Kidney Tissue Samples Research Articles

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.

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.

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.

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 (5500-4200cm-1). In the mesangium, DN tissue samples exhibited higher median values at 4235cm-1, 4659cm-1, 4844cm-1, 4906cm-1, and 5222cm-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 4258cm-1, 4659cm-1, 5222cm-1, and 5346cm-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.

MiR-148b-5p regulates hypercalciuria and calcium-containing nephrolithiasis

Calcium-containing stones represent the most common form of kidney calculi, frequently linked to idiopathic hypercalciuria, though their precise pathogenesis remains elusive. This research aimed to elucidate the molecular mechanisms involved by employing urinary exosomal microRNAs as proxies for renal tissue analysis. Elevated miR-148b-5p levels were observed in exosomes derived from patients with kidney stones. Systemic administration of miR-148b-5p in rat models resulted in heightened urinary calcium excretion, whereas its inhibition reduced stone formation. RNA immunoprecipitation combined with deep sequencing identified miR-148b-5p as a suppressor of calcitonin receptor (Calcr) expression, thereby promoting urinary calcium excretion and stone formation. Mice deficient in Calcr in distal epithelial cells demonstrated elevated urinary calcium excretion and renal calcification. Mechanistically, miR-148b-5p regulated Calcr through the circRNA-83536/miR-24-3p signaling pathway. Human kidney tissue samples corroborated these results. In summary, miR-148b-5p regulates the formation of calcium-containing kidney stones via the circRNA-83536/miR-24-3p/Calcr axis, presenting a potential target for novel therapeutic interventions to prevent calcium nephrolithiasis.Graphical abstract

Silibinin-loaded Nanostructured Lipid Carriers (NLCs) Ameliorated Lead-induced Acute Nephrotoxicity in Male Rats.

As a toxic heavy metal, lead (Pb) is well known for impairment of renal function due to oxidative injuries. In contrast, the antioxidant activity of silibinin has been approved. Given the role of silibinin antioxidant activity, the present study investigated the effectiveness of silibinin-loaded nanostructured lipid carriers (Sili-NLCs) against Pb-induced acute nephrotoxicity in rats. The emulsification-solvent evaporation method was applied to prepare Sili-NLCs. Sixty male Wistar rats were divided into ten separate groups. Pb (20 mg/kg/day, i.p.) was applied to induce nephrotoxicity and in the treatment groups animals received the same concentration of silibinin and Sili-NLCs (25, 50, and 100 mg/kg/day, p.o.) for five days. After sacrificing rats, kidney tissue samples were collected to assess the oxidative stress parameters, including lipid peroxidation (LPO), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity. Also, histopathological examination using Hematoxylin-Eosin (H&E) was studied. Not only did Pb injection significantly increase the renal levels of LPO and NO, but also decreased the levels of antioxidant enzyme activity. On the other hand, Sili-NLCs were more effective than silibinin in decreasing renal oxidative damage by increasing the antioxidant defense system. Moreover, the histopathological examination correlated well with biochemical findings. Our data suggested that Sili-NLCs are potentially superior to pure silibinin for attenuating Pb-induced acute nephrotoxicity.

Unraveling the Complex Molecular Interplay and Vascular Adaptive Changes in Hypertension-Induced Kidney Disease.

Angiogenesis, the natural mechanism by which fresh blood vessels develop from preexisting ones, is altered in arterial hypertension (AH), impacting renal function. Studies have shown that hypertension-induced renal damage involves changes in capillary density (CD), indicating alterations in vascularization. We aimed to elucidate the role of the apelin receptor (APLNR), neuronal nitric oxide synthase (nNOS), and vascular endothelial growth factor (VEGF) in hypertension-induced renal damage. We used two groups of spontaneously hypertensive rats aged 6 and 12 months, representing different stages of AH, and compared them to age-matched normotensive controls. The kidney tissue samples were prepared through a well-established protocol. All data analysis was conducted with a dedicated software program. APLNR was localized in tubular epithelial cells and the endothelial cells of the glomeruli, with higher expression in older SHRs. The localization of nNOS and VEGF was similar. The expression of APLNR and nNOS increased with AH progression, while VEGF levels decreased. CD was lower in young SHRs compared to controls and decreased significantly in older SHRs in comparison to age-matched controls. Our statistical analysis revealed significant differences in molecule expression between age groups and varying correlations between the expression of the three molecules and CD.

Effect of Bee Bread (Perga) on Histopathological Changes and Immunohistochemical Expression of Apoptosis Markers in the Kidney of Rats Exposed to Cadmium

Cadmium (Cd) is an environmental and industrial pollutant that causes toxicity in various organs in humans and animals. Bee bread (perga) is a natural flavonoid with a wide range of pharmacological properties. This study was conducted to examine the effects of perga on Cd-induced nephrotoxicity. Thirty-two male Wistar rats were randomly divided into 4 groups, as the Control group, Cd group (5 mg/kg/day, orally), Perga group (0.5 g/kg/day, orally), and Cd + Perga group. At the end of the 28-day experiment, kidney tissue samples were taken and histopathological, immunohistochemical, and biochemical analyses were performed. Histopathologically, severe tubular and glomerular damage occurred as a result of Cd exposure in the Cd group. Immunohistochemically, there was an increase in caspas-3 and Bax expression in the renal tissue in the Cd group. According to the biochemical results, while the catalase, superoxide dismutase, and glutathione peroxidase antioxidant enzyme levels decreased in the Cd group, and the malondialdehyde levels increased. However, most of the above-mentioned Cd-induced changes were attenuated by treatment with perga in the Perga + Cd group. In conclusion, perga supplementation may alleviate Cd-induced renal injury through inhibition of apoptosis in renal tissue.

Enhanced kidney damage induced by increasing nonylphenol doses: impact on autophagy-related proteins and proinflammatory cytokines in rats

Nonylphenol (NP) is an organic pollutant and endocrine disruptor chemical that has harmful effects on the environment and living organisms. This study looked at whether kidney tissues subjected to increasing doses of nonylphenol generated alterations in histopathologic, pro-inflammatory, and autophagic markers. Fifty rats were divided into five groups of ten each: group I: healthy group, II: control (corn oil), group III: 25 μl/kg NP, group IV: 50 μl/kg NP, group V: 75 μl/kg NP. The kidney tissue samples were obtained for histopathological, immunohistochemical, and biochemical analyses. The histological deteriorations observed in all NP groups included tubular epithelial cell degeneration, inflammation areas, and hemorrhage. The immunohistochemical investigations showed that NP significantly elevated the autophagy markers (Beclin-1, LC3A/B, p62), pro-inflammatory cytokines (TNF-α, IL-6), HIF-1α, and eNOS in group III, IV and V compared with group I and II. The biochemical analysis also revealed that pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) increased in correlation with the NP doses, but only IL-1β reached statistical significance in NP treated rats kidney tissue. The biochemical findings have been confirmed by the histological studies. The damage to renal tissue caused by NP exposure may worsen it by increasing inflammatory and autophagic markers.

Late gestation fetal hypothyroidism alters cell cycle regulation across multiple organ systems

BackgroundHypothyroidism is a common endocrine disruption observed in utero that adversely affects fetal growth and maturation leading to long-term impacts on health; however, the exact molecular mechanisms by which these deleterious effects occur are unknown. We hypothesize that fetal hypothyroidism during late gestation will disrupt cell cycle regulation in a tissue-specific manner. To evaluate this, eight pregnant gilts were dosed with either methimazole or an equivalent negative control during days 85–106 out of 114 days of gestation (n = 4/group). Following treatment, the gilts were humanely euthanized, and tissue samples of fetal heart, ileum, kidney, lung, liver, muscle, spleen, and thymus taken from two male and two female fetuses (n = 32) from each gilt.ResultsThe relative expression of three cell cycle promoters (CDK1, CDK2, and CDK4), and one cell cycle inhibitor (CDKN1A) was compared in each tissue to determine the effect of hypothyroidism on the developing fetus. All of the eight tissues examined experienced at least one significant up- or downregulation in the expression of the aforementioned genes as a result of treatment with methimazole. Substantial changes were observed in the liver and muscle, with the latter experiencing significant downregulations of CDK1, CDK2, and CDK4 as a result of treatment. In addition, all tissues were examined for changes in protein content, which further elucidated the impact of hypothyroidism on the fetal liver by the observation of a marked increase in protein content in the methimazole-treated group. Finally, the heart and liver were histologically examined for evidence of cellular hyperplasia and hypertrophy by measuring average nuclei density and size in each tissue, with the results showing a significant decrease in average nuclei size in the liver of hypothyroid fetuses.ConclusionsCollectively, these findings indicate the occurrence of organ-specific disruptions in cell cycle progression as a result of in utero hypothyroidism, which may explain the long term and widespread effects of hypothyroidism on fetal development.