Histopathological Changes In Renal Tissues Research Articles

Time-Dependent Molecular Changes Following MDMA-Induced Nephrotoxicity

: The increasing recreational use of ecstasy (MDMA) poses significant risks to human health, including reports of fatal renal failure due to its adverse renal effects. While MDMA-induced renal toxicity might result from systemic effects, there is also substantial evidence of direct harm to renal tissues by MDMA or its metabolites. The precise mechanisms underlying renal toxicity remain unclear. This study explored the impact of a single intraperitoneal dose of MDMA (20 mg/kg) on rat kidneys. Serum BUN and creatinine levels were evaluated to assess renal function, while TNF-α and TGF-β protein concentrations were measured using ELISA. mRNA levels of Bax, Bcl-xl, and Bcl-2 were quantified using quantitative RT-PCR. Additionally, apoptosis and histopathological changes in renal tissue were examined. Results showed a transient increase in serum BUN and creatinine in MDMA-treated rats. There were decreases in TNF-α and TGF-β levels in the renal tissue. Both pro-apoptotic Bax and anti-apoptotic Bcl-xl gene expressions were significantly reduced, whereas Bcl-2 expression and apoptosis did not show significant changes. No structural alterations were observed in the renal tissues. Overall, this study suggests that the renal adverse effects of MDMA may be mediated through the disruption of cytokine pathways, with notable reductions in TGF-β possibly linked to decreased TNF-α levels.

Luteolin attenuates diabetic nephropathy via inhibition of metalloenzymes in rats

Objective: To investigate the renoprotective effects of luteolin on diabetes in rats. Methods: One week after administration of streptozotocin 55 mg/kg intraperitoneally, rats were given 25, 50, and 75 mg/kg/day of luteolin orally for another eight weeks. At the end of the experiment, body weight, blood glucose level, biochemical parameters for renal function (serum creatinine, blood urea nitrogen, uric acid, serum albumin, and total protein), kidney histology, matrix metalloproteinase (MMP)-2, MMP-9, and histone deacetylase 2 (HDAC-2) expression, and malondialdehyde, myeloperoxidase, and hydroxyproline content in renal tissue were evaluated. High glucose- induced damage using NRK-52E cell line was studied to evaluate cell viability and metalloenzyme expression. Additionally, in silico studies including docking and molecular dynamics simulations were conducted. Results: MMP-2, MMP-9, and HDAC-2 expressions were significantly increased in high glucose-induced NRK-52E cells and the renal tissue of diabetic rats. However, these changes were reversed by luteolin at the administered doses. Additionally, luteolin significantly reduced oxidative stress, inflammation, and fibrosis, as well as improved biochemical parameters in diabetic rats. Furthermore, luteolin at the examined doses markedly alleviated diabetes-induced histopathological changes in renal tissues. Conclusions: Luteolin effectively attenuates streptozotocin- induced diabetic nephropathy in rats by inhibiting MMP-2, MMP- 9, and HDAC-2 expression, and reducing oxidative stress and inflammation.

BaoShenTongLuo formula protects against podocyte injury by regulating AMPK-mediated mitochondrial biogenesis in diabetic kidney disease

BackgroundMitochondrial dysfunction is considered to be an important contributor in podocyte injury under diabetic conditions. The BaoShenTongLuo (BSTL) formula has been shown to reduce podocyte damage and postpone the progression of diabetic kidney disease (DKD). The potential mechanisms underlying the effects of BSTL, however, have yet to be elucidated. In this study, we aimed to investigate whether the effects of BSTL are related to the regulation of mitochondrial biogenesis via the adenosine monophosphate-activated protein kinase (AMPK) pathway.MethodsHigh-Performance Liquid Chromatography Electrospray Ionization Mass Spectrometer (HPLC–ESI–MS) analysis was performed to investigate the characteristics of pure compounds in BSTL. db/db mice and mouse podocyte clone-5 (MPC5) cells were exposed to high glucose (HG) to induce DKD and podocyte damage. Body weight, random blood glucose, urinary albumin/creatinine ratio (UACR), indicators of renal function and renal histological lesions were measured. Markers of podocyte injury, mitochondrial morphology, mitochondrial deoxyribonucleic acid (mtDNA) content, mitochondrial respiratory chain complexes activities, reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) levels were assessed. Protein expressions of AMPK, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), transcription factor A (TFAM), mitochondrial fusion protein 2 (MFN2) and dynamin-related protein 1 (DRP1) were also detected. MPC5 cells were transfected with AMPKα small interfering RNA (AMPKα siRNA) to determine the underlying mechanisms of BSTL improvement of mitochondrial function under diabetic conditions.ResultsIn vivo, treatment with BSTL reduced the UACR levels, reversed the histopathological changes in renal tissues, and alleviated the podocyte injury observed in db/db mice. After BSTL treatment, the decreased mtDNA content and mitochondrial respiratory chain complex I, III, and IV activities were significantly improved, and these effects were accompanied by maintenance of the protein expression of p-AMPKαT172, PGC-1α, TFAM and MFN2. The in vitro experiments also showed that BSTL reduced podocyte apoptosis, suppressed excessive cellular ROS production, and reversed the decreased in MMP that were observed under HG conditions. More importantly, the effects of BSTL in enhancing mitochondrial biogenesis and reducing podocyte apoptosis were inhibited in AMPKα siRNA-treated podocytes.ConclusionBSTL plays a crucial role in protecting against podocyte injury by regulating the AMPK-mediated mitochondrial biogenesis in DKD.

Raspberry Ketone Protects Kidney Damage in Diabetic Nephropathy by Improving Kidney Mitochondrial Dysfunction

Mitochondrial dysfunction and oxidative stress play essential roles in the pathogenesis of diabetic nephropathy (DN). The respiratory oxygen consumption and oxidative stress status of kidney mitochondria are closely associated with the development of DN. In this study, raspberry ketone (RK), the predominant bioactive component extracted from raspberry, was applied to treat the established DN mice model. This study investigated whether RK protects the kidneys of high-fat and high-sugar/streptozotocin (STZ)-induced diabetic rats by inhibiting oxidative stress and ameliorating mitochondrial dysfunction. Besides, the DN mice models were established by injecting high-fat and high-sugar/STZ (130 mg/kg, intraperitoneal injection). The animals were randomly divided into the control group (normal saline, ig), DN group (normal saline, ig), DN + RK group (200 mg/kg RK + normal saline, ig), DN + RK group (400 mg/kg RK + normal saline, ig), and DN + Metformin (Met) (200 mg/kg Met + normal saline, ig). Regular monitoring of fasting blood glucose (FBG) levels was observed in mice. After 10 weeks of drug treatment, the kidneys of mice in each group were analyzed using ultrasound, and the mice were euthanized humanely. Kidney weight (KW)/body weight (BW) and kidney injury, mitochondrial function, and oxidative stress indicators were determined. The histopathological changes in renal tissue were observed after hematoxylin and eosin (H&E) staining. The results recommended that RK has a renoprotective function on DN mice by improving mitochondrial dysfunction and inhibiting oxidative stress.

Comparative studies on protective efficacy of gentisic acid and 2-pyrocatechuic acid against 5-fluorouracil induced nephrotoxicity in Wistar rats

Nephrotoxicity is a frequent and severe side effect of 5-fluorouracil (5-FU) chemotherapy which limits its use clinically regardless of being one of the most promising chemotherapeutic agents. Here, we assessed the nephroprotective activity of two structurally related phenolic acids 2-pyrocatechuic acid (2,3 dihyroxybenzoic acid) and gentisic acid (2,5 dihyroxybenzoic acid) against 5-FU induced nephrotoxicity in Wistar rats. Intraperitoneal administration of 5-FU at a dose of 20 mg/kg once a day for 5 days produced a significant elevation in serum parameters of the kidney such as uric acid, urea, creatinine, sodium and potassium levels along with severe histopathological changes in renal tissues of rats indicating severe nephrotoxicity. Administration of 2-pyrocatechuic acid (2-PCA) at 10, 30 and 100 by oral route for 9 days and additional 5 days with 5-FU resulted in an amelioration of altered serum parameters in a dose-dependent manner. Moreover, 2-PCA attenuated the renal damage produced by 5-FU demonstrating its efficacy as a nephroprotective agent for the prevention as well as amelioration of 5-FU induced nephrotoxicity. None of the doses of gentisic acid (GA) were found to be effective in this posology when given orally.

Protective Effect of Keluoxin against Diabetic Nephropathy in Type 2 Diabetic Mellitus Models.

Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus (DM). Renal dysfunction and persistent proteinuria are the main clinical features of DN. Podocyte injury is an important cause of persistent proteinuria and diabetic kidney disease (DKD) progression. Traditional Chinese patent medicines can improve renal function by enhancing autophagy and promoting apoptosis. Keluoxin is a Chinese patent medicine that has the effect of invigorating qi and nourishing yin, activating blood, and eliminating blood stasis. Therefore, we hypothesized that Keluoxin may have a protective effect against diabetic nephropathy in rats with type 2 DM. Rats induced with diabetes through streptozocin (STZ) injection and a high-fat and high-sugar diet were treated with Keluoxin (0.63 g/kg/day) for 8 weeks, and renal function, biochemical indicators, and histopathological changes in renal tissues were observed. Immunofluorescence staining and western blot analysis were used to detect the expression of autophagy-related proteins. The results showed that Keluoxin reduced blood glucose and lipid levels, improved renal function, and alleviated renal histopathological changes in rats with DN. The therapeutic effect was similar to that of Irbesartan (15.6 mg/kg/day). It is inferred that the mechanism works through reducing the obstruction of downstream pathways of autophagy by improving the lysosomal degradation function and alleviating podocyte injury. This study demonstrates that Keluoxin could regulate autophagy in podocytes, alleviate kidney injury in rats with DN, and have a protective effect on renal function; its mechanism can thus be a potential therapy for DN.

Juglanin protects against high fat diet-induced renal injury by suppressing inflammation and dyslipidemia via regulating NF-κB/HDAC3 signaling

Obesity is an important factor implicated in chronic kidney disease (CKD). Juglanin (Jug) is a natural compound extracted from the crude Polygonumaviculare, showing anti-inflammatory and anti-diabetic effects. However, whether Jug has protective effects against obesity-induced renal injury, little has been investigated. Herein, we attempted to explore the potential of Jug in mediating obesity-induced kidney disease in high fat diet (HFD)-challenged mice. Our results suggested that chronic HFD feeding markedly increased the body weights of mice compared to the ones fed with normal chow diet (NCD), along with significant glucose intolerance and insulin resistance. However, these metabolic disorders induced by HFD were effectively alleviated by Jug treatments in a dose-dependent manner. Moreover, HFD-challenged mice showed apparent histopathological changes in renal tissues with significant collagen accumulation, which were attenuated by Jug supplementation. In addition, Jug treatment decreased the expression levels of kidney injury molecule-1 (KIM-1), while increased nephrin and podocin expression levels in kidney of HFD-challenged mice, improving the renal dysfunction. Furthermore, HFD led to lipid deposition in kidney samples of mice by enhancing abnormal lipid metabolism. In addition, HFD promoted the releases of circulating pro-inflammatory cytokines, and enhanced the renal inflammation by activating nuclear factor-kappa B/histone deacetylase 3 (NF-κB/HDAC3) signaling. HFD-induced dyslipidemia and inflammation were considerably abrogated by Jug administration in mice. The protective effects of Jug against renal injury were confirmed in palmitate (PA)-stimulated HK2 cells in vitro mainly through suppressing the nuclear translocation of NF-κB and HDAC3, repressing inflammation and lipid accumulation eventually. Hence, Jug could ameliorate HFD-induced kidney injury mainly through blocking the NF-κB/HDAC3 nuclear translocation.

Effects of Pistacia atlantica Subsp. Kurdica on Cadmium-Induced Oxidative Damage in Rat Kidney

Background: Pistacia atlantica kurdica has recently been shown to possess free radical scavenging ability. The current study aims to investigate the protective effect of this plant against cadmium-induced nephrotoxicity. Methods: Thirty-six rats were divided into 6 groups (6 in each), and treated as follows: group 1 received normal saline (control group), group 2 (positive control) received cadmium by drinking water (100 mg/ L/d), group 3 received 200 mg/kg of P. atlantica extract, and groups 4-6 received cadmium as well as 50, 100 and 200 mg/kg/d of P. atlantica extract (orally), respectively. After 2 weeks, oxidative damage and renal function markers were assayed by standard methods. Results: In cadmium group, a significant increase was observed in serum blood urea nitrogen (BUN) (P<0.01) and lipid peroxidation (LPO) level of renal tissue (P<0.001) and a remarkable decrease was found in total thiol molecules (TTM) of the kidney (P<0.001). Despite the decreased renal antioxidant capacity, these changes were not significant. P. atlantica extract improved the LPO, TTM, and histopathological changes in renal tissue. Conclusion: In this study, although the P. atlantica extract did not have a significant effect on cadmiuminduced renal dysfunction, it did improve the oxidative/antioxidant balance in renal tissue.

The Diagnostic Value of the Changes in the Renal Glomerulus in the Postmortem Diagnosis of Freshwater Drownings.

Drowning is one of the major causes of unintentional injury death worldwide. As there are no pathomorphological findings specific to the diagnosis of drowning, definitive postmortem diagnosis of drowning continues to be a significant problem in forensic medicine. This study aims to present an additional diagnostic sign in cases of freshwater drowning by investigating the histopathological changes of renal tissue in the postmortem diagnosis of freshwater drowning. For this purpose, 103 cases were investigated in which the causes of death were freshwater drowning (n = 45), traffic accidents (n = 33) and acute myocardial infarction (n = 25). Renal corpuscular structures of selected cases were examined stereologically and histopathologically. Renal corpuscle diameter, renal corpuscle surface area, glomerular tuft surface area, and Bowman space were calculated by stereological method. When compared with the glomeruli of the control group, renal corpuscle diameter, renal corpuscle surface area, glomerular tuft surface area, and Bowman space values of kidney tissues of all freshwater drowning cases were found to be decreased (P < 0.001). These changes may be considered as an essential histopathological finding in postmortem diagnosis of freshwater drowning cases.

The Renoprotective Effects of Naringenin (NGN) in Gestational Pregnancy.

IntroductionGestational diabetes mellitus (GDM) is defined as glucose intolerance that is first diagnosed during pregnancy, a condition risking the health of both the mother and the baby. Naringenin (NGN) has been demonstrated to have multiple therapeutic functions, while it is also considered to exhibit antidiabetic properties. The present study aimed to investigate the protective effects of NGN in pregnant diabetic rats.MethodsGDM was induced by feeding the rats with a high-fat diet for 5 weeks, followed by intraperitoneal injection of streptozotocin (35 mg/kg). The fasting blood glucose were determined with a glucometer and the 24-h urine protein (24-UPro) were determined by the sulfonyl salicylic acid method. The pathological morphological changes and apoptosis of glomeruli cells of kidney tissue using hematoxylin and eosin (H&E) staining and TUNEL analysis. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the serum T-AOC, the activity of SOD, the levels of GSH-Px, CAT and MDA, TNF-α, IL-6, TGF-β, ICAM-1.The expression of related genes were measured by RT-qPCR and Western blot analyses.ResultsIn the NGN-treated group, it was observed that the general status of the rats was improved, while the levels of blood glucose and 24-UPro were significantly decreased. In addition, the histopathological changes in renal tissues and renal cell apoptosis were significantly improved upon treatment with NGN. The expression levels of oxidative stress and inflammation-associated factors also differed signifigcantly between the model and NGN-treated groups. Upon treatment with NGN, the levels of peroxisome proliferator-activated receptor α were significantly increased, while the activity of enzymes involved in the oxidative metabolism of fatty acids was significantly decreased.ConclusionThese preliminary experimental findings demonstrate that NGN has a certain renoprotective effect on GDM, which provides a novel therapeutic option for this condition.

Ethyl acetate extract of Ceiba pentandra (L.) Gaertn. reduces methotrexate-induced renal damage in rats via antioxidant, anti-inflammatory, and antiapoptotic actions

Methotrexate (MTX) is a chemotherapeutic agent and an immunosuppressant used to treat cancer and autoimmune diseases. However, its use is limited by its multi-organ toxicity, including nephrotoxicity, which is related to MTX-driven oxidative stress. Silencing oxidative stressors is therefore an important strategy in minimizing MTX adverse effects.Medicinal plants rich in phenolic compounds are probable candidates to overcome these oxidants. Herein, C. pentandra ethyl acetate extract showed powerful in vitro radical-scavenging potential (IC50 = 0.0716) comparable to those of the standard natural (ascorbic acid, IC50 = 0.045) and synthetic (BHA, IC50 = 0.056) antioxidants. The effect of C. pentandra ethyl acetate extract against MTX-induced nephrotoxicity in rats was evaluated by administering the extract (400 mg/kg/day) or the standard antioxidant silymarin (100 mg/kg/day) orally for 5 days before and 5 days after a single MTX injection (20 mg/kg, i.p.).C. pentandra showed slight superiorities over silymarin in restoring the MTX-impaired renal functions, with approximately twofold decreases in overall kidney function tests. C. pentandra also improved renal antioxidant capacity and reduced the MTX-induced oxidative stress. Moreover, C. pentandra inhibited MTX-initiated apoptotic and inflammatory cascades, and attenuated MTX-induced histopathological changes in renal tissue architecture.Phytochemical investigation of the extract led to the purification of the phenolics quercitrin (1), cinchonains 1a (2) and 1b (3), cis-clovamide (4), trans-clovamide (5), and glochidioboside (6); a structurally similar with many of the reported antioxidant and nephroprotective agents. In conclusion, these data demonstrate that C. pentandra exhibits nephroprotective effect against MTX-induced kidney damage via its antioxidant, antiapoptotic and anti-inflammatory mechanisms. TaxonomyFunctional Disorder, Traditional Medicine, Herbal Medicine.

Effect of curcumin and curcumin nanoparticles against lead induced nephrotoxicity.

The aim of the present study was to examine the protective effect of curcumin (CUR) and curcumin nanoparticles (CURNPs) as antioxidants on the nephrotoxicity induced by lead (Pb). CUR (60 mg/kg b.w) and CURNPs (30 mg/kg b.w) were evaluated using Pb (30 mg/kg b.w.) induced oxidative renal damage in rats. Administration of Pb significantly (p<0.001) increased the levels of renal function test such as creatinine (CRN) and blood urea nitrogen (BUN) and uric acid (UA). Furthermore, Pb significantly decreased glutathione (GSH) levels, superoxide dismutase (SOD), glutathione reductase (GR), catalase (CAT) and glutathione peroxidase (GPx) activities (p<0.001). CUR and CURNPs displayed a renal protective effect as evident by significant decrease in CRN, BUN, UA levels and elevated the antioxidant status of renal tissues. The administration of Pb also induced histopathological changes in renal tissue; however, in groups treated by CUR and CURNPs, there was amelioration in pathological changes in renal tissue. These findings suggest that Nano CUR could be a potential compound in combating the oxidative damage of renal tissue as it increases curcumin bioavailability.

Saffron Extract Prevents Vancomycin-induced Nephrotoxicity

Background: Vancomycin, a glycopeptide antibiotic, is commonly used against methicillin-resistant Gram-positive cocci. However, the nephrotoxic side-effects of Vancomycin results in dose restriction and reduces the duration of administration. Objectives: The present study was designed to evaluate the protective effects of aqueous saffron (Crocus sativus) extract on vancomycin-induced nephrotoxicity in rats. Materials and methods: In this study 32 adult male Wistar rats were randomly divided into 4 groups of 8 rats; (i) control (ii) saffron (80 mg/kg, I.P.), (iii) vancomycin (200 mg/kg/BD, I.P.) and (iv) vancomycin plus saffron. The saffron treatment began 24 hours before the administration of the vancomycin therapy and lasted 8 days, while the duration of the vancomycin therapy was 7 days. Serum creatinine and blood urea nitrogen (BUN), renal malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity and histopathological changes of renal tissue were analyzed. Results: Administration of vancomycin caused a significant increase in serum creatinine, BUN and renal MDA levels, whereas, SOD activity was decreased, when compared to the control group. Aqueous saffron extract, on the other hand, decreased serum creatinine, BUN concentration and renal MDA levels but increased the level of renal SOD activity. Substantial histopathological alterations including destruction of kidney tubules, interstitial edema, epithelia vacuolization and epithelial desquamation, were observed with the vancomycin-only treatment group. However, the administration of saffron extract resulted in a significant reduction of damage to the kidneys. Conclusion: The present study demonstrated that oxidative stress plays an important role in vancomycin induced nephrotoxicity and saffron extract has a potent renoprotective effect against vancomycin induced lipid peroxidation and nephrotoxicity.

Ursolic acid improves diabetic nephropathy via suppression of oxidative stress and inflammation in streptozotocin-induced rats.

Inflammation plays a pivotal role in the pathogenesis of diabetic nephropathy (DN). Overexpression of inflammatory chemokine and cytokines is involved in the development of DN. Ursolic acid (UA), a common pentacyclic triterpenoid compound, has been reported to have myriad benefits and medicinal properties. However, its protective effects against renal injury in streptozotocin (STZ)-induced diabetic rats have not been firmly established. In the current report, we investigated whether UA inhibits oxidative stress and inflammation in the kidneys of STZ-induced diabetic rats. Diabetes mellitus (DM) was induced by STZ (40 mg/ kg, i.v.). Animals were randomly divided into control group (normal saline, i.g.), DN group (normal saline, i.g.), DN + UA group (35 mg/kg UA + normal saline, i.g.) and DN + telmisartan group (12 mg/kg telmisartan + normal saline, i.g.). Fasting blood glucose (FBG) levels were monitored at regular intervals. The administration of compounds started at 5th week and lasted for 8 weeks. At the beginning of 13th week, rats were humanely euthanized, KW/BW, BUN, SCr, SOD and MDA were measured. Histopathological changes in renal tissue were observed after hematoxylin-eosin (HE) staining. Furthermore, the expressions of TNF-α, MCP-1 and IL-1β in kidney were determined by immunohistochemistry and western blot. Our results showed that UA significantly lowered the levels of FBG, KW/BW, BUN, SCr and MDA in diabetic rats. Additionally, the SOD activity in UA treated group was higher than that in DN group. Furthermore, renal structural abnormalities and the elevation of TNF-α, MCP-1 and IL-1β expression level were blocked by the administration of UA. In conclusion, our data demonstrate that UA could be well used as a protective agent to counter renal dysfunction - through antioxidant and anti-inflammatory effects.

Crocin mediated amelioration of oxidative burden and inflammatory cascade suppresses diabetic nephropathy progression in diabetic rats

Diabetic Nephropathy (DN) is one of the main complications associated with diabetes mellitus. Persistently elevated blood glucose level drives histopathological changes in renal tissues that hinder normal kidney functions. In the current study, crocin; the main bioactive constituent of Crocus sativus was investigated as a reno-protective agent against DN by virtue of its numerous pharmacological activities. Diabetes was induced in male Sprague-Dawely rats through intravenous injection of streptozocin (STZ) (50 mg/kg), DN was confirmed eight weeks post diabetes induction. Daily oral crocin for eight weeks (20 mg/kg) significantly reduced blood glucose level with a significant increase in insulin level. Moreover, crocin improved impaired kidney functions as manifested in reduction of serum creatinine levels, blood urea nitrogen and proteinuria with concomitant increase in urinary creatinine clearance. Furthermore, biomarkers of cell injury and tissue necrosis like LDH activity was significantly reduced, kidney content of NOS significantly declined likewise. In addition, renal antioxidants such as SOD, GSH and serum catalase activity significantly increased with concomitant reduction of kidney MDA; biomarker of oxidative load. Kidney content of toll-like receptors 4 and IL-6 significantly declined with simultaneous suppression of nuclear factor kappa-B (NF-κB/p65) protein expression and immuno-staining in rat renal cortex. Furthermore, crocin inhibited progression of renal fibrosis as seen with reduction of renal hydroxyproline and collagen content, TGF-β immuno-staining and Masson's Trichrome positive tissue. Histopathologically, crocin pretreatment was associated with minimal renal damage with fewer fibrotic lesions. There was a concomitant restoration of renal tubules integrity with preservation of glomerular space area. In conclusion, crocin's ameliorative impact on DN may be attributed to its free radicals scavenging properties, its ability to enhance host antioxidant defense system and its ability to inhibit inflammatory and fibrotic cascades activation.

Preventive effects of hesperidin on diabetic nephropathy induced by streptozotocin via modulating TGF-β1 and oxidative DNA damage

Hesperidin (HSP) is a natural bioflavonoid with active pharmacological properties. This study was conducted to investigate the hypoglycemic and antioxidant effects of HSP on streptozotocin-induced diabetic nephropathy in rats. Serum urea, creatinine and malondialdehyde levels increased in the diabetic group, while antioxidant enzyme activities decreased compared to the control group. Moreover, transforming growth factor-beta 1 level, 8-hydroxy-2′-deoxyguanosine expression and histopathological changes in renal tissue were increased in the diabetic group. On the other hand, HSP therapy significantly regulated these values in diabetic rats. Our results indicated that HSP might be helpful to protect diabetic nephropathy.

Protective effects of Monotheca buxifolia fruit on renal toxicity induced by CCl4 in rats.

BackgroundOxidative stress is believed to be a root cause of various degenerative and fibrotic disorders. Dietary foods enrich in antioxidants can cure or curtail the progression of oxidative stress induced disorders. Fruit of Monotheca buxifolia is used locally for digestive and urinary tract disorders. We have evaluated the protective potential of the methanol extract of M. buxifolia (MBM) in rat exposed to carbon tetrachloride (CCl4) toxicity.MethodsPowder of the dried fruit of M. buxifolia was extracted twice with 95 % methanol to get the extract (MBM). Presence of polyphenolic constituents was detected by HPLC-DAD (High Performance Liquid Chromatography with Diode Array Detection) analysis. Sprague-Dawley male rats were divided in to six groups with six rats in each. Animals of Group I were kept control, while rats of Group II – Group V were treated intraperitoneally with 1 ml/kg body weight (bw) of CCl4 (30 % v/v; olive oil) 15 dosages in 30 days. Animals of Group III were orally administered silymarin (50 mg/kg bw) while Group IV and V with 200 and 400 mg/kg of MBM on next day of CCl4 treatment. Rats of Group VI were administered only with 400 mg/kg bw of MBM. Biochemical markers of the urine and serum were analyzed. Level of antioxidant enzymes, DNA damages lipid peroxides (TBARS), H2O2 and nitrite was assessed in renal tissues of rat. Histopathological changes in renal tissues of rat were also recorded.ResultsHPLC-DAD analysis of MBM indicated the existence of gallic acid, catechin, caffeic acid and rutin. MBM administration significantly alleviated the toxic effect of CCl4 in rat and decreased the elevated level of RBCs, pus and epithelial cells, specific gravity, creatinine, urobilinogen, urea and albumin while increased the pH and urinary protein. Increase in the level of urobilinogen, blood urea nitrogen (BUN), urea and total bilirubin while decrease of albumin and total protein in serum was restored by the administration of MBM to CCl4 fed rat. Administration of MBM to CCl4 exposed rats significantly increased the activity level of phase I and phase II enzymes and GSH while decreased the level of TBARS, H2O2, nitrite and DNA damages in renal tissues of rat. Furthermore, histopathological alterations induced with CCl4 in renal tissues of rat were also diminished with the administration of MBM.ConclusionRestoration of various parameters induced with toxic insult of CCl4 in rat suggests the antioxidant and repairing potential of M. buxifolia fruit in kidney disorders.

Estrogen attenuates renal IRI through PPAR-γ agonism in rats

BackgroundEstrogen is reported to be renoprotective agent in various preclinical studies, attributing to its antioxidant and anti-inflammatory potential. The aim of present study was to investigate the involvement of peroxisome proliferator-activated receptor-γ (PPAR-γ) in estrogen-mediated protection against renal ischemia reperfusion injury (IRI) in rats. Materials and methodsThe renal damage induced by IRI (40-min ischemia and 24-h reperfusion) was assessed by measuring serum creatinine, creatinine clearance, blood urea nitrogen, serum uric acid, electrolytes, and microproteinuria in rats. The myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. Hematoxylin-eosin and periodic acid schiff staining of renal tissues were done to demonstrate histopathologic changes. Estrogen (0.2, 0.5, and 1.0 mg/kg, i.p.) was administered 1 h before subjecting rats to renal IRI. Separately, bisphenol A diglycyl ether (BADGE, 30 mg/kg, i.p.), a PPAR-γ receptor antagonist, was given before estrogen administration followed by IRI in rats. ResultsThe ischemia reperfusion demonstrated renal damage in rats with significant changes in serum and urinary parameters, enhanced oxidative stress, and histopathologic changes in renal tissues. Estrogen administration demonstrated marked renoprotection that was attenuated by BADGE pretreatment in rats. ConclusionsIt is concluded that PPAR-γ agonism serves as one of the mechanisms in estrogen-mediated renoprotection.

Dipyridamole attenuates ischemia reperfusion induced acute kidney injury through adenosinergic A1 and A2A receptor agonism in rats.

Dipyridamole (DYP) is an anti-platelet agent with marked vasodilator, anti-oxidant, and anti-inflammatory activity. The present study investigated the role of adenosine receptors in DYP-mediated protection against ischemia reperfusion-induced acute kidney injury (AKI) in rats. The rats were subjected to bilateral renal ischemia for 40min followed by reperfusion for 24h. The renal damage induced by ischemia reperfusion injury (IRI) was assessed by measuring creatinine clearance, blood urea nitrogen, uric acid, plasma potassium, fractional excretion of sodium, and microproteinuria in rats. The oxidative stress in renal tissues was assessed by quantification of thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The hematoxylin-eosin staining was carried out to observe histopathological changes in renal tissues. DYP (10 and 30mg/kg, intraperitoneal, i.p.) was administered 30min before subjecting the rats to renal IRI. In separate groups, caffeine (50mg/kg, i.p.), an adenosinergic A1 and A2A receptor antagonist was administered with and without DYP treatment before subjecting the rats to renal IRI. The ischemia reperfusion-induced AKI was demonstrated by significant changes in serum as well as urinary parameters, enhanced oxidative stress, and histopathological changes in renal tissues. The administration of DYP demonstrated protection against AKI. The prior treatment with caffeine abolished DYP-mediated reno-protection suggesting role of A1 and A2A adenosine receptors in DYP-mediated reno-protection in rats. It is concluded that adenosine receptors find their definite involvement in DYP-mediated anti-oxidative and reno-protective effect against ischemia reperfusion-induced AKI.

Oral administration of oleuropein attenuates cisplatin-induced acute renal injury in mice through inhibition of ERK signaling.

Oleuropein possesses numerous health beneficial effects. We investigated the renoprotective effects of oleuropein against cisplatin (CP) induced kidney injury. Male BALB/cN mice were orally gavaged with 5, 10 and 20 mg oleuropein/kg body weight for 2 days, 48 h after intraperitoneal injection of CP (13 mg/kg). Four days after CP administration, serum creatinine and blood urea nitrogen (BUN) levels were significantly elevated, with histopathological changes in renal tissue. In addition, renal oxidative stress was evidenced by increased expression of 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), cytochrome P450 E1 (CYP2E1) and heme oxygenase-1 (HO-1). The expression of nuclear factor-kappaB (NF-κB) p65, phospho-p65, tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) in the kidneys increased upon CP treatment, suggesting renal inflammation. CP intoxication increased the expression of p53, Bax and caspase-3 and induced apoptosis in the kidneys. CP administration also resulted in enhanced phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). All these effects were dose dependently diminished by oleuropein. Oral administration of PD0325901, an MEK inhibitor, coincided with the oleuropein-mediated suppression of apoptotic, inflammatory and antioxidant markers. The results of the current study suggest that oleuropein attenuated CP-induced acute renal injury, which was mediated through the inhibition of ERK signaling.