Rat Renal Tissue Research Articles

Impact of aging on kidneys of male Wistar albino rats: the protective antiaging role of resveratrol

Because aging leads to multiple health problems associated with changes in the structure and functions of a different organ system, this study aimed to assess the effect of aging on the histology of renal tissue in rats of various ages and the possible protective role of resveratrol. In the present study, twenty-four male Wistar albino rats were separated into three groups of eight animals each, including rats adult aged (6 months), and old-aged (24 months old). The elderly resveratrol-treated group was administered 25 mg/kg/day of resveratrol diluted in distilled water orally via gastric tube. The treatment lasted three months. At the end of the experiment, blood was drawn for serum creatinine analysis, the animals were sacrificed, and the kidneys were removed and processed for histological investigation. The findings revealed variable changes in kidney tissue, including glomerulosclerosis, compensatory glomerular hypertrophy, tubulointerstitial fibrosis, thickened glomerular basement membrane, arterial sclerosis, tubular dilatation with cast formation, atrophy of the tubules, infiltration of inflammatory cells, a rise in the rate of apoptotic cells, and a decrease in the glomerular number. These histological changes were associated with increased serum creatinine levels and kidney malondialdehyde (MDA), a marker of lipid peroxidation. The use of RES (Resveratrol) improved the creatinine level with a decrease in the MDA and improved the histological changes of aged kidney. As a result, the progression of aging was accompanied by different histological variations that interfered with the physiological functioning of the kidney, predisposing older persons to renal illnesses. Utilizing RES as a prophylactic and/or therapeutic medicine for aging-related renal changes is also possible.

Endotoxin induced acute kidney injury modulates expression of AQP1, P53 and P21 in rat kidney, heart, lung and small intestine.

This study was designed to explore whether aquaporin 1(AQP1), P53 and P21 can be used as diagnostic biomarkers of lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and potential indicators of sepsis-induced multiple organ injury. Bioinformatics results demonstrated that AQP1, P53, P21 was dramatically elevated 6h after Cecal ligation and puncture (CLP)-AKI in rat renal tissue. The expression of AQP1, P53, P21, NGAL and KIM-1 in kidney were increased significantly at first and then decreased gradually in LPS-induced AKI rats. Histopathological sections showed swelling of tubular epithelial cells and destruction of basic structures as well as infiltration of numerous inflammatory cells in LPS-induced AKI. Moreover, the expressions of AQP1, P53 and P21 in heart were significantly increased in LPS treatment rats, while the AQP1 expressions in lung and small intestine were significantly decreased. The level of NGAL mRNA in heart, lung and small intestine was firstly increased and then decreased during LPS treatment rats, but the expression of KIM-1 mRNA was not affected. Therefore, our results suggest that AQP1, P53 and P21 is remarkably upregulated in LPS-induced AKI, which may be considered as a potential novel diagnostic biomarker of Septic AKI. NGAL may serve as a biomarker of sepsis-induced multiple organ damage during the process of LPS-induced AKI.

Hypobaric Hypoxia Aggravates Renal Injury by Inducing the Formation of Neutrophil Extracellular Traps through the NF-κB Signaling Pathway

The hypersensitivity of the kidney makes it susceptible to hypoxia injury. The involvement of neutrophil extracellular traps (NETs) in renal injury resulting from hypobaric hypoxia (HH) has not been reported. In this study, we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism. A total of 24 SD male rats were divided into three groups (n=8 each): normal control group, hypoxia group and hypoxia+pyrrolidine dithiocarbamate (PDTC) group. Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters (oxygen partial pressure about 6.9 kPa) for 7 days. PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days. Pathological changes of the rat renal tissues were observed under a light microscope; the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cell-free DNA (cf-DNA) and reactive oxygen species (ROS) were measured; the expression levels of myeloperoxidase (MPO), citrullinated histone H3 (cit-H3), B-cell lymphoma 2 (Bcl-2), Bax, nuclear factor kappa B (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in rat renal tissues were detected by qRT-qPCR and Western blotting; the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining. After hypoxia, the expression of NF-κB protein in renal tissues was significantly increased, the levels of SCr, BUN, cf-DNA and ROS in serum were significantly increased, the formation of NETs in renal tissues was significantly increased, and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues. When PDTC was used to inhibit NF-κB activation, NETs formation in renal tissue was significantly decreased, the expression level of Bcl-2 in renal tissues was significantly increased, the expression level of Bax was significantly decreased, and renal injury was significantly alleviated. HH induces the formation of NETs through the NF-κB signaling pathway, and it promotes apoptosis and aggravates renal injury by decreasing Bcl-2 and increasing Bax expression.

Fufang Shenhua tablet inhibits renal fibrosis by inhibiting PI3K/AKT

BackgroundFufang Shenhua tablet (SHT), a traditional Chinese medicine compound, has been utilized in the clinical management of chronic kidney disease (CKD) for a long time. Nevertheless, the fundamental active constituents and potential mechanism of action remain unclear. Thus, the objective of this study was to investigate the renoprotective effect of SHT on residual renal tissue in CKD model rats and to explore its primary efficacious components and their underlying mechanism. MethodsAfter a 12-week period of SHT treatment through gavage in a 5/6 nephrectomized animal model of CKD, we evaluated the body weight, renal function, and renal pathological changes. Furthermore, the expression levels of fibronectin (FN), collagen I (COL-1), α-smooth muscle actin (α-SMA), and vimentin in renal tissues were assessed. In addition, network pharmacology analysis and molecular docking were utilized to predict the primary active components, potential therapeutic targets, and intervention pathways through which SHT could potentially exert its anti-kidney fibrosis effects. Subsequently, these predictions were validated in renal tissues of rats with CKD and in transforming growth factor β1 (TGF-β1)-induced HK-2 cells. ResultsSHT significantly improved renal function and reduced renal pathological damage and fibrosis in CKD model rats. Network pharmacological analysis identified 62 active components in SHT, with quercetin ranked first, and 105 protein targets shared by SHT and CKD. Based on the protein‒protein interaction network (PPI) and the SHT-CKD-pathway network, AKT1, MYC, IL2, and VEGFA were identified as key targets. Furthermore, GO and KEGG pathway enrichment analyses indicated that the renoprotective effect of SHT on CKD was closely associated with the PI3K/AKT signaling pathway. Molecular docking results demonstrated that the main active components of SHT had a strong binding affinity to the hub genes. During experimental validation, SHT hindered the activity of the PI3K/AKT signaling pathway in the renal tissue of CKD model rats. Furthermore, activation of the PI3K/AKT signaling pathway was correlated with a modified fibrotic phenotype in rats with 5/6 nephrectomy-induced CKD and TGF-β1-induced HK-2 cells. Conversely, SHT and quercetin curtailed the activation of the PI3K/AKT signaling pathway and inhibited the formation of renal fibrosis, thus indicating that the PI3K/AKT signaling pathway is the basis of the antifibrotic effects of SHT. Ultimately, administration of the PI3K/AKT agonist 740Y-P counteracted the fibrotic phenotype of TGF-β1-induced HK-2 cells induced by SHT. ConclusionsIn this investigation, we employed a fusion of systems pharmacology and in vivo and in vitro experiments to elucidate the mechanism of SHT's antifibrotic properties via obstruction of the PI3K/AKT signaling pathway. Additionally, we surmised that AKT may be the principal target of SHT for the management of CKD and that quercetin may be its efficacious component. We have thus identified SHT as a promising drug for the amelioration of renal fibrosis and the progression of CKD.

Noninvasive Assessment of Renal Fibrosis of Chronic Kidney Disease in Rats by [68Ga]Ga-FAPI-04 Small Animal PET/CT and Biomarkers

Renal fibrosis is the most common pathological feature and common pathway of progression in chronic kidney disease (CKD). We evaluated [68Ga]Ga-FAPI-04 small animal positron emission tomography/computed tomography (PET/CT) and biomarkers as noninvasive assessments of renal fibrosis (RF) in CKD rats to generate new ideas for clinical diagnosis. A rat model of renal fibrosis was administered adenine by gavage (n = 28), and the control group was given 0.9% NaCl by gavage (n = 20). At different time points (weeks 1, 2, 4, and 6), five rats were randomly selected from the two groups for [68Ga]Ga-FAPI-04 small animal PET/CT imaging. At the same time, the expression of Fibroblast activation protein (FAP) in renal tissue and the expression levels of type III procollagen N-terminal peptide (PIIINP), transforming growth factor (TGF-β1), Klotho, and sex-determining region Y-box protein 9 (SOX9) in blood and urine were determined. FAP was highly expressed in the renal tissue of rats in the CKD group and expression increased with the progression of renal fibrosis. [68Ga]Ga-FAPI-04 small animal PET/CT examination showed that the uptake of radioactive tracers in the CKD group was higher than that in the control group, and SUVmax (r = 0.9405) and target-to-background ratio (TBR) (r = 0.9392) were positively correlated with renal fibrosis. The serum levels of PIIINP, TGF-β1, and SOX9 in CKD rats were significantly higher than those in the control group and were positively correlated with RF (r = 0.8234, r = 0.7733, and r = 0.7135, respectively) and SUVmax (r = 0.8412, r = 0.7763, and r = 0.6814, respectively). Compared with the control group, the level of serum Klotho decreased and was negatively correlated with RF (r = -0.6925) and SUVmax (r = -0.6322). Compared with the control group, the levels of PIIINP and TGF-β1 in urine were positively correlated with RF (r = 0.8127 and r = 0.8077, respectively) and SUVmax (r = 0.8400 and r = 0.8177, respectively). Urine Klotho decreased compared with the control group and was negatively correlated with RF (r = -0.5919) and SUVmax (r = -0.5995). The change in urine SOX9 was not statistically significant. In conclusion, compared with renal biopsy, [68Ga]Ga-FAPI-04 small animal PET/CT shows renal fibrosis quickly and noninvasively. PIIINP, TGF-β1, and Klotho in serum and urine may be used as biomarkers of RF, and serum SOX9 is expected to become a new diagnostic biomarker of RF.

Role of Bone Marrow Mesenchymal Stem Cells in p38MAPK Signaling Pathway and Extracellular Matrix Accumulation in Renal Tissue of Focal Segmental Glomerulosclerosis

BMSCs can effectively reduce the accumulation of extracellular matrix in renal tissues of rats with FSGS. This study intends to investigate the effect of BMSCs on extracellular matrix accumulation in renal tissues of rats with FSGS. 60 female mice aged 3 weeks were randomly assigned into control group, model group, transplantation group, positive control group and p38MAPK signaling pathway agonist group (agonist group) followed by analysis of renal histopathology, body weight, kidney weight and renal weight index of rats, expression of Col-IV, FN, MMP-9 protein and mRNA, as well as P38MAPK, P-CREB protein expression. The body weight, kidney weight and kidney weight index of rats in control group, transplant group and positive control group were significantly lower than those in model group and agonist group (P < 0.05) without differences among control group, transplantation group, positive control group, model group and agonist group (P > 0.05). COL-IV and FN protein and mRNA expression was higher in control group, transplantation group and positive control group, while MMP-9 expression was lower. However, agonist group and model group showed opposite profile of these proteins (P < 0.05). The protein expressions of p38MAPK and P-CREB in control group and transplantation group were lower than those in model group, positive control group and agonist group (P < 0.05) without significant difference among other groups (P > 0.05). In conclusion, BMSCs can reduce the accumulation of extracellular matrix and glomerular sclerosis, thereby controlling FSGS progress.

Bushen Huoxue Recipe Inhibits Renal Fibrosis by Regulating the Reactive Oxygen Species/Nucleotide-Binding Oligomerization Domain-Like Receptor Family Pyrin Domain-Containing 3-Induced Pyroptosis Pathway

To probe the role and specific mechanism of Bushen Huoxue Recipe in inhibiting renal fibrosis (RF), 150 healthy adult male Sprague-Dawley rats were randomized to sham operated group (SO group), model group (UUO group), conventional treatment group (UUO+EPL group), high-dose Bushen Huoxuefang group (UUO+H group), and low-dose Bushen Huoxue Recipe group (UUO+L group), with 30 mice in each group. The UUO, UUO+EPL, UUO+H, and UUO+L groups showed decreased pathological damage scores in rat renal tissue and increased blood urea nitrogen (BUN), serum creatinine (Cr), interleukin-1β (IL-1β), IL-18, high-sensitivity C-reactive protein (hs-CRP), and caspase-1 levels compared with the SO group. The expression of NLRP3, type III collagen (Col-III), matrix fibronectin (FN), and α-smooth actin (α-SMA) increased (P <0.05). Inflammatory cells aggregated in rat kidney tissue, and some renal tubular cells atrophied, fell off, vacuolized, underwent pyknosis, and the shape of tubules was incomplete. The lumen was enlarged, and the DNA damage was greater. The UUO+EPL, UUO+H and UUO+L groups showed increased pathological damage score of rat renal tissue and decreased expression levels of Cr, BUN, hs-CRP, IL-1β, IL-18, caspase-1, NLRP3, FN, Col-III, and α-SMA than UUO group. After a longer period, the UUO+EPL and UUO+H groups decreased more significantly than the UUO+L group. We conclude that Bushen Huoxue Recipe inhibits RF by regulating reactive oxygen species (ROS)/NLRP3-induced pyroptosis pathway.

Anti-inflammatory and anti-apoptotic potential of beta-glucan on chemotherapy-induced nephrotoxicity in rats

Background/Aim: Cyclophosphamide (CP) is an anti-cancer agent that mediates nephrotoxicity. Beta (β)-glucan has restorative effects on kidney toxicities through its antioxidant potential; however, the effects of β-glucan on CP-induced renal injury remain unknown. In an experimental nephrotoxicity model using rats, we sought to examine the potential protective action of β-glucan on kidney histomorphology, apoptosis, and TNF-α expression. Methods: Male albino Wistar rats were divided equally into four groups: control, CP, β-glucan, and CP+β-glucan. The kidney tissues of the rats were examined for TNF-α and caspase-3 immunostaining to evaluate inflammation and apoptosis, respectively. Hematoxylin and eosin (H&E) and periodic acid–Schiff (PAS) staining were used for histopathological analyses. Results: The CP group showed severe histopathological damage in the renal tissues of rats. In the renal tissue of the CP group, immunoreactivities for TNF-α (1.25 [0.079] and caspase-3 (1.506 [0.143] were also higher than the control group (0.117 [0.006] and 0.116 [0.002], respectively; P<0.001). In the CP+β-glucan group, the histopathological changes significantly improved. Conclusion: Beta-glucan has therapeutic potential against CP-induced nephrotoxicity in rat kidney.

Effects of drugs commonly used in Sars-CoV-2 infection on renal tissue in rats

Aim: In December 2019, the coronavirus disease was caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Some drugs were repurposed for this disease treatment. Hydroxychloroquine (HCQ), favipiravir (FAV), molnupiravir (MOL), and dexamethasone (DEX) were widely used for the treatment of the disease. To increase the success of the treatment of coronavirus disease, there was used some of these drugs in combination. On the other hand, limited studies report these drugs’ side effects. Therefore, this study was designed to evaluate the possible effects of these drugs and their combinations on the kidney tissues of rats without viral load. Materials and Methods: Male Wistar albino rats were divided into control, HCQ, FAV, HCQ+FAV, HCQ+FAV+DEX, MOL, and MOL+DEX groups. At the end of the experiment, the serum kidney tissue samples were taken. Serum samples were analyzed for urea and creatinine. Kidney tissue samples were assessed as histopathological and immunohistochemical for heat shock protein 60 (HSP60), caspase-3, and receptor-interacting protein kinase-3 (RIPK3). Results: Urea and creatinine levels were within the normal range in all groups. Histopathologically, all drugs and their combinations caused tubular degeneration. On the other hand, histopathological alterations were more prominent in the HCQ group. The oxidative stress marker HSP60 was significantly increased in FAV, MOL, and MOL+DEX groups, while it was similar to the control group in the HCQ groups. Apoptosis marker caspase-3 expression was found to be prominently higher in other drug groups except the FAV group. Expression of RIPK3, a marker of necroptosis, was significantly increased in all drug groups. Conclusion: Taken together, the data of our study show that the administration of all drugs alone and in combination may cause structural damage to the kidney. Furthermore, our results indicate that HCQ can exhibit more damaging effects compared to other drugs.

Hyperoside Ameliorates Renal Tubular Oxidative Damage and Calcium Oxalate Deposition in Rats through AMPK/Nrf2 Signaling Axis.

Nephrolithiasis is a common disease that seriously affects the health and life quality of patients. Despite the reported effect of hyperoside (Hyp) against nephrolithiasis, the specific mechanism has not been clarified. Therefore, this study is aimed at investigating the effect and potential mechanism of Hyp on renal injury and calcium oxalate (CaOx) crystal deposition. Rat and cell models of renal calculi were constructed by ethylene glycol (EG) and CaOx induction, respectively. The renal histopathological damage, CaOx crystal deposition, and renal function damage of rats were assessed by HE staining, Pizzolato staining, and biochemical detection of blood and urine parameters. MTT and crystal-cell adhesion assays were utilized to determine the activity of HK-2 cells and crystal adhesion ability, biochemical detection and enzyme-linked immunosorbent assay (ELISA) to measure the levels of oxidative stress-related substances and inflammatory factors, and western blot to test the expression levels of proteins related to the AMPK/Nrf2 signaling pathway. Briefly speaking, Hyp could improve the renal histopathological injury and impaired renal function, reduce the deposition of CaOx crystals in the renal tissue of rats with renal calculi, and decrease the adhesion of crystals to CaOx-treated HK-2 cells. Besides, Hyp also significantly inhibited oxidative stress response. Furthermore, Hyp was associated with the downregulation of malondialdehyde, lactate dehydrogenase, and reactive oxygen species and upregulation of superoxide dismutase activity. Additionally, Hyp treatment also suppressed inflammatory response and had a correlation with declined levels of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor. Further exploration of mechanism manifested that Hyp might play a protective role through promoting AMPK phosphorylation and nuclear translation of Nrf2 to activate the AMPK/Nrf2 signaling pathway. Hyp can improve renal pathological and functional damage, decrease CaOx crystal deposition, and inhibit oxidative stress and inflammatory response. Such effects may be achieved by activating the AMPK/Nrf2 signaling pathway.

A histological investigation of the influence of Naringin on acetaminophen-induced nephrotoxicity in male albino rats

A study was conducted to examine the protective effects of naringin (NRG) on renal tissues of rats, specifically against acetaminophen (ACN)-induced damage. Thirty-two male rats were included in the study, divided into four groups. The first group (group I) was administered 1 ml/kg of saline orally, serving as the control group. The second group received 2g/kg of ACN on the first day. The third group received a single oral dose of 2g/kg of ACN on the first day, followed by 40 mg/kg of oral NRG for eight consecutive days. Lastly, the fourth group was given a single oral dose of 2g/kg of ACN on the first day, followed by 80 mg/kg of oral NRG for eight days. The rats were then euthanized and their kidneys were removed after they had been anesthetized for blood collection. The ACN-induced renal damage was characterized by significant reductions in body weight, levels of superoxide dismutase (SOD), and catalase. Additionally, there were significant increases in kidney weight, serum creatinine, blood urea nitrogen, serum uric acid, malondialdehyde enzyme (MAD), and histopathological alterations. The study demonstrated that NRG treatment at doses of 40 and 80 mg/kg b.w. effectively reduced renal toxicity and oxidative damage induced by ACN. The effectiveness of these improvements was demonstrated by the noticeable increase in body weight, elevated levels of SOD and CAT, as well as the reduction in kidney weight, CR, BUN, SUA, and MAD levels. As a result of these findings, NRG is confirmed to have antioxidant properties and be capable of protecting rats from renal toxicity caused by ACN.

Does Omeprazole, the Proton-Pump Inhibitor, Affects the Structure of the Kidney of Male Albino Rats? Histological and Laboratory Study.

This study was done to assess the injurious effects of omeprazole by an in vivo experimental study on rat kidneys. Forty-two adult male albino rats were divided into four groups: Control group (I) in which rats were not administrated any treatment. In Groups IIa, IIb, and IIc rats received daily oral omeprazole in dose of 0.75 mg per kg for 2, 4, and 6 weeks, respectively. At the end of the experiment, blood samples were collected for serum creatinine and blood urea nitrogen measurement. Then, animals were sacrificed, and kidney specimens were processed for paraffin blocks, sectioned and stained with H and E, Mallory trichrome and Periodic acid-Schiff, then examined by the light microscope. Stained sections and image analysis were used to count vacuolated cells, pyknotic nuclei, tubular casts, and area percent of collagen fiber deposition, and then, data were subjected to the statistical analysis. Examination of omeprazole-treated groups showed injury of renal corpuscles, renal tubules, and vascular congestion with inflammatory cell infiltrate in renal interstitium. Thickening of basement membrane with deposition of collagen fibers was also detected. Statistically significant increase in the number of vacuolated cells, pyknotic nuclei, hyaline casts, and area percentage of collagen fiber deposition as compared with the control group was noticed, with deterioration of renal function tests. It was concluded that the long-term use of omeprazole resulted in structural damage of rat renal tissue associated with deterioration of renal function in a time-dependent manner.

Rosiglitazone attenuates hypoxia-induced renal cell apoptosis by inhibiting NF-κB signaling pathway in a PPARγ-dependent manner

Background In recent years, peroxisome proliferator-activated receptor γ (PPARγ) has been found to be closely associated with hypoxia renal disease. The aim of this study was to investigate the relationship between rosiglitazone and mitochondrial apoptosis in renal tissue and its associated mechanisms. Methods Twenty-four male Sprague-Dawley rats were randomly divided into three groups (n = 8 in each): normal control group, hypoxia injury group (equal volume of 0.9% saline), and PPARγ agonist group (Rosiglitazone, 10 mg/kg · d, intraperitoneally). The hypoxia injury group and PPARγ agonist group were placed in a hypoxia chamber and the simulated altitude was set at 7,000 m for 7 days. Blood and kidney samples were collected after 7 days. The quantitative real-time polymerase chain reaction and Western blot methods were used to determine the expression of PPARγ, nuclear factor kappa-B (NF-κB), B-cell lymphoma-2 (Bcl-2), and Bax. Results The results showed that compared with the normal control group, the renal tissue of rats after hypoxia was severely damaged, as shown by massive renal tubular epithelial cell degeneration and detachment, and renal tubular dilation. The NF-κB protein expression significantly increased, the Bcl-2 protein and mRNA expression significantly decreased, and Bax protein and mRNA expression significantly increased (p < .05 for all). Renal injury was much less severe in the PPARγ agonist group compared to the hypoxia injury group. Conclusions Rosiglitazone can alleviate hypoxia renal injury, with the possible mechanism involving attenuation of apoptosis by inhibiting the activation of the NF-κB signaling pathway in a PPARγ-dependent manner and increasing Bcl-2 and decreasing Bax expression.

Effect of Taraxacum officinale L. ethanol extract against kidney injuries induced by paracetamol in rats

Background/Aim: The biochemical effects of dandelion (D) ethanol extract on blood and renal tissue in rats induced by paracetamol (PRC) were examined in this study. Methods: In this study was utilized 36 Sprague Dawley male rats, aged 5 months. Rats were divided 6 groups of 6 rats each, randomly. Control group (C), D200 group, D250 group, PRC group, PRC+D200 group, PRC+D250 group, was given orally per os (p.o) in a single dosage (2 g/kg/b.w.) and dandelion extract (200-250 mg/kg) was given intraperitoneally (i.p) for 8 days. Results PRC raised plasma levels of urea, uric acid, and creatinine, as well as malondialdehyde, nitrate, and nitrite in kidney tissue. Furthermore, antioxidant levels/activities in renal tissue were reduced. Dandelion reduced plasma levels of urea, uric acid, and creatinine, as well as lipid peroxidation, nitrat, and nitrit in kidney tissue, while simultaneously increasing antioxidant activities. Conclusion: In this study was investigated that dandelion ethanol extract can be used excellent protection against PRC damage.

Effects of astragaloside IV on delaying kidney aging and its mechanisms

To investigate the mechanisms of Astragaloside Ⅳ on inhibiting apoptosis and delaying kidney aging in rats by regulating SIRT1/p53 signaling pathway. The aging model was established by subcutaneous injection of D-galactose 200 mg/(kg·d). SPF-grade healthy male SD rats were randomly divided into 4 groups: normal control group (intragastric infusion of 5 ml/(kg·d) normal saline), aging model group (intragastric infusion of 5 ml/(kg·d) normal saline), Astragaloside IV group (intragastric infusion of 40 mg/(kg·d) Astragaloside IV),and SRT1720 group( intragastric infusion of 20 mg/(kg·d) SRT1720), with 10 rats in each group. After 8 weeks, the serum samples of rats were collected to detect the levels of renal function (creatinine and urea nitrogen) and senescent associated secretory phenotype (TGF-β and IL-6) by ELISA. The renal tissues of rats were obtained for HE and Masson staining. The protein and mRNA expressions of SIRT1, p53, Bcl-2, Bax, p21 and pRb were detected by Western blot and RT-PCR. Serum creatinine and urea nitrogen levels in the aging model group were higher than those in the normal group, but there was no significant difference in each group (P＞0.05). The serum levels of TGF-β and IL-6 in the aging model group were higher than those in the normal group (P＜0.05), and which in the Astragaloside IV group and SRT1720 group were lower than those in the model group (P＜0.05). There was no significant differences between Astragaloside IV group and SRT1720 group (P＞0.05). The results of pathological staining of renal tissues showed that, compared with the normal group, the renal tubules dilated, local atrophy, infiltration of inflammatory cells and proliferation of collagen fibers were observed in the aging model group. Compared with the aging model group, the pathological changes were alleviated in Astragaloside IV group and SRT1720 group. The results of Western blot and RT-PCR showed that, compared with the normal group, the protein and mRNA expressions of SIRT1 and pRb in the renal tissue of the aging group were decreased, the protein expression of Bcl-2 was decreased(P＜0.05), and the protein and mRNA expressions of p53 and p21 were increased, the protein expression of Bax was increased(P＜0.05). Compared with the aging group, Astragaloside IV and SRT1720 improved the above-mentioned indexes (P＜0.05). Astragaloside IV can delay kidney aging by regulating the SIRT1/p53 signaling pathway.

Ultrastructural changes in renal tissue in rats with renal failure under the influence of herbal composition BNO 2103

Management of chronic kidney disease is an urgent task of the global health care system, as untreated, it leads to partial or permanent loss of kidney function. Standardized herbal remedies are highly effective and relatively safe. That is why it is suggested to pay attention to herbal remedies already known for the treatment of genitourinary diseases to expand the indications for their use. The aim of the research is to study the nephroprotective properties of the standardized herbal composition BNO 2103, which is the active ingredient of Canephron N ®, in a model of renal failure in rats. Materials and methods. An experimental study was performed on 42 male white outbred rats weighing 150–200 g, which were divided into 4 groups. Nephropathy was induced by a single subcutaneous injection of 0.7 ml/kg of 2.5 % potassium chromate solution. Animals in 3 and 4 groups received BNO 2103 at a dose of 33.0 mg/kg and prednisolone at a dose of 1.9 mg/kg intragastrically daily for 20 days. After animals were sacrificed, their kidneys were obtained and studied with standard electronic microscopy methods. Results. BNO 2103 normalized the ultrastructural picture of the kidneys, however, with the presence of minor pathological signs. BNO 2103 reduced the destruction of basement membranes, improved organelle structure and increased metabolic processes in podocytes, and endotheliocytes, reducing the manifestations of degenerative-dystrophic changes in them. BNO 2103 was superior to the reference drug prednisolone. Conclusions. BNO 2103 showed a significant nephroprotective effect, normalizing the ultrastructural picture of the kidneys in rats with renal failure. This effect is most likely related to the presence of biologically active substances with a powerful antioxidant, anti-inflammatory, nephroprotective activity. The obtained results allow us to consider BNO 2103 as a promising nephroprotective agent for the treatment of chronic kidney disease.

High Doses of Anacardium Occidentale Nut Shell Extract Induce Oxidative Damage in Cardiac and Renal Organs of Wistar Rats

Anacardium occidentale (Cashew) is a plant reported to show several biological activities. The aim of this study is to examine the effects of methanol extract of Anacardium occidentale nut shell on the antioxidant status and histological features in cardiac and renal tissues of rats. Shells were obtained from the nut, air-dried, pulverized, and subjected to Soxhlet extraction to obtain Anacardium occidentale nut shell extract (AONSE). Forty-five male Wistar rats were divided into nine groups (5 rats each), and given oral gavage of corn oil (Control), and 50, 100, 150, 200, 250, 300, 350 and 400 mg/kg of AONSE, every other day for twenty-eight days. After sacrifice, heart and kidney were removed and divided into two portions each; one portion was homogenized for biochemical assays, while the other was fixed in formalin for histopathology. Superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and Malondialdehyde (MDA) levels in the two organs were spectrophotometrically assayed. Histopathology of the organs was also done. The SOD and catalase were reduced in heart at high doses of AONSE relative to control. The AONSE has no significant effects on GPx, GST and MDA in the two organs, comparable to control. Photomicrographs of heart show, myocardial distortions and fibrosis, while glomerular fluid accumulation and hemorrhagic fibrosis were observed in kidney, at high doses, as against control and low doses of AONSE. This study shows that high doses of Anacardium occidentale nut shell extract could induce cytological derangements in heart and kidney of rats, possibly via oxidative mechanism.

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.

The Effect and Mechanism of New Processing Method of Codonopsis pilosula on Endocrine Physique Index in Rats.

Objective To explore the effect and mechanism of a new processing method of Codonopsis pilosula (CP) on the endocrine physique index in rats. Methods The rats were randomly assigned into the control group, model group, CP group (3.75 g/kg crude drug), rice-fried CP group (3.75 g/kg crude drug), and honey-roasted CP group (3.75 g/kg), with 10 rats in each group. All rats were gavaged according to the body weight of 1 mL/100 g every morning for 3 weeks. The water extracts of different processed products of CP were given to the drug group, the blank group, and the model group which were given the same volume of normal saline during the experiment. The model group and each administration group were fed every other day and drank freely for 21 days, during which the weight was weighed every 2 days. The changes of the organ index; the contents of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), adrenocorticotropic hormone (ACTH), and cortisol (Cor); and the activity of sodium and potassium adenosine triphosphate (Na+K+-ATP) were measured by enzyme-linked immunosorbent assay (ELISA). The expression of aquaporin-1 (AQP1) and aquaporin-2 (AQP2) mRNA was detected by RT-PCR. Results Effect on the organ index: the organ index of the control group, CP group, rice-fried group, and honey moxibustion group was higher compared to that of the model group, and the organ index of the honey moxibustion group was the highest (P < 0.05). The level of cAMP and the ratio of cAMP/cGMP in the model group were significantly higher compared to those of the control group (P < 0.05); CGMP in the model group decreased significantly (P < 0.05). Compared with the model group, the level of cAMP in the CP group, rice-fried group, and honey moxibustion group decreased significantly, while the ratio of cGMP and cAMP/cGMP increased significantly (P < 0.05). Compared with the CP group, rice-fried group, and honey moxibustion group, the level of cAMP and the ratio of cAMP/cGMP in the honey moxibustion group were lower compared to those in the other two groups, and the ratio of cGMP in the honey moxibustion group was higher compared to that in the other two groups (P < 0.05). The contents of ACTH and Cor in the model group were significantly higher compared to those in the control group (P < 0.05). Compared with the model group, the contents of ACTH and Cor in the CP group, rice-fried group, and honey moxibustion group were significantly lower compared to those in the model group (P < 0.05). Compared with the CP group, rice-fried group, and honey moxibustion group, the contents of ACTH and Cor in the honey moxibustion group were higher compared to those in the other two groups (P < 0.05). The content of the Na+K+-ATP enzyme in the model group was significantly higher compared to that in the control group (P < 0.05). Compared with the model group, the content of the Na+K+-ATP enzyme in the CP group, rice-fried group, and honey moxibustion group decreased significantly (P < 0.05). Compared with the CP group, rice-fried group, and honey moxibustion group, the content of the Na+K+-ATP enzyme in the honey moxibustion group was higher compared to that in the other two groups (P < 0.05). The expression of AQP1 and AQP2 mRNA in the kidney tissue of the kidney yin deficiency model group was significantly higher compared to that of the control group (P < 0 05). Compared with the model group, the expression levels of AQP1 and AQP2 mRNA in the renal tissue of rats in the CP group, rice-fried group, and honey moxibustion group decreased in different degrees (P < 0.05). There was no statistical difference between the CP group, rice stir-frying group, and honey moxibustion group. Conclusion This study proves that the new processing method of CP can improve the endocrine physique index of rats, enhance their organ quality, and regulate the disorder of water metabolism in kidney yin deficiency syndrome and has a certain therapeutic effect on kidney yin deficiency syndrome. Different new processing methods of CP have different effects on promoting endocrine physique indexes of rats. It is concluded that honey-roasted CP has the best effect on promoting spleen deficiency, which may be through glucose metabolism, amino acid metabolism, and nucleotide metabolism, increasing ATP energy metabolism, so as to strengthen the symptoms of spleen deficiency in rats. The experimental data of this study indicate that the effect of honey-roasted CP is better compared to that of other processed products, which provides an experimental basis for the rational clinical application of the new processed products.

Rhein Inhibits NF-κB Signaling Pathway to Alleviate Inflammatory Response and Oxidative Stress of Rats with Chronic Glomerulonephritis.

Objective To explore the effect and mechanism of rhein on chronic glomerulonephritis (CGN). Method Twenty-four eight-week-old male SD rats were randomly divided into following 4 groups (6 rats in each group): control group, CGN group, rhein group, and benazepril (Ben) group. And 5 mg/mL of cationization-bovine serum albumin (C-BSA) was mixed with an equal volume of Freund's incomplete adjuvant for the preparation of 2.5 mg/mL of C-BSA solution. The rat model of CGN was established by injection of C-BSA for six weeks. Calculation of the renal index in rats was conducted. Biochemical detection was performed to measure the level of 24 h urinary protein, blood urea nitrogen (BUN), serum creatinine (SCr), and serum albumin (ALB) of the rats, as well as the level of malondiadehyde (MDA), superoxide (SOD), and glutathione peroxidase (GSH-Px) in the kidney tissue. Hematoxylin and eosin (H&E) staining was utilized to measure histological changes in the kidney of the rats. The level of TNF-α, IL-1β, IL-6, and ICAM-1 in rat kidney tissues was determined by enzyme-linked immunosorbent assay (ELISA). Western blot was applied to check the expression of NF-κB in the nucleus and cytoplasm as well as the expression of IκBα and p-IκBα in rat kidney tissues. Results Rhein could decline urinary protein, restore blood biochemical parameters, and protect renal tissue in rats with CGN. Besides, rhein could inhibit the activity of the NF-κB signaling pathway in rats with CGN and could alleviate the inflammatory response and oxidative stress level at the same time. Conclusion Rhein alleviates inflammatory responses and oxidative stress in rats with CGN. It also provides a theoretical basis and data support for the therapeutic drugs for CGN.