Kidney Tissue Samples Research Articles

Naringin Affects Caspase-3, IL-1β, and HIF-1α Levels in Experimental Kidney Ischemia-Reperfusion in Rats.

Microvascular dysfunction develops in tissues after Ischemia-Reperfusion (IR). The current study aimed to determine the effect of naringin supplementation on kidney caspase-3, IL-1β, and HIF-1α levels and kidney histology in rats undergoing unilateral nephrectomy and kidney-ischemia reperfusion. The study was conducted on 8-12 weeks old 40 Wistar-type male rats. Experimental renal ischemia- reperfusion and unilateral nephrectomy were performed under general anesthesia in rats. Experimental groups were formed as follows: 1-Control group, 2-Sham control + Vehicle group, 3- Renal ischemia-reperfusion (Renal I+R) + Vehicle group, 4-Renal I+R + Naringin (50 mg/kg/day) group (3 days application) group, 5-Renal I+R + Naringin (100 mg/kg/day) group (3 days supplementation). Nephrectomy in the left kidneys and the ischemia for 45 minutes and reperfusion in the right kidneys followed by 72 hours of reperfusion. Naringin was administered intraperitoneally at the beginning of the reperfusion, 24 hours and 48 hours later. At the end of the experiments, blood was first taken from the heart in animals under general anesthesia. Then, the animals were killed by cervical dislocation, and kidney tissue samples were taken. Tissues were evaluated for caspase-3, IL-1β, and HIF-1α as well as histologically. As a result of ischemia in kidney tissues, HIF-1α decreased, while caspase-3 and IL-1β increased. IR also caused damage to the kidney tissue. However, naringin supplementation corrected the deterioration to a certain extent. The results of the study showed that naringin may have protective effects on kidney damage due to anti-inflammatory and antiapoptosis mechanisms caused by unilateral nephrectomy and IR in rats.

Short-term Administration of Naringin Improves Renal Function in Renal Ischemia-reperfusion by Increasing Aquaporin-1 and Aquaporin-2 Levels

Background: Since renal ischemia-reperfusion (I/R) can lead to a serious health problem, aquaporins have important roles in preventing negative changes in electrolyte-water balance. This study aimed to determine the effect of naringin treatment on renal function and AQP1 and AQP2 levels in the kidney cortex and medulla tissues in experimental renal I/R in rats. Materials and Methods: The study was carried out on 40 male Wistar-type rats, 8-12 weeks old. Experimental groups were formed as follows: 1) Control, 2) Sham+vehicle, 3) Renal (I/R)+vehicle, 4) Renal I/R+ Naringin (50mg/kg/day) (3 days of administration), and 5) Renal I/R+ Naringin( 100mg/kg/day) (3 days supplementation) group. First, the left kidney was removed by nephrectomy under general anesthesia, and then the right kidney was subjected to 45 minutes of ischemia and then 72 hours of reperfusion. Naringin was given to the experimental animals by an intraperitoneal route at the beginning of the reperfusion, after 24 and 48 hours. At the end of the experiments, first of all, blood samples were taken from the heart in animals under general anesthesia, and then the animals were killed by cervical dislocation, and kidney tissue samples were taken. Osmolarity in plasma and urine and plasma creatinine levels were evaluated. AQP1 and AQP2 levels were analyzed in the kidney cortex and medulla tissues by ELISA and PCR methods. Results: In kidney tissues, I/R led to a decrease in plasma and urinary osmolality, AQP1 and AQP2 levels in the cortex and medulla, and an increase in urea and creatinine levels (p < 0.001). However, naringin supplementation corrected the deterioration to a certain extent. Conclusion: The results of the study show that naringin supplementation at different doses, such as 50 or 100 mg/kg, may have protective effects on the deterioration of renal function caused by unilateral nephrectomy and I/R in rats.

Isolation and Molecular Characterization of Pathogenic Leptospira spp. from Brown Rats (Rattus norvegicus) in Zaria and Environs, Kaduna, Nigeria, 2022.

Leptospirosis caused by the pathogenic serovars of Leptospira spp. is a zoonotic disease of global importance. Brown rats (Rattus norvegicus), due to their worldwide distribution and reservoir host status, are considered the most important reservoir for environmental leptospiral persistence and infections in animals. We aimed to isolate, identify, and characterize Leptospira spp. circulating among brown rat populations in Zaria, Kaduna state, Nigeria. Kidney samples from 305 brown rats from different locations in Zaria were collected April-June 2022 and cultured using bacteriologic methods. We also extracted DNA from 24 kidney tissue samples for molecular detection of pathogenic Leptospira spp. and for phylogenetic analysis. Leptospira spp. was detected in 57.7% of the samples by using culture methods and in 91.7% of the samples by using PCR. The phylogenetic tree revealed two distinct clusters among the reference sequences, aligning with the known P1 and P2 subclades. The sequences from this study all clustered together on the phylogenetic tree and were most similar to Leptospira interrogans serovar Pomona strain RZ 11. The high prevalence of Leptospira spp. detected in Zaria suggests that further surveillance and assessment of the public risk are warranted.

Pathological effects and immune modulation in host during Tilapia Parvovirus (TiPV) outbreak in cage and wetland Tilapia farms.

Viral diseases arising in farmed fish are an ongoing challenge to the aquaculture industry, causing severe mortality and economic losses. Recently, there has been a spike in the incidence of a viral disease caused by Tilapia Parvovirus (TiPV) inflicts irreparable damage, and large-scale fish kills in the farmed tilapia species. We investigated a case of disease outbreak and severe mortality in cage and wetland farms of tilapia in West Bengal and Odisha, India. The symptomatic fish showed clinical signs, including hemorrhage, discoloration, ulcer, and redness in the body surfaces. Further analysis revealed that Tilapia Parvovirus was associated (validated by PCR, phylogenetic analysis, and cell line assay) with the infection and mortality of tilapia. The virus was detected in gill, heart, spleen, liver, and kidney samples collected from apparently healthy (asymptomatic) and symptomatic tilapia samples from cage and wetland farms. At the same time, negative results were found in the brain and skin tissue samples. The histological analysis revealed that TiPV induces severe damage invariably in almost all studied tissue, including the liver, kidney, spleen, gill, heart, and brain of tilapia samples. The viral quantification analysis showed that the viral genome was higher in the liver, spleen, and heart than in the tilapia samples' gill, kidney, or brain tissue. Furthermore, the study indicated that TiPV infection has a significant effect on the health of tilapia. The tilapia exhibited an immune reactivity toward TiPV infection (upregulation of chemokine receptors, CRs and interleukin 1β, IL-1β), the majority of the studied immune genes (interleukin 8, IL-8; Toll-like receptors 7, TLR7; tumour necrosis factor α, TNF-α; major histocompatibility complex II, MHC II and nuclear factor kappa B, NF-kB) were significantly downregulated in the kidney, spleen and liver tissue samples of symptomatic tilapia. Further, the in vivo challenge assay confirms that the isolated TiPV is a novel parvovirus pathogen that causes massive mortality in tilapia. The lessons learned from the first cellular and molecular description associated with TiPV epidemiology from wetland and cage farms of tilapia could be critical to developing the current state of the tilapia farming industry. Additionally, a holistic approach is needed to develop management measures to control the virulence and risk factors of TiPV.

Lumbrokinase (LK) ameliorates diabetic kidney disease renal fibrosis through regulating snail via m6A RNA methyltransferase 3

The present study was undertaken to investigate the therapeutic effect and underlying mechanisms of lumbrokinase (LK) on diabetic kidney disease (DKD). Kidney tissue samples from DKD patients and normal controls were collected from hospitals. The type 2 diabetic nephropathy model was induced in db/db mice. The mice were then randomly divided into a model group (DM group) and an LK group. db/m mice were used as the control group (Con group). After 12 weeks of treatment with LK (234 KU/kg/day), biochemical parameters were tested, and pathological changes in the kidney were observed under a light microscope. The epithelial-to-mesenchymal transition (EMT), mRNA m6A methylation proteins, and activated TGF-β1/Smad pathway components were assessed by western blot or immunofluorescence in DKD patients, model mice, and high glucose-stimulated HK-2 cells. We found that the m6A eraser METTL3 was expressed at low levels in DKD patients, model mice, and high glucose-stimulated HK-2 cells. METTL3 overexpression reversed the high glucose-induced activation of the TGF-β1/Smad pathway and EMT through snail in vitro. However, LK can restore the expression of the m6A-modifying enzyme METTL3 in vivo and in vitro, suppressed EMT, and alleviated renal interstitial fibrosis by downregulating snail. Overall, LK ameliorated renal fibrosis through the regulation of Snail via m6A RNA METTL3.

Toxicological Evaluation of Sargassum polycystum in Mice with Loperamide-Induced Constipation

Constipation gradually increases in people after the age of 50 years leading to difficulty in stool passage. Until now, there have been no effective drugs without side effects. This study investigated the preventive potential and toxicity of Sargassum polycystum extract (SPE) against loperamide-induced constipation in mice. Daily oral administration of SPE (100, 500 and 1000 mg/kg) for 14 days significantly increased defecation frequency in constipation mice. Additionally, no significant differences in blood haematological and biochemical indices between the control, constipation and SPE-treated groups were detected. Histopathological examinations revealed non-toxic effects in liver, kidney and colon tissue samples from the SPE-treated groups compared with the control and constipation groups. Real-time polymerase chain reaction showed that the administration of SPE significantly modulated Saa3, Odc1 and Clu expressions that promote the health of living organisms compared with the control group. Overall, this study showed that daily oral administration of Sargassum polycystumfor 14 days could prevent constipation without any adverse effects. Sargassum polycystumis suitable for further use as a supplement or drug to manage constipation.

The emergence of multidrug-resistant Proteus vulgaris infection in cage reared Pangasianodon hypophthalmus: Molecular characterization and host-pathogen response

The study investigates the causative agent responsible for massive mortality in Pangasianodon hypophthalmus cage farms. The infected pangasius were lethargic, not taking feed, and had exophthalmia, deep ulceration, and hemorrhage on the ventral body surface. Pathogens were isolated from infected pangasius tissue samples, and the strain was preliminarily identified as Proteus vulgaris based on morphology, biochemical tests, 16S rRNA PCR sequencing, and phylogenetic analysis. The microbiological analysis revealed that P. vulgaris was associated with the disease outbreak and mortality of P. hypophthalmus, as confirmed by the biofilm formation, swimming activity, and survival assay results. The isolated P. vulgaris was resistant to several antibiotics, including Doxycycline, Dicloxacillin, Polymyxin B, Chloramphenicol, and Imipenem, exhibiting multiple antibiotic-resistant phenotypes. Furthermore, a host-pathogen model was developed to investigate the in vivo effect of emerging P. vulgaris infection in striped catfish. Results showed that P. vulgaris infection exhibited varying degrees of cellular changes in the kidney, liver, and gill tissues of infected P. hypophthalmus samples. The transcription analysis further highlights that P. vulgaris modulates the antioxidants, immune activation, growth regulator, homeostasis, degradation of invading DNA, and DNA damage-related gene expression in liver, kidney, spleen, skin, and gill tissue samples of infected P. hypophthalmus. The lessons learned from the study could be critical in understanding the P. vulgaris infection patterns and pathobiology necessary to enable risk assessment and develop management measures to control the bacterium's virulence.

S100A2 activation promotes interstitial fibrosis in kidneys by FoxO1-mediated epithelial-mesenchymal transition

BackgroundRenal interstitial fibrosis (RIF) is a common feature of chronic kidney diseases (CKD), with epithelial-mesenchymal transition (EMT) being one of its important mechanisms. S100A2 is a protein associated with cell proliferation and differentiation, but its specific functions and molecular mechanisms in RIF remain to be determined.MethodsS100A2 levels were evaluated in three mouse models, including unilateral ureteral obstruction (UUO), ischemia-reperfusion injury (IRI), and aristolochic acid nephropathy (AAN), as well as in TGF-β1- treated HK-2 cells and in kidney tissue samples. Furthermore, the role of S100A2 and its interaction with FoxO1 was investigated using RT-qPCR, immunoblotting, immunofluorescence staining, co-immunoprecipitation (Co-IP), transcriptome sequencing, and gain- or loss-of-function approaches in vitro.ResultsElevated expression levels of S100A2 were observed in three mouse models and TGF-β1-treated HK2 cells, as well as in kidney tissue samples. Following siRNA silencing of S100A2, exposure to TGF-β1 in cultured HK-2 cells suppressed EMT process and extracellular matrix (ECM) accumulation. Conversely, Overexpression of S100A2 induced EMT and ECM deposition. Notably, we identified that S100A2-mediated EMT depends on FoxO1. Immunofluorescence staining indicated that S100A2 and FoxO1 colocalized in the nucleus and cytoplasm, and their interaction was verified in Co-IP assay. S100A2 knockdown decreased TGF-β1-induced phosphorylation of FoxO1 and increased its protein expression, whereas S100A2 overexpression hampered FoxO1 activation. Furthermore, pharmacological blockade of FoxO1 rescued the induction of TGF-β1 on EMT and ECM deposition in S100A2 siRNA-treated cells.ConclusionS100A2 activation exacerbates interstitial fibrosis in kidneys by facilitating FoxO1-mediated EMT.Graphical abstractA schematic diagram of the underlying mechanisms by which S100A2 regulates EMT and renal fibrosis. Following injury, the cytoplasmic expression of S100A2 in renal tubular epithelial cells is markedly elevated. This increase promotes the phosphorylation of FoxO1, preventing its translocation into the nucleus and enhances EMT and extracellular matrix ECM deposition, thereby exacerbating renal interstitial fibrosis.

SMYD2 Promotes Calcium Oxalate-Induced Glycolysis in Renal Tubular Epithelial Cells via PTEN Methylation.

Background/Objectives: Damage to renal tubular cells (RTCs) represents a critical pathological manifestation in calcium oxalate (CaOx) stone disease, but the underlying mechanism remains elusive. Energy metabolism reprogramming is a vital influencer of RTC survival, and SMYD2 is a histone methylation transferase that has been extensively implicated in various metabolic disorders. Hence, this research aimed to identify whether SMYD2 induces the reprogramming of energy metabolism in RTCs exposed to CaOx nephrolithiasis. Methods: Kidney samples were obtained from patients who underwent laparoscopic nephrectomy for non-functioning kidneys caused by nephrolithiasis. The glyoxylate-induced CaOx stone mice model was established and treated with AZ505. The SMYD2-knockout HK-2 cell line was constructed. Histological changes were evaluated by HE, VK, Tunel, Masson stainings. The molecular mechanism was explored through co-immunoprecipitation and western blotting. Results: The results found that SMYD2 upregulation led to energy reprogramming to glycolysis in human kidney tissue samples and in mice with CaOx nephrolithiasis. We also identified the substantial involvement of glycolysis in the induction of apoptosis, inflammation, and epithelial-mesenchymal transition (EMT) in HK-2 cells caused by calcium oxalate monohydrate (COM). In vivo and in vitro results demonstrated that SMYD2 inhibition reduces glycolysis, kidney injury, and fibrosis. Mechanistically, SMYD2 was found to promote metabolic reprogramming of RTCs toward glycolysis by activating the AKT/mTOR pathway via methylated PTEN, which mediates CaOx-induced renal injury and fibrosis. Conclusions: Our findings reveal an epigenetic regulatory role of SMYD2 in metabolic reprogramming in CaOx nephrolithiasis and associated kidney injury, suggesting that targeting SMYD2 and glycolysis may represent a potential therapeutic strategy for CaOx-induced kidney injury and fibrosis.

The Effect of Chrysin-nanocrystal on Oxidative Stress Indices and Histopathological changes in Kidney Tissue of Rats Exposed to Chlorpyrifos

Aims: The current study looked at the effect of nanocrystal chrysin on the effects of chlorpyrifos on kidney function, as well as the histopathological changes in this tissue and its potential as an antioxidant in the kidneys of adult male rats. Background: The effect of nanocrystal chrysin on the kidneys of rats exposed to chlorpyrifos has not been fully understood. Objective: The safety and efficacy of nanocrystal chrysin was evaluated. Methods: The rats were randomly divided into six groups of six rats each: 1) a control group treated with corn oil, 2) a group treated with chrysin nanocrystals (5 mg/kg), 3) a group treated with chrysin nanocrystals (10 mg/kg), 4) a group treated with chrysin nanocrystals (5 mg/kg) + chlorpyrifos (30 mg/kg), 5) a group treated with chrysin nanocrystals (10mg/kg) + chlorpyrifos (30 mg/kg). After the intervention, serum and kidney tissue samples were separated. Results: Histology and biochemical factors at the serum level did not reveal any significant changes in all treated groups versus the control group. Additionally, the morphology of the renal tubules in all groups, including the glomeruli, was normal. There was no inflammation, congestion, necrosis, or degeneration. Conclusion: In this study, the serum levels of urea, creatinine, bilirubin, and albumin, which are indicators of kidney function, as well as oxidative stress indices and kidney morphology in animals given doses of 5 mg/kg and 10 mg/kg of chrysin nanocrystals did not change. This study suggests that chrysin nanocrystals with an average diameter of 155 nm may be a safe and efficient antioxidant.

Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach

Chronic kidney disease (CKD) progression involves tubulointerstitial fibrosis, a process characterized by excessive extracellular matrix accumulation. To identify potential biomarkers for kidney fibrosis, we performed mass spectrometry-based proteomic profiling of human kidney tubular epithelial cells and kidney tissue from a 5/6 nephrectomy rat model. Multidisciplinary analysis across kidney fibrosis models revealed 351 differentially expressed proteins associated with kidney fibrosis, and they were enriched in processes related to the extracellular matrix, kidney aging, and mitochondrial functions. Network analysis of the selected proteins revealed five crucial proteins, of which transgelin emerged as a candidate protein that interacts with known fibrosis-related proteins. Concordantly, the gene expression of transgelin in the kidney tissue from the 5/6 nephrectomy model was elevated. Transgelin expression in kidney tissue gradually increased from intermediate to advanced fibrosis stages in 5/6 Nx rats and mice with unilateral ureteral obstruction. Subsequent validation in kidney tissue and urine samples from patients with CKD confirmed the upregulation of transgelin, particularly under advanced disease stages. Moreover, we investigated whether blocking TAGLN ameliorated kidney fibrosis and reduced reactive oxygen species levels in cellular models. In conclusion, our proteomic approach identified TAGLN as a potential noninvasive biomarker and therapeutic target for CKD-associated kidney fibrosis, suggesting its role in modulating mitochondrial dysfunction and oxidative stress responses.

Near-infrared microscopy reveals diabetic nephropathy in ob/ob mice

Diabetic nephropathy (DN) is a major cause of global kidney failure. While histological kidney biopsy is the gold standard for diagnosis, it primarily reveals tissue morphology. In contrast, near-infrared (NIR) microscopy offers a label-free method for detailed molecular characterization of kidney tissue. Hematoxylin and eosin-stained kidney tissue samples from 17 ob/ob mice with DN and 14 healthy mice were examined using Fourier transform-NIR microscopy. Four different spectra were obtained from both the mesangium and tubulus. NIR spectral analysis unveiled distinct differences in wavenumbers between DN-affected and healthy kidneys, notably in the carbohydrate and protein-associated region (5500-4200 cm−1). In the mesangium, DN tissue samples exhibited higher median values at 4235 cm−1, 4659 cm−1, 4844 cm−1, 4906 cm−1, and 5222 cm−1 compared to controls (P < 0.05, P < 0.01, P < 0.05, P < 0.05 and P < 0.001, respectively). In tubular spectra, higher median values were found at 4258 cm−1, 4659 cm−1, 5222 cm−1, and 5346 cm−1 in the DN group (P < 0.01, P < 0.05, P < 0.05 and P < 0.01, respectively). These spectral differences strongly correlated with metabolic, histologic, and urinary parameters, providing valuable DN progression insights. The classification model achieved a visible clustering between the control and DN group for both the mesangial and tubular measurements. NIR microscopy demonstrated significant spectral differences between DN and healthy kidney tissues in mice, hinting at its potential for providing chemical insights, aiding in more accurate diagnoses, and offering a foundation for further clinical exploration and potential therapeutic advancements in DN.

The Novel Nephroprotective Activity of Flaxseed Oil on Diazinon-induced Kidney Damage in Male Rats.

In male rats, the flaxseed oil (FS-oil) modulatory properties were investigated on diazinon (DZN)-induced nephrotoxicity. Adult male Wistar rats were divided randomly into five groups. To induce nephrotoxicity, animals received DZN (70 mg/kg/day, p.o.). Also, treatment groups received FS-oil (100 and 200 mg/kg/day, p.o.). The animal treatment was 28 consecutive days. On the 29th day, serum and kidney tissue samples were removed and serum levels of the creatinine, blood urea nitrogen (BUN), malondialdehyde (MDA), glutathione peroxidase (GPx), and catalase (CAT), were measured. Also, hematoxylin and eosin (H&E) staining was applied for histological studies. DZN significantly increased the BUN, creatinine, and MDA levels compared to the control group. Besides, DZN significantly decreased the GPx and CAT activity in the kidney tissue. However, the modulatory effects of FS-oil were observed by improving renal enzyme factors, inhibiting oxidative stress, and histological change. This study demonstrated that FS-oil ameliorated DZN-induced nephrotoxicity and can be used as a preventive agent against DZN toxicity because of the FS-oil antioxidant characteristics.

COVID-19-Induced Changes in the Fibrin Network of Pulmonary and Renal Microthrombi

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often causes coagulation disorders that affect highly vascularized organs, such as the lungs and kidneys. Objective The objective of this study was to report the histopathological findings of variations in the fibrin pattern of pulmonary and renal microthrombi in patients who died from SARS-CoV-2 infection. Methods Minimally invasive autopsies were performed on 40 patients to collect lung (n=40) and kidney (n=16) tissue samples. Histochemical and immunohistochemical staining techniques were used for histopathological analyses. Premortem laboratory data were obtained from the patients' electronic medical records. Results The lung tissue showed a patchy pattern, characterized by areas of both minimal and severe damage. The most significant histopathological finding was the detection of thrombi with fibrin structures organized into discrete star-shaped units, which were more frequently observed in areas with severe lung injury than in those with minimal lung injury (p = 0.012). Star-shaped fibrin structures were also observed in the renal glomerular capillaries. Immunohistochemical staining revealed the presence of platelets and the procoagulant proteins von Willebrand factor (VWF) and Factor VIII within the star-shaped fibrin thrombi. Patients with star-shaped fibrin thrombi had higher levels of the systemic inflammatory indicators C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR). Conclusion Our observations suggest that the inflammatory microenvironment resulting from SARS-CoV-2 infection may contribute to the formation of star-shaped fibrin units in the pulmonary and renal microthrombi.

Therapeutic Effect of Thymoquinone on Melatonin, Ferritin, and Renal Function in Renal Ischemia/Reperfusion Injury in Rats

Objective: Ischemia/reperfusion (I/R) injury is the period of tissue or organ damage that develops after the tissue's blood flow is restored. The extent of damage varies according to the severity of tissue and cell damage. Thymoquinone (TQ) has a wide therapeutic spectrum. The effect of thymoquinone on melatonin and ferritin in I/R can regulate renal function by combining these two mechanisms to improve damage. Therefore, the effect of thymoquinone on melatonin and ferritin levels in renal I/R as well as its regulatory role in renal functions have been investigated. Methods: Thirty-six male Sprague Dawley rats were included in the study (250-300 g, 8-10 weeks). The rats were randomly assigned to 6 groups with 6 animals in each group. Groups; 1- Control, 2- Sham, 3- Solvent, 4- Renal ischemia/reperfusion injury (I/R), 5- I/R+ Thymoquinone (TQ) (5 mg/kg/day), 6- TQ (5 mg/kg/day). The dorsal region of the rats was surgically opened, and the left renal artery was clamped for 30 minutes and then reperfused for 24 hours. TQ (i.p) was applied to the treatment groups for 15 days. At the end of the experiment, blood samples were taken from all groups, and kidney function tests (Na+, K+, Creatinine, urea, BUN) were performed. Melatonin and ferritin levels were analyzed by the ELISA method from kidney tissue samples. Results: Data showed that short-term TQ treatment was effective on serum K+ (P = 0.010) and melatonin and ferritin levels in kidney tissue. Melatonin and iron activity, which were normal in healthy groups, melatonin decreased and ferritin increased significantly in the I/R group. TQ treatment positively regulated the dysregulation of these two molecules in I/R. Conclusion: TQ may contribute to the healing of the damage by improving the K+ levels, which indicates the insufficiency of kidney functions in I/R damage. Melatonin and ferritin, as interacting molecules in I/R, are regulated by TQ, indicating that they may contribute to the management of I/R damage.

Prevention of Transition from Acute Kidney Injury to Chronic Kidney Disease Using Clinical-Grade Perinatal Stem Cells in Non-Clinical Study.

Acute kidney injury (AKI) is widely recognized as a precursor to the onset or rapid progression of chronic kidney disease (CKD). However, there is currently no effective treatment available for AKI, underscoring the urgent need for the development of new strategies to improve kidney function. Human placental mesenchymal stromal cells (hpMSCs) were isolated from donor placentas, cultured, and characterized with regard to yield, viability, flow cytometry, and potency. To mimic AKI and its progression to CKD in a rat model, a dedicated sensitive non-clinical bilateral kidney ischemia-reperfusion injury (IRI) model was utilized. The experimental group received 3 × 105 hpMSCs into each kidney, while the control group received IRI and saline and the untreated group received IRI only. Urine, serum, and kidney tissue samples were collected over a period of 28 days. The hpMSCs exhibited consistent yields, viability, and expression of mesenchymal lineage markers, and were also shown to suppress T cell proliferation in a dose-dependent manner. To ensure optimal donor selection, manufacturing optimization, and rigorous quality control, the rigorous Good Manufacturing Practice (GMP) conditions were utilized. The results indicated that hpMSCs increased rat survival rates and improved kidney function by decreasing serum creatinine, urea, potassium, and fractionated potassium levels. Furthermore, the study demonstrated that hpMSCs can prevent the initial stages of kidney structural fibrosis and improve kidney function in the early stages by mitigating late interstitial fibrosis and tubular atrophy. Additionally, a robust manufacturing process with consistent technical parameters was established.

Pathogenesis of Experimental Infection of Nile Tilapia (Oreochromis niloticus) with Nucleospora Braziliensis Pathology and Proteomic of Microsporidia.

The recent discovery of disease caused by Nucleospora braziliensis in Nile tilapia (Oreochromis niloticus) is important as it has highlighted the high prevalence of infection and associated mortality in cultured fish. Thus, this study conducted an experimental infection of this microsporidium to evaluate pathological alterations and conduct proteomic analysis. For pathological observation, samples of brain, eyes, gall bladder, gut, heart, kidney, liver, muscle, skin, spleen, and stomach tissue, were collected, and liquid chromatography-mass spectrometry (LC-MS/MS) was performed for proteomic analysis. The most prevalent lesions were brownish color of the liver, gill filament fusion, gut ischemia, hemorrhage of the lips and fins, hepatomegaly, spleen atrophy, splenomegaly, and stomach congestion. The most common microscopic lesions were degeneration, hemorrhage, and inflammation in the brain, gills, gut, kidney, liver, muscle, spleen, and stomach. The digested peptides were identified by LC-MS/MS and the intersection of each group showed that in the spleen there were 121 exclusive proteins in the infected sample and 252 in the control, while in the kidney, 129 proteins were identified in the infected specimen compared to 83 in the control. In conclusion, this study demonstrates the proteome profile of O. niloticus kidney and spleen tissue in response to infection with N. braziliensis.

The KDR Gene rs2071559 and the VEGF Gene rs6921438 May Be Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus.

The aim of our study was to investigate an association between polymorphisms of either the VEGF (vascular endothelial growth factor) gene (rs6921438) or the KDR (kinase insert domain receptor) gene (rs2071559, rs2305948) and DN (diabetic nephropathy) in Caucasians with T2DM (type 2 diabetes mellitus). The second aim was to investigate the effect of either the VEGF gene (rs6921438) or the KDR gene (rs2071559, rs2305948) on the immune expression of either VEGF or KDR in the renal tissues of T2DM subjects (to test the functional significance of tested polymorphisms). The study included 897 Caucasians with T2DM for at least ten years (344 patients with DN and 553 patients without DN). Each subject was genotyped and analyzed for KDR (rs1617640, rs2305948) and VEGF (rs6921438) polymorphisms. Kidney tissue samples taken from 15 subjects with T2DM (autopsy material) were immunohistochemically stained for the expression of VEGF and KDR. We found that the rs2071559 KDR gene was associated with an increased risk of DN. In addition, the GG genotype of the rs6921438 VEGF gene had a protective effect. We found a significantly higher numerical area density of VEGF-positive cells in T2DM subjects with the A allele of the rs6921438-VEGF compared to the homozygotes for wild type G allele (7.0 ± 2.4/0.1 mm2 vs. 1.24 ± 0.5/0.1 mm2, respectively; p < 0.001). Moreover, a significantly higher numerical area density of KDR-positive cells was found in T2DM subjects with the C allele of rs2071559 (CC + CT genotypes) compared to the homozygotes for wild type T allele (9.7± 3.2/0.1 mm2 vs. 1.14 ± 0.5/0.1 mm2, respectively; p < 0.001) To conclude, our study showed that the presence of the C allele of the rs2071559 KDR gene was associated with a higher risk of DN, while the G allele of the rs6921438-VEGF conferred protection against DN in Slovenian T2DM subjects.

Carvacrol attenuates amikacin-induced nephrotoxicity in the rats

Objective: Amikacin (AK) is a wide-spectrum antibiotic routinely used to treat gram-negative and some gram-positive bacterial infections. However, its use is limited due to its potential to cause nephrotoxicity due to an increase in reactive oxygen radicals. The main goal of this study was to investigate the effect of carvacrol (CAR) on AK-induced nephrotoxicity in rats. Methods: Thirty-two Sprague Dawley rats were randomly separated into four groups: the control (0.9% NaCl solution and sunflower oil), AK (400 mg/kg), CAR+AK (80 mg/kg CAR+400 mg/kg AK), and AK+CAR (400 mg/kg AK+80 mg/kg CAR) groups. AK and CAR were administered intramuscularly and orally, respectively for 7 days. Blood and kidney tissue samples were collected at the end of the experiment. The level of catalase, superoxide dismutase, malondialdehyde, and reduced glutathione, which are parameters of oxidative stress, were detected while comparing renal function and histopathological changes. Results: Histopathological findings (necrotic changes, dilatation and inflammatory cell infiltration) were significantly greater in the AK group than in the control group. Additionally, significant weight loss was detected in the rats in the AK group. CAR treatment, both before and after AK administration, significantly improved nephrotoxicity histopathologically (p&amp;lt;.05). However, the same improvement was not identified biochemically. Conclusion: CAR treatment significantly improved nephrotoxicity both before and after AK administration, suggesting that carvacrol has a protective effect against AK-induced kidney damage at the histopathological level. Keywords: Antioxidant, amikacin, carvacrol, nephrotoxicity, oxidative stress, rat

Linalool may have a therapeutic effect on cadmium-induced nephrotoxicity by regulating NF-κB/TNF and GRP78/CHOP signaling pathways

Cadmium (Cd) is an environmental pollutant heavy metal with nephrotoxic effect. One of the primary constituents of essential oils is Linalool (Lin), a monoterpene having a variety of pharmacological properties including antimicrobial, anti-inflammatory, and antioxidant effects. The purpose of this study was to ascertain how Lin affected endoplasmic reticulum stress (ERS) and pro-inflammatory mediators in Cd-induced nephrotoxicity. In the experiment, 28 male rats were randomly divided into four equal groups as control (no application), Cd (Cd at a dose of 3 mg/kg for the first 7 days), Cd+Lin (Cd at a dose of 3 mg/kg for the first 7 days and 100 mg/kg/day Lin) and Lin (100 mg/kg/day Lin) (n=7). The experiment was completed on the 15th day after all treatments were performed. Blood serum and kidney tissue samples were used for analyses. Cd-induced histopathological changes, inflammation, oxidative stress, and apoptosis were determined to increase in kidney tissue. However, it was observed that Cd-induced adverse effects in kidney tissue were mainly eliminated by Lin treatment. In conclusion, Lin demonstrated anti-inflammatory, anti-oxidant and anti-apoptotic effects in Cd-induced nephrotoxicity. Therefore, we believe that Lin may represent a high potential therapeutic strategy against renal tissue damage.