10 cm diameter, of the lowland dense rain forest. In Ondo State, located in the South Western part of Nigeria, the plant which is usually called Peshe is used for the management of renal-related ailments. The present study was undertaken to explore the efficacy of Triclisia gilletii, a folkloric therapy in the management of renal-related ailment.ResultsPhenols, steroids, saponins, and flavonoids are present in the TGME with a total antioxidant capacity of (30.36 ± 1.90 (mg GAE/g extract), LD50 greater than 5000 mg/kg b.w., and in vitro anti-nucleation activity (iC50 = 7.09 mg/mL). Calcium oxalate stone formation as a result of oxalate from ethane-1,2-diol was evident by hypocalcemia, and further electrolyte imbalance and decreased glomerular filtration rate. The enhanced oxidative milieu in hyperoxaluria was evident by increased MDA and PC and decreased enzymatic and non-enzymatic antioxidants as well as renal membrane enzymes activities. The renal histopathological study further emphasized oxalate-induced damage and the ameliorative potential of TGME.ConclusionThe abnormal biochemical, redox electrolyte, membrane integrity, and histological alterations were attenuated by TGME which affirms its usage as nephroprotectant.

"Bottom-Up" Strategy for the Identification of Novel Soybean Peptides with Angiotensin-Converting Enzyme Inhibitory Activity.

IAVPTGVA (Soy1) and LPYP are two soybean peptides, which display a multifunctional behavior, showing in vitro hypocholesterolemic and hypoglycemic activities. A preliminary screening of their structures using BIOPEP suggested that they might be potential angiotensin-converting enzyme (ACE) inhibitors. Therefore, a bottom-up-aided approach was developed in order to clarify the in vitro hypotensive activity. Soy1 and LPYP dropped the intestinal and renal ACE enzyme activity with IC50 values equal to 14.7 ± 0.28 and 5.0 ± 0.28 μM (Caco-2 cells), and 6.0 ± 0.35 and 6.8 ± 0.20 μM (HK-2 cells), respectively. In parallel, a molecular modeling study suggested their capability to act as competitive inhibitors of this enzyme. Finally, in order to increase both their stability and hypotensive properties, a suitable strategy for the harmless control of their release from a nanomaterial was developed through their encapsulation into the RADA16-assembling peptide.