Histological Changes In Kidney Tissues Research Articles

Potential of Bauhinia variegata leaves in the management of diabetic nephropathy

The present study was carried out to explore the potential of aqueous extract of leaves of Bauhinia variegata (AE) in the treatment of streptozotocin-induced diabetic nephropathy in rats. Diabetes was induced in male Sprague Dawley rats with streptozotocin (STZ) at a dose of 55 mg/kg (i.p.). Four weeks after induction of diabetes animals were treated with the extract at a dose of 250, 500 and 1000 mg/kg for 28 days. On the 28th day, biochemical parameters (glucose, glycosylated haemoglobin, total protein, albumin, creatinine, blood urea nitrogen) and urine parameters (total protein, creatinine) were evaluated. After completion of 28 days of treatment, animals were sacrificed and kidneys were isolated. Histopathological evaluation of kidney tissue was carried out by staining the tissue sections with hematoxylin and eosin (HE) stain, Periodic acid–Schiff (PAS) stain and Trichrome stain. Treatment with AE to diabetic rats for 28 days showed a significant decrease in fasting blood glucose, glycosylated haemoglobin, and biochemical parameter like albumin, total protein, creatinine, and blood urea nitrogen (BUN) which is an important marker for the progression of diabetic nephropathy. AE treatment also improved the urine parameters and histological changes in kidney tissue of STZ induced diabetic rats after 28 days of treatment. In-vitro advanced glycation end product inhibitory assay showed that AE possesses AGE inhibitory activity which can play important role in the prevention of DN progression. Present studies proved the potential of aqueous extract of Bauhinia variegata leaves and open a new alternative treatment approach for diabetic nephropathy.

Hedysarum polybotrys polysaccharide attenuates renal inflammatory infiltration and fibrosis in diabetic mice by inhibiting the HMGB1/RAGE/TLR4 pathway.

Diabetic kidney disease (DKD) is a leading cause of kidney failure. Previous studies demonstrated the therapeutic potential of Astragalus polysaccharide in treating diabetic nephropathy. Astragalus and Hongqi both come from the leguminous plant Astragalus, but their species and genera are different, belonging to the same family and different genera of traditional Chinese medicinal plants. However, the effects of Hedysarum polybotrys polysaccharide (HPS), a polysaccharide compound from Hongqi, on DKD, including its components and efficacy, have remained elusive. The present study utilized db/db mice as a DKD animal model administered with low (30 mg/kg) and high doses (60 mg/kg) of HPS, in addition to glyburide (7.2 mg/kg). Blood and urine samples were collected from mice and blood glucose, serum creatinine, urinary albumin excretion and urinary β2-microglobulin were measured. In addition, apoptosis and histological changes in kidney tissue were observed using TUNEL and HE staining, respectively, and the secretion and expression of inflammatory factors in kidney tissue were detected using EILSA and reverse transcription-quantitative PCR. Furthermore, we the expression of fibrosis-related proteins and NF-κB signaling pathway proteins was determined using western blot analysis. HPS was found to reduce the blood glucose concentration, serum creatinine levels, urinary albumin excretion rates and urinary β2-microglobulin in a dose-dependent manner. In addition, HPS treatment mitigated apoptosis and pathological damage in the kidney tissues of DKD mice. The expression levels of fibrosis-related proteins fibronectin, α-smooth muscle actin and TGF-β1 were observed to be decreased in kidney tissues of DKD mice following HPS treatment. The secretion levels of inflammatory factors (IL-6, TNF-α and IL-1β) were also reduced in kidney tissues, with high-dose HPS treatment found to be more effective, similar to the effects mediated by the glyburide. Further mechanistic analysis revealed that the therapeutic effects of HPS on DKD mice may be mediated by inhibiting the high mobility group box 1/receptor for advanced glycation end-products/toll-like receptor 4 pathway. In conclusion, the present findings could provide insight for the treatment of DKD.

Effects of Apocynin against Monosodium Glutamate-Induced Oxidative Damage in Rat Kidne

Objective: Monosodium glutamate causes oxidative stress that affects a variety of organ systems, along with the kidney. The aim of this study was to evaluate the protective role of apocynin in kidney degeneration caused by monosodium glutamate using biochemical and histological methods. Materials and Methods: Sprague-Dawley rats (n=32) were used for this study. Four experimental groups were randomly formed: the Control (Cont), Apocynin (APO), Monosodium Glutamate (MSG), and MSG+APO groups. The MSG group received oral administration of MSG (120 mg/kg) for 28 days. The MSG+APO and APO groups received apocynin (25 mg/kg) during the last 5 days of the experiment. Kidney tissue was processed for biochemical and microscopic analyses. Biochemical methods were used to examine the levels of malondialdehyde (MDA) and glutathione (GSH) in the tissue and the activities of myeloperoxidase (MPO) and superoxide dismutase (SOD). Light and electron microscopy were also used to examine for histological changes in kidney tissue. Results: The MSG group was compared with the Cont and APO groups; it was found that MDA and MPO levels were elevated, whereas GSH and SOD activity were decreased. In contrast to the Cont and APO groups, the MSG+APO group showed higher GSH levels, lower MPO activities and increased MDA levels. While apocynin treatment improved renal tissue histology, MSGinduction led to deterioration of renal morphology. Conclusion: The study revealed that MSG increased oxidative damage and renal tissue degeneration. Moreover, apocynin reduced renal damage by modulating the ratio of antioxidants to oxidants.

Histological changes in female mice kidneys as a result of Valproic acid drug treatment

Valproic acid is a broad spectrum anti- convulsant drug, established as a long – term treatment for epilepsy and has toxic effect on kidney tissues. This study aimed to investigate the histological changes that may occur in the kidney in association with prolonged administration and overdose treatment of valproic acid. 35 albino mice were used, they were divided into four groups, group(I) included 5 animals and served as control group, group(II) included 10 animals and given progressive doses of valproic acid for ten weeks, starting with (15mg/kg/day) as minimum recommended dose and ending with (60mg/kg/day) as maximum recommended dose, group(III) included 10 animals and received an overdose (120mg/kg/day) for one week, group(IV) included 10 animals and treated exactly as group(II) then the animals were left for recovery for three weeks. The animals were sacrificed at the end of each period and the kidney tissue was excised. The drug induced many histological changes in kidney tissues, including inflammatory cellular infiltration, cell necrosis, cloudy swelling, hydropic degeneration, hemorrhage areas, oedema, and collagen deposition. The study concluded that valproic acid has multiple toxic effects on kidney tissues as far as the histological studies concerned and the effects were dependent on the dose and on the duration of treatment. Incomplete recovery was recorded after discontinuation of the drug.

Neointimal hyperplasia in the inferior vena cava of adenine-induced chronic kidney disease rats with aortocaval fistulas

The failure of autologous arteriovenous fistulas (AVFs) occurs primarily due to stenosis in the anastomotic site, which is mainly related to the development of neointimal hyperplasia (NIH). Therefore, we conducted a study to establish a novel approach to create aortocaval fistulas (ACFs) in adenine-induced (AD) chronic kidney disease (CKD) rats to study the NIH in the inferior vena cava. Ten adult female rats received a 0.75% adenine-rich diet for 4weeks to induce CKD and underwent ACF surgery. Ten healthy rats served as controls. A 5-10-mm segment of a vein immediately adjacent to that the portion of the vein used for creating the fistula was surgically removed at the time of creating the fistula, and reconstruction of the failed fistula from the same patient was used as controls. ACF was assessed using duplex scans and histopathological analyses. At the end of the experiment, AD rats showed higher serum creatinine and urea nitrogen than those of vehicle-treated rats. Remarkable histological changes in kidney tissues demonstrated successful CKD models. Sections of the ACF in AD rats and veins removed at the time of the reconstruction of the failed fistula of the patient demonstrated that the eccentric neointima formation is irregularly thickened, with several small vessels within a more cellular region of the neointima. Immunohistochemistry demonstrated the presence of myofibroblasts, contractile smooth muscle cells and macrophages within the neointima. Our rat models with ACFs showed typical features of NIH in the formation of fistula stenosis, which can resemble clinical findings in uremic patients.

MiR-22-3p suppresses sepsis-induced acute kidney injury by targeting PTEN.

Background: Septic acute kidney injury is considered as a severe and frequent complication that occurs during sepsis. The present study was performed to understand the role of miR-22-3p and its underlying mechanism in sepsis-induced acute kidney injury.Methods: Rats were injected with adenovirus carrying miR-22-3p or miR-NC in the caudal vein before cecal ligation. Meanwhile, HK-2 cells were transfected with the above adenovirus following LPS stimulation. We measured the markers of renal injury (blood urea nitrogen (BUN), serum creatinine (SCR)). Histological changes in kidney tissues were examined by hematoxylin and eosin (H&E), Masson staining, periodic acid Schiff staining and TUNEL staining. The levels of IL-1β, IL-6, TNF-α and NO were determined by ELISA assay. Using TargetScan prediction and luciferase reporter assay, we predicted and validated the association between PTEN and miR-22-3p.Results: Our data showed that miR-22-3p was significantly down-regulated in a rat model of sepsis-induced acute kidney injury, in vivo and LPS-induced sepsis model in HK-2 cells, in vitro. Overexpression of miR-22-3p remarkably suppressed the inflammatory response and apoptosis via down-regulating HMGB1, p-p65, TLR4 and pro-inflammatory factors (IL-1β, IL-6, TNF-α and NO), both in vivo and in vitro. Moreover, PTEN was identified as a target of miR-22-3p. Furthermore, PTEN knockdown augmented, while overexpression reversed the suppressive role of miR-22-3p in LPS-induced inflammatory response.Conclusions: Our results showed that miR-22-3p induced protective role in sepsis-induced acute kidney injury may rely on the repression of PTEN.

Hydrogen-rich water alleviates cyclosporine A-induced nephrotoxicity via the Keap1/Nrf2 signaling pathway.

Oxidativestress induced by long-term cyclosporine A (CsA) administration is a major cause of chronic nephrotoxicity, which is characterized by tubular atrophy, tubular cell apoptosis, and interstitial fibrosis in the progression of organ transplantation. Although hydrogen-rich water (HRW) has been used to prevent various oxidative stress-related diseases, its underlying mechanisms remain unclear. This study investigated the effects of HRW on CsA-induced nephrotoxicity and its potential mechanisms. After administration of CsA (25 mg/kg/day), rats were treated with or without HRW (12 mL/kg) for 4 weeks. Renal function and vascular activity were investigated. Histological changes in kidney tissues were analyzed using Masson's trichrome and terminal deoxynucleotidyl transferase dUTP nick-end labeling stains. Oxidative stress markers and the activation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway were also measured. We found that CsA increased the levels of reactive oxygen species (ROS) and malonaldehyde (MDA), but it reduced glutathione (GSH) and superoxide dismutase (SOD) levels. Such alterations induced vascular dysfunction, tubular atrophy, interstitial fibrosis, and tubular apoptosis. This was evident secondary to an increase in urinary protein, serum creatinine, and blood urea nitrogen, ultimately leading to renal dysfunction. Conversely, HRW decreased levels of ROS and MDA while increasing the activity of GSH and SOD. This was accompanied by an improvement in vascular and renal function. Moreover, HRW significantly decreased the level of Keap1 and increased the expression of Nrf2, NADPH dehydrogenase quinone 1, and heme oxygenase 1. In conclusion, HRW restored the balance of redox status, suppressed oxidative stress damage, and improved kidney function induced by CsA via activation of the Keap1/Nrf2 signaling pathway.

Chenopodium murale essential oil alleviates the genotoxicity and oxidative stress of silver nanoparticles in the rat kidney

This study aimed to synthesize AgNPs using Chenopodium murale extract (CME), to evaluate the antioxidant activity of the Chenopodium murale essential oil (CMEO) and the protective role against nephrotoxicity of AgNPs. Seven groups of female Sprague-Dawley rats were treated orally for 21 days included the control group, AgNPs-treated groups (25 or 50 mg/kg b.w), CMEO-treated groups (0.5 or 1 mg/kg b.w) and AgNPs plus CMEO-treated groups. The synthesized AgNPs were 30-50 nm in size. CMEO is rich in total phenolic and flavoniods and showed high antioxidant and radicals scavenging activity in vitro. AgNPs disturbed kidney function, decreased the antioxidant enzymes, increased serum electrolytes, TNF-α, MDA and NO, up-regulated Bcl-2, down-regulated Bax and P53 and induced histological changes in kidney tissue. CMEO protected the kidney against AgNPs toxicity in a dose-dependent manner. It could be concluded that AgNPs induced cytotoxicity and oxidative stress in the kidney. CMEO overcomes the nephrotoxicity and should be considered as a supplement to protect the kidney against oxidative stress.

Protective effect of ethyl acetate fraction of Biophytum sensitivum extract against sodium oxalate-induced urolithiasis in rats

The methanolic whole plant extract of Biophytum sensitivum (感应草gǎnyìng cǎo) has been found to possess antiurolithiatic effect. The present study was undertaken to evaluate the antiurolithiatic effect of some fractions of methanolic whole plant extract of B. sensitivum (MBS) in rats as a step toward activity-directed isolation of antiurolithiatic component. The MBS was successively extracted with dichloromethane, ethyl acetate, ethanol and water to obtain fractions. Sodium oxalate (70 mg/kg, i.p.) was administered to rats for seven days to develop calcium oxalate urolithiasis. These rats were treated with two doses (20 and 40 mg/kg, p.o.) of the fractions, 1 h before sodium oxalate injections. Antiurolithiatic activity was assessed by estimating biochemical changes in urine, serum and kidney homogenate along with histological changes in kidney tissue. Sodium oxalate administration caused biochemical alterations in urine which was found to be prevented significantly by the ethyl acetate fraction. Supplementation with ethyl acetate fraction prevented the elevation of serum creatinine, uric acid and blood urea nitrogen levels. The elevated calcium, oxalate and phosphate levels in the kidney tissue homogenate of lithiatic rats were significantly reduced by the treatment with ethyl acetate fraction. The ethyl acetate fraction also caused significant decrease in lipid peroxidation activity, accumulation of calcium oxalate deposits and histological changes in the kidney tissue. The results showed that the antiurolithiatic component of the methanolic whole plant extract of the plant is contained in the ethyl acetate fraction. The effect is attributed to its diuretic, antioxidant, nephroprotective properties and effect on lowering the concentration of urinary stone-forming constituents.