Renal Histopathological Changes Research Articles

Transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) ameliorates sepsis-associated acute kidney injury by maintaining mitochondrial homeostasis and improving the mitochondrial function.

Mitochondrial dysfunction has a role in sepsis-associated acute kidney injury (S-AKI), so the restoration of normal mitochondrial homeostasis may be an effective treatment strategy. Transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) is a main regulator of cell-redox homeostasis, and recent studies reported that NRF2 activation helped to preserve mitochondrial morphology and function under conditions of stress. However, the role of NRF2 in the process of S-AKI is still not well understood. The present study investigated whether NRF2 regulates mitochondrial homeostasis and influences mitochondrial function in S-AKI. We demonstrated activation of NRF2 in an in vitro model: lipopolysaccharide (LPS) challenge of ductal epithelial cells of rat renal tubules (NRK-52e cells), and an in vivo model: cecal ligation and puncture (CLP) of rats. Overexpression of NRF2 attenuated oxidative stress, apoptosis, and the inflammatory response; enhanced mitophagy and mitochondrial biogenesis; and mitigated mitochondrial damage in the in vitro model. In vivo experiments showed that rats treated with an NRF2 agonist had higher adenosine triphosphate (ATP) levels, lower blood urea nitrogen and creatinine levels, fewer renal histopathological changes, and higher expression of mitophagy-related proteins [PTEN-induced putative kinase 1 (PINK1), parkin RBR E3 ubiquitin protein ligase (PRKN), microtubule-associated protein 1 light chain 3 II (LC3 II)] and mitochondrial biogenesis-related proteins [peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α) and mitochondrial transcription factor A (TFAM)]. Electron microscopy of kidney tissues showed that mitochondrial damage was alleviated by treatment with an NRF2 agonist, and the opposite response occurred upon treatment with an NRF2 antagonist. Overall, our findings suggest that mitochondria have an important role in the pathogenesis of S-AKI, and that NRF2 activation restored mitochondrial homeostasis and function in the presence of this disease. This mitochondrial pathway has the potential to be a novel therapeutic target for the treatment of S-AKI.

Demethylzeylasteral reduces the level of proteinuria in diabetic nephropathy: Screening of network pharmacology and verification by animal experiment.

This study aimed to use network pharmacology to detail the natural components isolated from Triptergium wilfordii Hook F (TwHF) and examine the effect of the main component (demethylzeylasteral, DEM) on rat models of diabetic nephropathy (DN). In this study, we used network pharmacology to detail the natural components isolated from TwHF, referenced a gene library when screening for components effective in the management of DN, and DEM was confirmed in DN rats. All data were analyzed using the Discovery Studio 4.5 System and the systems Dock online docking method platform. All 24 rats were divided into 4 groups: control, DN, TwHF, and DEM. Blood and urine samples were tested at 0, 8, and 12 weeks. Renal histopathological changes were scored. Network pharmacology indicated that 370 compounds and 46 small molecules (including DEM) were biologically active constituents of TwHF, mainly affecting the inflammatory response through PI3K‐Akt and Jak–STAT pathways. Proteinuria in the TwHF and DEM groups was significantly lower than in the DN group (p ≤ .001), and the decrease in proteinuria in the DEM group was more obvious than in the TwHF group (p = .004). The tubular interstitial scores were better in the DEM group than in the TwHF and DN groups. These results indicate that DEM effectively reduced proteinuria and alleviated the tubular interstitial changes in rat models of DN, which may be provide a scientific foundation for the development of novel drugs for treatment of DN.

Pilot testing for long-term impact of glycerol-induced acute kidney injury on oxalate homeostasis in rats

Abstract. There is a general lack of research on the long-term effects of acute kidney injury (AKI) on oxalate-degrading bacteria (ODB) and their total oxalate-degrading activity (ODA) in fecal microbiota. In the present pilot study, we separately evaluated the changes in the ODB number and their total ODA in fecal microbiota at 3-time points after glycerol-induced AKI. In addition, we assessed the interactions between AKI-induced renal histopathological changes and ODB, total fecal ODA, and plasma and urine oxalate concentrations in rats.
 Methods. The male Wistar rats (200-300 g, n = 20) on oxalate-free diet were randomly divided into 2 groups. After 24-h of water deprivation, experimental group 1 (n = 10) received an intramuscular injection of 50% glycerol (10 ml/kg of body weight), and group 2 (n = 10) served as a control. The numbers of ODB (incubated in a highly selective Oxalate Medium and determined using the culture method), total fecal ODA and urinary oxalate (UOx) excretion were measured after injection on days 8, 22 and 70. The method of redoximetric titration with a KMnO4 solution was adopted to evaluate total ODA in fecal microbiota. Renal injury was assessed by histopathology examination, serum creatinine plasma oxalic acid (POx) concentration and daily proteinuria levels after removing the animals from the experiment on day 70.
 Results. After glycerol injection on days 8 and 22, no differences were found in the numbers of ODB, their total fecal ODA, and UOx excretion level between the experimental and control groups. However, after AKI initiation on day 70, the numbers of ODB, total fecal ODA, and daily UOx excretion were significantly lower in the experimental group as compared with the control group. In addition, in 10 weeks following AKI, the number of ODB had a direct correlation with UOx excretion and an inverse correlation with POx and serum creatinine concentrations and daily proteinuria. Total ODA in fecal microbiota was directly associated with the percentage of renal interstitial fibrosis and the average glomerular volumes in the experimental rats.
 Conclusions: AKI had long-term negative effects on the quantitative and qualitative characteristics of ODB in fecal microbiota in rats. Moreover, the results of our study confirmed an increasing trend in total fecal ODA according to the aggravation of renal interstitial fibrosis and glomerular volume in rats’ kidneys. Further studies are warranted to gain more insight into the mechanism of oxalate homeostasis impairment in AKI.

Intra-articular versus systemic vancomycin for the treatment of periprosthetic joint infection after debridement and spacer implantation in a rat model.

AimsTreatment outcomes for methicillin-resistant Staphylococcus aureus (MRSA) periprosthetic joint infection (PJI) using systemic vancomycin and antibacterial cement spacers during two-stage revision arthroplasty remain unsatisfactory. This study explored the efficacy and safety of intra-articular vancomycin injections for PJI control after debridement and cement spacer implantation in a rat model.MethodsTotal knee arthroplasty (TKA), MRSA inoculation, debridement, and vancomycin-spacer implantation were performed successively in rats to mimic first-stage PJI during the two-stage revision arthroplasty procedure. Vancomycin was administered intraperitoneally or intra-articularly for two weeks to control the infection after debridement and spacer implantation.ResultsRats receiving intra-articular vancomycin showed the best outcomes among the four treatment groups, with negative bacterial cultures, increased weight gain, increased capacity for weightbearing activities, increased residual bone volume preservation, and reduced inflammatory reactions in the joint tissues, indicating MRSA eradication in the knee. The vancomycin-spacer and/or systemic vancomycin failed to eliminate the MRSA infections following a two-week antibiotic course. Serum vancomycin levels did not reach nephrotoxic levels in any group. Mild renal histopathological changes, without changes in serum creatinine levels, were observed in the intraperitoneal vancomycin group compared with the intra-articular vancomycin group, but no changes in hepatic structure or serum alanine aminotransferase or aspartate aminotransferase levels were observed. No local complications were observed, such as sinus tract or non-healing surgical incisions.ConclusionIntra-articular vancomycin injection was effective and safe for PJI control following debridement and spacer implantation in a rat model during two-stage revision arthroplasties, with better outcomes than systemic vancomycin administration.Cite this article: Bone Joint Res 2022;11(6):371–385.

STUDY THE EFFECTS OF ANADROL OVERDOSE ON KIDNEY IN RAT MODEL

Background: Anadrol is an active androgenic anabolic steroid that has been clinically studied in numerous diseases since the 1960s. It is used in the treatment of anemia and the replacement of male sex steroids. Unfortunately, in attempts to improve physical performance, Anadrol could be misused by athletes, that can lead to poisoning contributes to renal toxicity. The Aim: This study aims to investigate nephrotoxicity of anadrol via assessment of renal injury markers and histopathological study. Materials and methods: A forty male rats, weights about (200-300 gm), aged 8-12 weeks, after acclimatization, the rats were ‎randomly divided into four groups (n=10) : control group (in which all rats were administered normal saline (NS) via oral gavage), anadrol 10 mg/kg group (in which all rats were administered anadrol 10mg/kg via oral gavage), anadrol 20 mg/kg group (in which all rats were administered anadrol 20mg/kg via oral gavage), and anadrol 30 mg/kg group (in which all rats were administered anadrol 30mg/kg via oral gavage), the oral administration had continued for 8 weeks. At the end of study urea & creatinine were measured via chemical analysis. Then renal histopathological study was done. Results: Rats treated with anadrol displayed high level of urea & creatinine, as compared with control group. On the other hand, histopathological study exhibited significant injurious changes in the renal tissue in anadrol groups comparing with control. Conclusion: When given in high doses anadrol results in renal injury, that can be cleared via both elevated levels of renal injury markers and renal histopathological changes.

The Severity of Interstitial Inflammation in the Renal Parenchyma of Albino Rats Is Subjected to the Dose of Heavy Metals.

AimThis study aimed to determine the relationship between irreversible morphological changes in the renal interstitium and the duration of exposure to heavy metals such as copper in albino rats.Materials and methodsAn experimental research design was used to conduct this study from November 2019 to May 2020. All experiments were performed in the Department of Pathology of the Services Institute of Medical Sciences, University of Health Sciences (UHS) (animal house), Lahore, Pakistan. A total of 30 albino rats equally divided into three groups were included in the study. Group I (control) was given tap water and a typical rodent pellet diet. Groups II and III (experimental) were fed with copper (heavy metal) at a dose of 0.15 and 0.30 mg/kg body weight, respectively, for 18 weeks on alternate days. At the end of the experiment, the kidneys were extracted from the rats, stained with hematoxylin and eosin, and processed for histological observation. Renal histopathological changes were evaluated in terms of edema, inflammation, and fibrosis.ResultsThe collected data were analyzed using the Chi-square test, with p < 0.05 considered significant. Renal histopathology in terms of interstitium showed that edema, inflammation, and fibrosis were significantly different in all groups. In Group I, none of the rats had edema, inflammation, and fibrosis, while in Groups II and III, these characteristics were observed; the difference was significant between the experimental and control groups.ConclusionsHeavy metals, such as copper, can induce renal parenchymal changes in a dose-dependent manner, resulting in edema, fibrosis, and inflammation.

Chromatographic Fractionation of Penicillium polonicum Fermentation Metabolites in Search of the Nephrotoxin(s) for Rats.

Complex renal histopathological changes in rats, in silent response to dietary contamination with wheat moulded by a common Penicillium from the Balkans, have long eluded attribution of a causal toxin. So far, water-soluble amphoteric glyco-peptides seem responsible, at least for the nuclear pyknoses in nephron epithelia after several days of dietary exposure. Recently, refined histology analysis has diagnosed pyknosis as apoptosis, and followed the finding through application of medium-pressure liquid chromatography, anion exchange and silica layer chromatography to fractionate a water/alcohol-soluble extract of a fungal fermentation on wheat. Proline was revealed, with other amino acids, in acid hydrolysate of the fermentation extract. Application of mass spectrometry has recognized prominent ions (m/z 550 and 564) correlated with fragmentations consistent with a terminal proline moiety for the putative toxins, coupled with other structural fragments and correlated with apoptosis. Use of 14C-proline in probing Penicillium polonicum fermentation to aid isolation of the new potential toxins, along with application of gel electrophoresis, may further aid characterization of the apoptosis toxin(s). The present focus on proline peptides in mycotoxicosis fits easily with their increasingly recognised pharmacological activity associated with proline’s rigid secondary amine structure, which causes conformational contortion in peptides. Nevertheless, there remains the striking rat renal karyocytomegaly by P. polonicum, for which there is yet no causative mycotoxin.

The relationship between chikungunya virus and the kidneys: A scoping review.

Several atypical forms of chikungunya fever (CHIK) have been described, including neurological, cardiac and renal involvement. These forms may be related to high morbidity and mortality rates. This scoping review based on the PubMed, Scopus, and WOS databases aims to identify and summarise all the available evidence regarding the clinical and histopathological presentations and risk factors associated with kidney injury related to CHIK, as well as the clinical impact. Thus, a total of 54 papers were selected from 1606 initial references after applying the defined inclusion criteria. Data on the association between kidney injury and CHIK are scarce, with studies only conducted in the acute phase of the disease, lacking further characterisation. Kidney injury incidence in hospitalised patients using the Kidney Disease Improving Global Outcomes criteria varies from 21% to 45%, being higher among patients with atypical and severe manifestations. Although acute kidney injury does not seem to be related to viraemia, it may be related to higher mortality. Few studies have described the renal histopathological changes in the acute phase of CHIK, with prevalent findings of acute interstitial nephritis with mononuclear infiltrate, glomerular congestion and nephrosclerosis. Only one study assessed the kidney function of patients in the subacute and chronic phases of CHIK. Additionally, individuals with comorbidities, including chronic kidney disease, may be among those with a greater risk of presenting worse outcomes when affected by CHIK. The results described herein may contribute to better understand the relationship between the kidneys and chikungunya virus.

Gastroprotective, hepatoprotective, and nephroprotective effects of thymol against the adverse effects of acetylsalicylic acid in rats: Biochemical and histopathological studies

Acetylsalicylic acid (Aspirin) has been used for a long time as an antipyretic and analgesic. Nevertheless, aspirin use is associated with severe morbidity and death because of its detrimental impacts on several organs, including the liver, kidneys, and stomach. The current investigation sought to ascertain the influence of thymol in mitigating aspirin-mediated gastric and hepato-renal injury. This was done by 1) evaluating gastric juice volume and pH as well as pepsin and prostaglandin E2 level; 2) measuring serum biochemical parameters and proinflammatory cytokines; 3) determining tissue oxidant/antioxidant status, and 4) identifying a link with gastric, hepatic and renal histopathological changes. Forty-eight rats were segregated to six groups: normal control, Th100, Th200, ASA, Th100 + ASA, Th200 + ASA. Daily administration of aspirin (ASA, 150 mg/kg body weight) for 3 successive days induced a significant increase in gastric juice volume, pepsin activity, serum transaminases, alkaline phosphatase, urea, creatinine, tumor necrosis factor-α, myeloperoxidase, and tissue malondialdehyde levels. In contrast, a significant reduction in gastric pH, prostaglandin E2, tissue non-enzymatic antioxidant (glutathione), and enzymatic antioxidant (superoxide dismutase, glutathione peroxidase, and catalase) levels. These biochemical changes were accompanied by histological modifications that included changes to the normal gastric, hepatic, and renal architectures. Pretreatment and simultaneous oral treatment with thymol (100 or 200 mg/kg body weight) plus ASA significantly improved all biochemical and histological changes in a dose-dependent way. Thymol's antiinflammatory and antioxidative properties may contribute to its protective action. As a result, thymol may represent a promising medication for preventing aspirin-induced gastric, liver, and renal damage.

Oridonin Attenuates Cisplatin-Induced Acute Kidney Injury via Inhibiting Oxidative Stress, Apoptosis, and Inflammation in Mice.

The use of cisplatin, a chemotherapy drug, is often limited due to its renal side effects such as acute kidney injury (AKI). However, there are no validated medications to prevent or treat cisplatin-induced AKI. Oridonin is the major bioactive component of Isodon rubescens (Rabdosia rubescens) and exhibits anticancer, antioxidative, and anti-inflammatory effects. Recent studies have shown that oridonin alleviated a variety of inflammatory diseases, including renal diseases, in rodents. This study was aimed at investigating the potential renoprotective effect of oridonin on cisplatin-induced AKI. Male C57BL/6 mice were administered with cisplatin (20 mg/kg) with or without oridonin (15 mg/kg). Oridonin administration to mice after cisplatin injection attenuated renal dysfunction and histopathological changes. Upregulation of tubular injury markers was also suppressed by oridonin. Mechanistically, oridonin suppressed lipid peroxidation and reversed the decreased ratio of reduced to oxidized glutathione in cisplatin-injected mice. The increase in cisplatin-induced apoptosis was also alleviated by the compound. Moreover, oridonin inhibited cytokine overproduction and attenuated immune cell infiltration in cisplatin-injected mice. Altogether, these data demonstrated that oridonin alleviates cisplatin-induced kidney injury via inhibiting oxidative stress, apoptosis, and inflammation.

Suppression of LMCD1 ameliorates renal fibrosis by blocking the activation of ERK pathway.

Tubulointerstitial fibrosis is a common pathway of chronic kidney disease (CKD) and is closely related to the progression of CKD. LMCD1, acting as an intermediary, has been reported to play a role in cardiac fibrosis. However, its role in renal fibrosis is yet to be deciphered. Based on the GEO database, we found the expression of LMCD1 is increased in kidney tissues of CKD patients and in human proximal tubular epithelial (HK-2) cells treated with transforming growth factor-β1 (TGF-β1), suggesting that LMCD1 may be involved in tubulointerstitial fibrosis. Herein, we investigated the role of LMCD1 in mice with unilateral ureteral obstruction (UUO) and in TGF-β1-stimulated HK-2 cells. In the UUO model, the expression of LMCD1 was upregulated. UUO-induced renal histopathological changes were mitigated by knockdown of LMCD1. LMCD1 silence alleviated renal interstitial fibrosis in UUO mice by decreasing the expression of TGF-β1, fibronectin, collagen I, and collagen III. LMCD1 deficiency suppressed cell apoptosis in kidney to prevent UUO-triggered renal injury. Furthermore, LMCD1 deficiency blocked the activation of ERK signaling in UUO mice. In vitro, LMCD1 was upregulated in HK-2 cells after TGF-β1 stimulation. LMCD1 silence abrogated TGF-β1-mediated upregulation of fibrotic genes. Treatment of HK-2 cells with ERK-specific inhibitor SCH772984 and agonist TPA validated LMCD1 exerted its function via activating ERK signaling. Together, our findings suggest that inhibition of LMCD1 protects against renal interstitial fibrosis by impeding ERK activation.

Green coffee bean extract attenuates gentamicin induced acute nephrotoxicity in rats

Gentamicin induced acute nephrotoxicity (GIAN) is considered as one of the important causes of acute renal failure. In recent years’ great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of GIAN. Hence, the current study was designed to investigate the effect of green coffee bean extract (GCBE) on GIAN in rats. Results of the present study showed that rat groups that received oral GCBE for 7 days after induction of GIAN (by a daily intraperitoneal injection of gentamicin for 7days), reported a significant improvement in renal functions tests when compared to the GIAN model groups. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE-treated groups when compared to GIAN model group. These results indicate that GCBE has a potential role in ameliorating renal damage involved in GIAN.

Exogenous glutathione protects against gentamicin-induced acute kidney injury by inhibiting NF-κB pathway, oxidative stress, and apoptosis and regulating PCNA

This study was designed, for the first time, to examine the possible nephroprotective effects of exogenous glutathione (EGSH) (100 mg/kg, intraperitoneally) on gentamicin-induced acute kidney injury (GM-induced AKI). EGSH reduced renal histopathological changes, inflammatory cell infiltration, and improved renal dysfunction in rats with AKI. EGSH ameliorated GM-induced renal oxidative stress by promoting the renal activities of catalase, glutathione peroxidase, and superoxide dismutase and diminishing renal malondialdehyde and serum nitric oxide levels. Interestingly, EGSH inhibited intrinsic apoptosis by downregulating Bax and caspase-3 and upregulating Bcl2 in the kidney of rats with AKI. EGSH decreased GM-induced inflammatory response as reflected by a remarkable decrease in the protein expressions of NF-κB-p65, IL-6, TNF-α, and iNOS and a considerable diminish in myeloperoxidase activity. Finally, EGSH markedly declined proliferative cell nuclear antigen (PCNA) protein expression in the animals with AKI. In summary, EGSH alleviated AKI in rats intoxicated with GM, partially by inhibiting oxidative stress, NF-κB pathway, and intrinsic apoptosis and regulating PCNA.

Renoprotective effects of Adansonia digitata leaf extract on renal function and histopathological changes in vancomycin-induced nephrotoxicity in Wistar rats

Renoprotective effects of Adansonia digitata leaf extract on renal function and histopathological changes in vancomycin-induced nephrotoxicity in Wistar rats

Correlation of Renal Histopathological Changes, Lymphocytes Infiltration, Caspase-3 and Apoptosis Activation with Diabetic Nephropathy Induced by High Energy Diet in An Experimental Rat Model “Psammomys obesus”

Correlation of Renal Histopathological Changes, Lymphocytes Infiltration, Caspase-3 and Apoptosis Activation with Diabetic Nephropathy Induced by High Energy Diet in An Experimental Rat Model “Psammomys obesus”

Spectrum of Renal Histopathological Changes in Multiple Myeloma

Introduction: Renal involvement is very common in myeloma. The evaluation of renal status plays an important role in diagnosis and prognosis of patients with myeloma. The kidney biopsy will show various patterns of injury and the chronicity of the disease which help in planning the treatment options. Myeloma comprises a significant number of malignancies but no data regarding renal biopsy changes in myeloma is available from North Kerala, India. Aim: To describe the various morphological patterns of renal involvement in all myeloma patients who required a renal biopsy for evaluation of renal dysfunction. Materials and Methods: It was a retrospective, descriptive study conducted at Government Medical College, Kozhikode, a tertiary care centre from January 2016 to December 2019. A total of 63 patients of myeloma who underwent a renal biopsy for evaluation of renal dysfunction as the initial presentation or immediately after diagnosis were included in this study. Serum electrophoresis, skeletal survey, complete blood counts, bone marrow study and biochemical evaluation for serum creatinine, total protein, albumin globulin ratio were done in all patients. Data was analysed using standard analytical techniques with Statistical Package for the Social Sciences (SPSS) version 16.0 for Windows. Results: A total of 63 patients presented with renal dysfunction as initial symptom underwent renal biopsy. Most common age group of the study population was between 50 to 70 years. In 47 patients (74%) the renal dysfunction was the initial presenting symptom of myeloma. The presenting features were acute renal failure, nephrotic syndrome and acute nephritis. The renal biopsy findings included myeloma cast nephropathy, amyloidosis, proliferative glomerulonephritis and tubulointerstitial nephritis with cast nephropathy being most common pattern. Acute renal failure was more common in cast nephropathy while amyloidosis presented with nephrotic syndrome. The serum creatinine and calcium levels, plasma cell counts and degree of anaemia had a correlation with histological pattern of injury. Conclusion: Acute Kidney injury due to myeloma cast nephropathy is a medical emergency and prompt therapy with measures to reduce light chain load along with correction of dehydration can reduce renal damage and increase the patient survival. Many newly described entities like fibrillary and immunotactoid nephropathy can occur in myeloma and these can be identified only by electron microscopic evaluation of kidney tissue. They have important prognostic impact and significance when renal transplants are planned for. So renal biopsy supported by newer methods like immunohistochemistry and electron microscopy is a must to keep pace with newer advances in myeloma treatment like autologous stem cell transplantation.

Methyl Gallate Improves Hyperuricemia Nephropathy Mice Through Inhibiting NLRP3 Pathway.

Hyperuricemia nephropathy (HN) is a form of chronic tubulointerstitial inflammation, caused by the deposition of monosodium urate crystals (MSU) in the distal collecting duct and medullary interstitium, associated with a secondary inflammatory reaction. Numerous published reports indicated that NLRP3 inflammasome pathway play crucial roles in HN symptoms. The present study aims to investigate the protective effects of methyl gallate on HN mice and the underlying mechanisms. An HN model was established by intraperitoneal injection of potassium oxide (PO) to assess the effect of methyl gallate on renal histopathological changes, renal function, cytokine levels and expressions of NLRP3-related protein in HN mice. Moreover, in vitro models of lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs) and human peripheral blood mononuclear cells (PBMCs) were established to explore the mechanism of methyl gallate on NLRP3 inflammasome activation. The results showed that methyl gallate significantly ameliorated HN by inhibiting uric acid production and promoting uric acid excretion as well as ameliorating renal injury induced by NLRP3 activation. Mechanistically, methyl gallate is a direct NLRP3 inhibitor that inhibits NLRP3 inflammasome activation but has no effect on the activation of AIM2 or NLRC4 inflammasomes in macrophages. Furthermore, methyl gallate inhibited the assembly of NLRP3 inflammasomes by blocking the ROS over-generation and oligomerization of NLRP3. Methyl gallate was also active ex vivo against ATP-treated PBMCs and synovial fluid mononuclear cells from patients with gout. In conclusion, methyl gallate has a nephroprotective effect against PO-induced HN through blocking the oligomerization of NLRP3 and then exerting anti-inflammatory activity in the NLRP3-driven diseases.

Jian-Pi-Yi-Shen Formula Alleviates Chronic Kidney Disease in Two Rat Models by Modulating QPRT/NAD+/SIRT3/Mitochondrial Dynamics Pathway

Objective Jian-Pi-Yi-Shen formula (JPYSF) is a traditional Chinese herbal decoction and has been used for treating chronic kidney disease (CKD) in clinics for decades. However, the potential mechanisms have not been fully elucidated. This study was designed to test the efficacy of JPYSF in treating CKD and explore the underlying mechanism. Methods Two CKD rat models were established by 5/6 nephrectomy (5/6 Nx) and feeding with adenine-containing feed, respectively. The intervention dose of JPYSF was 10.89 g/kg/d by gastric irrigation. Renal function was assessed by serum creatinine (Scr) and blood urea nitrogen (BUN). Periodic acid-Schiff (PAS) and Masson's trichrome staining were used to evaluate renal histopathological changes. The levels of nicotinamide adenine dinucleotide (NAD+) were measured by using the enzyme-linked immunosorbent assay kit. The proteins expressions of renal fibrosis, quinolinate phosphoribosyltransferase (QPRT), sirtuin 3 (SIRT3), and mitochondrial dynamics were determined and quantified by Western blot analysis. Results The results show that administration of JPYSF significantly lowered Scr and BUN levels, improved renal tubular atrophy and interstitial fibrosis, and decreased renal extracellular matrix deposition in two CKD rat models. In addition, CKD rats exhibited suppressed QPRT/NAD+/SIRT3 signal, increased mitochondrial fission, and decreased mitochondrial fusion. JPYSF treatment promoted QPRT/NAD+/SIRT3 signal and restored mitochondrial fission/fusion balance. Conclusion In conclusion, administration of JPYSF effectively alleviated CKD progression in two rat models, which may be related with regulation of the QPRT/NAD+/SIRT3/mitochondrial dynamics pathway.

Taurine Antioxidant Effect in Decreasing Kidney Damage in Male Mice (Mus Musculus) due to Oxidative Stress Induced by Paraquat

Paraquat toxicity occurs through the high production of reactive oxygen species (ROS) which cause damage due to oxidative stress. Antioxidants can reduce damage through prevention of oxidative stress. Taurine has shown the ability to act as an antioxidant. The aim of this research is to find a effect of antioxidant taurine to decrease kidney damage caused by oxidative stress due to paraquat by looking at the histopathology changes. 25 male adult mices from strain DDY were used and divided into five treatment groups; C(-) (Aquadest IP), C(+) (Paraquat 30mg/kg), P1 (Paraquat 30mg/kg + Taurine 250mg/kg), P2 (Paraquat 30mg/kg + Taurine 500mg/kg) and P3 (Paraquat 30mg/kg + Taurine 1000mg/kg). All groups were given treatment intraperitoneal for twenty one days. The mices were sacrificed where kidney were collected for histopathology preparation. The parameters measured were renal histopathological changes in form of degeneration and necrosis. The results show that taurine administration had an effect on decreased degrees of damage to kidney tubular cells, with a decrease in the mean degree of renal tubular degeneration and necrosis. Degeneration of renal tubular cells in groups (P2) reduced compared to the group (C+) there were significant differences (P &lt;0.05). Necrosis of renal tubular cells in groups (P1, P2) reduced compared to the group (C+) there were significant differences (P &lt;0.05). In conclusion, this research proves that administration of paraquat causes renal histopathological changes which are characterized by degeneration and necrosis. It also proves that taurine dose of 500 mg/kgBB could provided optimal effect.

Protective effect of Urtica dioica in liver and kidney damages induce by ethylene glycol in rabbits: A histopathological study

Urtica dioica is used in the many countries as seasoning and as an herbal medicine (antioxidant). In this study, adult male locale rabbit was separated into five groups, Group 1 considered as control, Group 2 to 5 animals were treated with 0.75% ethylene glycol (EG) in water to induce renal and liver damage till 30th day. The group 3 to 5 animals were feed extract of the plant of U. dioica at a dosage of 100 mg/kg body weight from day 15 to the day 30. The extracts were administered twice daily orally. Liver histopathological changes characterized by vacuolar degeneration and coagulative necrosis of hepatocytes, congestion and dilatation of central vein and sinusoids. Renal histopathological changes characterized by deposition of oxalates, blood vessels congestion infiltration of inflammatory cells and change in renal glomeruli in GE treated groups. While histopathological changes in the animals group treated with U. dioica extract and ethylene glycol showed an increase improvement of the histological features of liver tissue, were limited dilatation of renal tubules with less deposition of oxalates, as well as slight infiltration of inflammatory cells in the interstitial tissue. Finally, as a conclusion we noticed that U. dioica extracts had the ameliorative effect of ethylene glycol-induced hepatic and renal histopathological.