Necrosis Of Epithelial Cells Research Articles

Inhibition of cytochrome P450 2E1 and activation of transcription factor Nrf2 are renoprotective in myoglobinuric acute kidney injury

Rhabdomyolysis accounts for ∼10% of acute kidney injuries. In glycerol-induced myoglobinuric acute kidney injury, we found an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear protein, a key redox-sensitive transcription factor, and Nrf2-regulated genes and proteins including upregulation of heme oxygenase-1. In in vitro studies, pretreatment of LLC-PK1 cells with an activator of Nrf2 before myoglobin exposure significantly decreased oxidant generation and cytotoxicity, whereas Nrf2 inhibition and gene silencing exacerbated the injury. Chlormethiazole, a specific CYP2E1 transcription inhibitor, prevented an increase in catalytic iron in the kidneys, decreased oxidative stress, blocked nuclear translocation of the Nrf2 protein, decreased heme oxygenase-1 upregulation, and provided functional and histological protection against acute kidney injury. CYP2E1 inhibitors and gene silencing in renal tubular epithelial cells significantly decreased reactive oxygen species generation and provided marked protection against myoglobin-induced cytotoxicity. Thus, during CYP2E1-induced oxidative stress, the transcription factor Nrf2 has a pivotal role in the early adaptive response. Inhibition of CYP2E1 coupled with the prior induction of Nrf2 may be a valuable tool to reduce CYP2E1-mediated rhabdomyolysis-induced acute kidney injury.

The loss of αSNAP downregulates the expression of occludin in the intestinal epithelial cell of acute pancreatitis model

Background and objectiveIntestinal barrier damage is an important event during the occurrence and progression of severe acute pancreatitis. The expression of occludin, one of the main components of the intestinal barrier proteins, is regulated by various factors related to intestinal barrier formation and the remodeling process. The αSNAP, as a novel membrane protein, is ubiquitously expressed in intestinal epithelial cells. This study aimed to investigate the role of αSNAP in acute pancreatitis and the relationship between occludin and αSNAP. MethodsMild and severe acute pancreatitis models were established by retrograde injections of 0.5% and 3.8% sodium taurocholate solutions, respectively, into rat pancreaticobiliary ducts. The animals were killed at 1, 2, and 3 days after the injection, and the pathological changes of the pancreas and intestinal mucosa, the changes in intestinal permeability, and the protein expression of occludin and αSNAP were assessed. Cultured epithelial IEC-6 cells were further infected with lentiviral αSNAP shRNA, cell apoptosis was determined with flow cytometry (FCM), and any changes in occludin expression were detected by Western blotting and immunofluorescent staining. ResultsThis pathologic study of a rat acute pancreatitis model indicated pancreatic tissue necrosis and inflammatory cell infiltration; the intestinal villi in the severe acute pancreatitis (SAP) group demonstrated edema, lodging, atrophy, and intestinal epithelial cell necrosis, and shedding. The intestinal permeability in rats with pancreatitis increased significantly. The SAP group showed significantly increased levels of serum TNF-α and endotoxins. The results of immunofluorescent staining and Western blotting revealed that compared with the SO (sham operation) and MAP (mild acute pancreatitis) groups, the SAP group displayed significantly downregulated protein expressions of αSNAP and occludin in the intestinal epithelial cells. After the lentiviral transduction of αSNAP shRNA, apoptosis in IEC-6 cells was drastically increased, whereas the expression of occludin was decreased significantly. ConclusionThe downregulated expression of αSNAP in intestinal epithelial cells leads to reduced occludin expression and enhanced apoptosis of intestinal epithelial cells. Hence, the permeability of the intestinal barrier may be increased in a severe acute pancreatitis model.

Outbreak of a novel disease associated with Vibrio mimicus infection in fresh water cultured yellow catfish, Pelteobagrus fulvidraco

An outbreak of a novel disease characterized by serious and regularly shaped ulcers in the skin was recorded in cultured yellow catfish (Pelteobagrus fulyidraco) in Guangdong and Guangxi provinces of South-China in 2011. Several bacterial strains that exhibited the same phenotypic traits and biochemical characteristics were isolated from the lesions of diseased fish. One bacterial isolate named XQ was identified as Vibrio mimicus according to biochemical tests and phylogenetic analysis derived from 16S rDNA, rpoA, recA and pyrH gene sequencing. In challenge trials, the bacterial isolate XQ exhibited high virulence in yellow catfish with an intra-peritoneal LD50 value of 3.39 x 10(6) CFU per fish. In addition, skin ulcers occurred in all challenged fish groups whether they were treated with the bacterial isolate XQ by intraperitoneal injection, oral delivery or bath exposure, suggesting that the V. mimicus is the etiological agent of the enzootic and could infect the host fish via more than one route. Furthermore, histopathology of diseased fish infected with V. mimicus showed destruction of the epidermis and fibrinoid necrosis in skin; renal tubular epithelial cell necrosis in kidney; hepatocyte swelling and serious hemorrhage in the liver; macrophage aggregations and necrosis of the lymphoid tissue in spleen; severe necrosis and shedding of the intestinal mucosal villi in intestines; and, edema and exfoliation of epithelial cells in gill secondary lamellae. (C) 2014 Elsevier B.V. All rights reserved.

Fibrose cardíaca associada à intoxicação por Amorimia septentrionalis em bovinos

Amorimia septentrionalis contém monofluoracetato de sódio e quando consumida por ruminantes provoca morte súbita. Este estudo teve o objetivo de relatar a epidemiologia, os sinais clínicos e patológicos de surtos de morte súbita em bovinos provocadas por Amorimia septentrionalis nos Estados de Pernambuco e Paraíba. Para isso, realizaram-se visitas técnicas em diversas propriedades nas Microrregiões do Médio Capibaribe/PE e Itabaiana/PB. Oito bovinos foram necropsiados. Coletaram-se tecidos das cavidades abdominal e torácica, além do encéfalo e medula espinhal. As alterações clínicas consistiram em lentidão, decúbito esternal prolongado, relutância em se movimentar quando em estação, cansaço, taquipneia, taquicardia e pulso venoso positivo. Os bovinos que foram forçados a se movimentar apresentaram instabilidade, tremores musculares e queda repentina seguida de vocalizações, movimentos de pedalagem e morte súbita em cerca de 5 a 7 minutos. As principais alterações macroscópicas consistiram em edema pulmonar, coração com aspecto globular com áreas esbranquiçadas, petéquias e equimoses no epicárdio, miocárdio e músculos papilares. À microscopia observou-se aumento da eosinofilia do citoplasma dos cardiomiócitos, núcleos picnóticos, cariorrexia, cariólise, perda das estriações, edema intersticial, infiltrado inflamatório intersticial mononuclear e áreas multifocais de fibrose cardíaca. Nos rins, constatou-se degeneração hidrópico vacuolar e necrose das células epiteliais em túbulos contorcidos. Os sinais clínicos foram semelhantes aos sinais clínicos já descritos em bovinos por plantas que contém MFA. As lesões macro e microscópicas descritas no coração e rins são de grande valor diagnóstico. A. septentrionalis é a principal planta tóxica de interesse pecuário nas microrregiões do Médio Capibaribe e Itabaiana devido às perdas econômicas diretas e indiretas que provoca na pecuária dessas regiões.

Effects and Safety of Xylitol on Middle Ear Epithelial Cells

OBJECTIVE: Xylitol is a natural sugar known to reduce dental decay. Recently, several epidemiology studies have also shown that xylitol can prevent acute otitis media in children. It is assumed that these effects are related to the inhibition of bacterial growth in the nasopharynx. However, the effects and safety of xylitol in middle ear epithelial cells, which play a key role in otitis media, have not been investigated. The present study was performed to investigate whether xylitol shows antiinflammatory or antioxidative effects on human middle ear epithelial cells and to assess its safety profile for clinical use. MATERIALS and METHODS: We induced inflammation in human middle ear epithelial cells (HMEEC) with lipopolysaccharide (LPS). After xylitol treatment, we measured expression levels of the inflammatory cytokines TNF-α and COX-2 and the mucin gene MUC5AC using semiquantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. Cell viability and morphological changes following xylitol treatment were investigated by 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MMT) assay, flow cytometry, and Hoechst 33342 staining in human middle ear epithelial cells and mouse inner ear cells. RESULTS: Inflammatory cytokines and mucin gene expression were unaffected by xylitol. In addition, xylitol showed neither antioxidative effects nor cytotoxicity and did not stimulate apoptosis or necrosis of human middle ear epithelial cells or inner ear cells, even at high doses.

Renal lymph circulation blockage alters the epithelial cell phenotype and tubular integrity: role of distinct regulation of BMP7 and TGF-β/Smads signaling pathway

To investigate the effect of lymph circulation blockage on the alteration of renal epithelial cell phenotype and the tubular integrity, as well as the underlying mechanisms. Wistar rats received left renal lymph ligation and right renal nephrectomy (KL group) or right renal nephrectomy without lymph ligation (KN group) and then were killed on day 14, day 28 and day 56. The urine, blood and kidney tissue were collected for the analysis of protein and gene expressions and morphological changes. The urine albumin and serum creatinine (Cr) in KL group were significantly increased compared with KN group. Masson and PAS staining indicated the epithelial cell degeneration, necrosis, sublethal loss and atrophy in KL rats, but not in KN group. Interestingly, from the atrophic tubules, some epithelial cells exhibited polarity changes with hypertrophy contrasting to the normal epithelial morphology of KN group throughout the experiment. By EM, ligated kidneys showed irregularly wrinkled basement membranes and epithelial cell swelling. Some intertubular areas of the KL kidney were expanded with fibrotic matrix and fibroblast-like cells. In line with these morphological changes, the fibroblast cell markers of FSP1 and α-SMA were markedly increased in contrast to the remarkable reduction in epithelial cell marker E-cadherin and tight junction protein ZO-1. Moreover, the TGF-β1/Smad2/3 signaling pathway was significantly activated in KL rats in contrast to a robust downregulation of BMP7/Smad5 signaling. Disturbance of renal lymphatic circulation resulted in the epithelial cell phenotypic alteration and impaired tubular integrity possibly via distinct regulation of TGFβ1/Smads and BMP7/Smad5 signaling pathway.

Lead- and cadmium-induced histopathological changes in gill, kidney and liver tissue of freshwater climbing perch Anabas testudineus (Bloch, 1792)

The objective of this study was to examine the toxicological effect of two major heavy metal pollutants, lead chloride (PbCl2) and cadmium chloride (CdCl2), in the freshwater climbing perch, Anabas testudineus. Fish were exposed to 1.0 and 2.0 mg/L both metals and histopathological changes in gill, kidney and liver tissues were studied. Major changes observed in gill tissue were epithelial lifting, proliferation of epithelial cells, fusion of secondary lamellae, hyperplasia and hypertrophy of mucous cells, and necrosis of epithelial cells. Cell necrosis, degenerated kidney tubules, congestion, lymphocytic infiltration and vacuolation were the major abnormalities observed in kidney tissue. The most conspicuous changes in liver were darker nucleoli, irregularly shaped hepatocytes with dilated blood capillaries, and focal as well as single necrosis. Fish specimens exposed to PbCl2 exhibited pronounced changes in all tissues examined compared with those exposed to CdCl2. It is evident from this study that heavy metals can cause significant histopathological changes in fish tissue.

Hypoxia Enhances Protective Effect of Placental-Derived Mesenchymal Stem Cells on Damaged Intestinal Epithelial Cells by Promoting Secretion of Insulin-Like Growth Factor-1

Apoptosis and necrosis of intestinal epithelial cells (IECs), induced by ischemia-reperfusion (I/R) injury, can lead to dysfunction of the intestinal barrier, which could cause multiple organ dysfunction syndromes. Mesenchymal stem cells (MSCs) have the potential of providing protective effects on damaged IECs via paracrine action. This study investigated whether hypoxia can enhance the protective effect of placental-derived MSCs (pMSCs) on H2O2-treated-caco2 cells, and explored the possible mechanism. The pMSCs isolated by tissue culture were fibroblast-like, positive for CD73, CD90 and CD105 and can differentiate into chondrocytes and endothelial cells. Five days after treatment with H2O2, the numbers of living caco2 cells significantly decreased. More live H2O2-treated-caco2 cells were observed in pMSCs hypoxia culture medium (pMSCs-HCM) than pMSCs normoxia culture medium (pMSCs-NCM), and the application of a specific antibody that blocked insulin-like growth factor-1 (IGF-1) leads to a significant decrease of the protective effect of pMSCs-HCM. Hypoxia can promote IGF-1 expression of pMSCs at mRNA and protein levels, and caco2 stably expressed IGF-1 receptor. Knocking down IGF-1 expression in pMSCs by siRNA resulted in a significant attenuation of the increase in apoptosis of H2O2-treated-caco2 cultured in pMSCs-HCM. In conclusion, hypoxia can increase the protective effect of pMSCs on H2O2-treated-caco2 cells via a promotion of their paracrine actions, and the key cytokine involved is IGF-1.

Lamb model of respiratory syncytial virus-associated lung disease: insights to pathogenesis and novel treatments.

Preterm birth is a risk factor for respiratory syncytial virus (RSV) bronchiolitis and hospitalization. The pathogenesis underlying this is not fully understood, and in vivo studies are needed to better clarify essential cellular features and molecular mechanisms. Such studies include analysis of lung tissue from affected human infants and various animal models. The preterm and newborn lamb lung has developmental, structural, cellular, physiologic, and immunologic features similar to that of human infants. Also, the lamb lung is susceptible to various strains of RSV that infect infants and cause similar bronchiolar lesions. Studies in lambs suggest that viral replication in airways (especially bronchioles) is extensive by 4 days after infection, along with bronchiolitis characterized by degeneration and necrosis of epithelial cells, syncytial cell formation, neutrophil infiltration, epithelial cell hypertrophy and hyperplasia, and innate and adaptive immune responses. RSV bronchiolitis greatly affects airflow and gaseous exchange. RSV disease severity is increased in preterm lambs compared with full-term lambs; similar to human infants. The lamb is conducive to experimental assessment of novel, mechanistic therapeutic interventions such as delivery of vascular endothelial growth factor and enhancement of airway epithelial oxidative responses, Club (Clara) cell protein 10, and synthesized compounds such as nanobodies. In contrast, exposure of the fetal ovine lung in vivo to ethanol, a risk factor for preterm birth, reduces pulmonary alveolar development and surfactant protein A expression. Because the formalin-inactivated RSV vaccination enhances some inflammatory responses to RSV infection in lambs, this model has the potential to assess mechanisms of formalin-inactivated RSV enhanced disease as well as newly developed vaccines.

Helicobacter pylorigamma-glutamyl transpeptidase and its pathogenic role

Helicobacter pylori (H. pylori) gamma-glutamyl transpeptidase (GGT) is a bacterial virulence factor that converts glutamine into glutamate and ammonia, and converts glutathione into glutamate and cysteinylglycine. H. pylori GGT causes glutamine and glutathione consumption in the host cells, ammonia production and reactive oxygen species generation. These products induce cell-cycle arrest, apoptosis, and necrosis in gastric epithelial cells. H. pylori GGT may also inhibit apoptosis and induce gastric epithelial cell proliferation through the induction of cyclooxygenase-2, epidermal growth factor-related peptides, inducible nitric oxide synthase and interleukin-8. H. pylori GGT induces immune tolerance through the inhibition of T cell-mediated immunity and dendritic cell differentiation. The effect of GGT on H. pylori colonization and gastric persistence are also discussed.

Cellular Inhibitor of Apoptosis Protein cIAP2 Protects against Pulmonary Tissue Necrosis during Influenza Virus Infection to Promote Host Survival

Cellular inhibitors of apoptosis proteins (cIAPs) are essential regulators of cell death and immunity. The corresponding contributions of IAPs to infectious disease outcomes are relatively unexplored. We find that mice deficient in cIAP2 exhibit increased susceptibility and mortality to influenza A virus infection. The lethality was not due to impaired antiviral immune functions, but rather because of death-receptor-induced programmed necrosis of airway epithelial cells that led to severe bronchiole epithelial degeneration, despite control of viral replication. Pharmacological inhibition of RIPK1 or genetic deletion of Ripk3, both kinases involved in programmed necrosis, rescued cIAP2-deficient mice from influenza-induced lethality. Genetic deletion of the deathreceptor agonists Fas ligand or TRAIL from the hematopoietic compartment also reversed the susceptibility of cIAP2-deficient mice. Thus, cIAP2-dependent antagonism of RIPK3-mediated programmed necrosis critically protects the host from influenza infection through maintenance of pulmonary tissue homeostasis rather than through pathogen control by the immune system.

Protective effect of resveratrol on arsenic trioxide-induced nephrotoxicity in rats.

BACKGROUD/OBEJECTIVESArsenic, which causes human carcinogenicity, is ubiquitous in the environment. This study was designed to evaluate modulation of arsenic induced cancer by resveratrol, a phytoalexin found in vegetal dietary sources that has antioxidant and chemopreventive properties, in arsenic trioxide (As2O3)-induced Male Wistar rats.MATERIALS/METHODSAdult rats received 3 mg/kg As2O3 (intravenous injection, iv.) on alternate days for 4 days. Resveratrol (8 mg/kg) was administered (iv.) 1 h before As2O3 treatment. The plasma and homogenization enzymes associated with oxidative stress of rat kidneys were measured, the kidneys were examined histologically and trace element contents were assessed.RESULTSRats treated with As2O3 had significantly higher oxidative stress and kidney arsenic accumulation; however, pretreatment with resveratrol reversed these changes. In addition, prior to treatment with resveratrol resulted in lower blood urea nitrogen, creatinine and insignificant renal tubular epithelial cell necrosis. Furthermore, the presence of resveratrol preserved the selenium content (0.805 ± 0.059 µg/g) of kidneys in rats treated with As2O3. However, resveratrol had no effect on zinc level in the kidney relative to As2O3-treated groups.CONCLUSIONSOur data show that supplementation with resveratrol alleviated nephrotoxicity by improving antioxidant capacity and arsenic efflux. These findings suggest that resveratrol has the potential to protect against kidney damage in populations exposed to arsenic.

Gross hematuria after kidney transplantation.

A 42-year-old male with a history of end-stage kidney disease secondary to diabetes mellitus type 1 received a deceased donor simultaneous kidney/pancreas transplant 10 months prior to presentation. The patient had prompt graft function and no other complications. He presented with gross hematuria and kidney allograft dysfunction with serum creatinine elevation from baseline of 114.92 to 221 µmol/L (1.3 to 2.5 mg/dL). Ultrasound and abdominal computed tomography were normal. Polyomavirus and cytomegalovirus (CMV) polymerase chain reaction (PCR) were negative. A kidney biopsy showed patchy necrotizing and vaguely granulomatous tubulointerstitial inflammation (Figure 1A). The infiltrate consisted of neutrophils, macrophages and lymphocytes with abundant epithelial cell destruction. Occasional epithelial cell nuclei had glassy chromatin suggestive of viral cytopathic effect (Figure 1B). Immunohistochemical staining for C4d, SV40, CMV and HSV was negative, while staining for adenovirus showed strong reactivity. Positivity of adenovirus PCR of more than 1 000 000 copy/mL confirmed the diagnosis of adenovirus tubulointerstitial nephritis. Immunosuppressive medications were reduced and one dose of cidofovir and intravenous immunoglobulin (IVIG) was given. Adenovirus PCR decreased to 175 000 after 1 week, and was no longer detected after 1 month. Creatinine gradually decreased to baseline over 3 months. Fig. 1. (A). Lower power image showing patchy tubulointerstitial inflammation (H&E, ×40). (B). Tubular epithelial cell necrosis (arrow heads), and a glassy viral inclusion (arrow) (H&E, ×400). Adenoviruses are non-enveloped double-stranded DNA viruses. Such virus presents as a self-limited respiratory, gastrointestinal and conjunctival disease in immunocompetent patients. In kidney transplant recipients, it manifests as allograft dysfunction, and hemorrhagic cystitis, but can result in severe fatal cases [1]. Infection is rare with an incidence rate of around 4% in kidney transplant recipients [2]. Infection can be de novo, or through reactivation of a latent infection of the recipient or from the allograft. Adenovirus serology is not routinely checked before transplantation, but serology mismatch might be a risk factor for infection [1]. The presence of patchy necrotizing infection, large nuclei with basophilic glassy inclusions and negativity of polyoma and CMV serology should suggest additional work-up for adenovirus, especially in the setting of hemorrhagic cystitis. A PCR offers a highly sensitive tool to confirm the infection and monitor the response of treatment [3]. Management starts with reduction of immunosuppressive medications. Severe cases might require one or two regimens of cidofovir, and administration of IVIG. Outcomes of reported cases showed that clearance of adenovirus viremia occurs within 1–3 weeks [2], and that there is an improvement in kidney allograft function to baseline or near baseline in the majority of cases [4].

Evidence for a morphologically distinct and functionally robust cell type in the proximal tubules of human kidney

Acute tubular necrosis (ATN), elicited by ischemia and/or toxicity, is a potentially life-threatening condition. Histologically, ATN corresponds to necrosis and detachment of renal tubular epithelial cells. However, the tubules possess a considerable regenerative capacity and may be restored. We have previously identified a scattered population of progenitor-like cells within the proximal tubules, sharing marker expression with the parietal epithelial cells of Bowman's capsule as well as with renal tubules regenerating after ATN. In the present analysis, we use transmission electron microscopy, immunoelectron microscopy and immunofluorescence of human kidney cortex to further explore these cells. We demonstrate that the cells are smaller and have drastically fewer mitochondria than the surrounding proximal tubule cells. They also display strong expression of several structural proteins such as vimentin, collagen-7A1 and the tight junction protein claudin-1. To functionally assess these cells, we also developed a novel human kidney explant model of ATN demonstrating that the cells are more resilient to injury than the surrounding proximal tubular cells. Taken together the results suggest a novel robust cell type with a contrasting biological role to that of the bulk of proximal tubular epithelium.

Nephritis Associated with a S1 Variant Brazilian Isolate of Infectious Bronchitis Virus and Vaccine Protection Test in Experimentally Infected Chickens

4 Abstract: Infectious bronchitis virus (IBV) induces a significant negative impact on poultry production worldwide, specially due to the continuous emergence of viral variants. This virus causes damage to th e respiratory tract, and depending on the virus strain, affects and damages the urogenital system. The objective of this study is to characterize the pathotype and the cross-immunity with regard to Massachusetts vaccine strain (H120) of a Brazilian IBV field isolate (IBVPR-05) previously S1 genotyped as a variant. The pathogenicity test was conducted on two experimental groups of specific pathogen free chickens; one was vaccinated with attenuated Massachusetts H120 strain and the other remained non-vaccinated. Three weeks after vaccination, both groups were challenged with IBRPR-05. The tracheal ciliostasis, and the viral load, histopathology and immunohistochemistry in trachea and kidney samples were evaluated. The viral loads, measured by quantitative real time RT-PCR, were higher in kidney than in trachea, and the most prominent histopathological changes were found in the kidneys. The renal lesions were characterized by the presence of nephritis with intense inflammation, tubular epithelial cell degeneration and necrosis. The H120 vaccine induced a partial protection against the infection of trachea and kidney tissues by this variant isolate. Thus, the Brazilian variant isolate IBVPR-05 was characterized in this study as a nephropathogenic pathotype and as a pr otectotype differing from Massachusetts vaccine strain of IBV. This indicates the importance to determine these biologic characteristics of other Brazilian variant IBV isolates, in order to implement more effective control measures of IBV infection in this country.

Carbaryl-induced Histopathologic Alterations in the Digestive Tract of the Levantine Frog, Pelophylax bedriagae (Anura: Ranidae)

In this study, histopathologic changes following carbaryl exposure for 96 hr were investigated in the digestive tract of Levantine frog, Pelophylax bedriagae. Adult frogs were exposed to carbaryl once by oral gavage in concentrations of 0.05, 0.1, and 0.2 mg/g. Histopathological changes were more prominent in medium- (0.1 mg/g) and high-dose (0.2 mg/g) groups than in the low-dose (0.05 mg/g) group. Esophageal cells showed vacuolization, cellular swelling, nuclear pyknosis, karyolysis, and necrosis. Additionally, esophageal glandular atrophy and infiltration of inflammatory cells around esophageal glands were observed at medium and high doses. In the stomach, there were prominent histopathologic defects such as cellular swelling and necrosis in gastric glands, necrotic cells within the interstitial spaces, separation of epithelial cell layer, congested vessels, and hemorrhage at medium and high doses. In the intestine, detachment of epithelial layer, epithelial cell disorganization, inflammation, and necrosis were detected at medium and high doses. The results of this study showed that carbaryl caused adverse effects on the digestive tract of the Levantine frog, P. bedriagae.

Acute and chronic nephrotoxicity of platinum nanoparticles in mice

Platinum nanoparticles are being utilized in various industrial applications, including in catalysis, cosmetics, and dietary supplements. Although reducing the size of the nanoparticles improves the physicochemical properties and provides useful performance characteristics, the safety of the material remains a major concern. The aim of the present study was to evaluate the biological effects of platinum particles less than 1 nm in size (snPt1). In mice administered with a single intravenous dose of snPt1, histological analysis revealed necrosis of tubular epithelial cells and urinary casts in the kidney, without obvious toxic effects in the lung, spleen, and heart. These mice exhibited dose-dependent elevation of blood urea nitrogen, an indicator of kidney damage. Direct application of snPt1 to in vitro cultures of renal cells induced significant cytotoxicity. In mice administered for 4 weeks with twice-weekly intraperitoneal snPt1, histological analysis of the kidney revealed urinary casts, tubular atrophy, and inflammatory cell accumulation. Notably, these toxic effects were not observed in mice injected with 8-nm platinum particles, either by single- or multiple-dose administration. Our findings suggest that exposure to platinum particles of less than 1 nm in size may induce nephrotoxicity and disrupt some kidney functions. However, this toxicity may be reduced by increasing the nanoparticle size.

English

  Consequent to injection of conidia at LC30, LC50 and LC90 doses of the entomopathogenic fungal isolates of Metarhizium anisopliae (Metch.), alterations in lipid peroxidation and ultrastructural changes were observed in cockroaches (Periplaneta americana). A decrease in the level of lipid peroxidation was evident in the treated cockroaches compared to those of control. Present investigation reports the effects of fungal infection on the midgut ultrastructure of the adult cockroaches which was manifested in the form of damage to the microvilli, epithelial cell vacuolization, necrosis and disruption of the epithelial cell membrane which occurred with increase in the time interval post treatment with conidia from high virulent isolate (M20) at LC50 dosage. Our study reveals for the first time that fungal infection instigates oxidative stress in the cockroach and that the villi of the midgut are also the target organs for the oxidative damage.   Key words: Entomopathogenic fungi, lethal concentration, cockroach, mid gut villi.

Pathogenesis of Newcastle Disease in Vaccinated Chickens: Pathogenicity of Isolated Virus and Vaccine Effect on Challenge of Its Virus

ABSTRACTThe pathogenicity of Newcastle disease (ND) virus, isolated from ND outbreak in vaccinated chickens, was evaluated through experiments. The pathogenicity indexes (mean death time (MDT); 58 hr, intracerebral pathogenicity index (ICPI); 1.7 and intravenous pathogenicity index (IVPI); 2.51) indicated that the ND virus was velogenic. The ND virus caused lymphocytic necrosis in the spleen with fibrinous exudation and proliferation of macrophages, sinusoidal fibrin exudation in the liver, proliferation of macrophages in the lung, lymphocytic necrosis and depletion in the bursa of Fabricius, cecal tonsils and thymus, necrosis of bone marrow, tracheitis, conjunctivitis and necrosis of feather epithelial cells in specific-pathogen-free chickens. Immunohistochemically, ND virus antigens were seen in the lesions mentioned above. The ND virus could not induce the encephalitis and pancreatitis that were observed in the natural case of ND in vaccinated chickens. There was no clinical disease in vaccinated chickens after the challenge of the ND virus. In diluted ND vaccine experiments, chickens vaccinated with a high dilution of vaccine and then challenged with the ND virus showed clinical sign and mortality with pancreatic focal necrosis. Vaccine diluted with fresh tap water had no effect on protection against the challenge of the ND virus. This study suggests that improper vaccination may be involved in outbreaks of ND in vaccinated chickens.

Oxidative stress in the kidney injury of mice following exposure to lanthanides trichloride

Environmental pollution from lanthanides (Ln) has been recognized as a major problem due to a grab exploitation of Ln mine in China. Exposure to Ln has been demonstrated to cause the nephrotoxicity, very little is known about the mechanism of oxidative damage to kidney in animals. In order to understand Ln-induced nephrotoxicity, various biochemical and chemical parameters were assayed in mouse kidney. Intragastric exposures of LaCl3, CeCl3, and NdCl3 at doses of 2, 5, and 10mgkg−1 BW for 90 consecutive days caused nephritis or epithelial cell necrosis and oxidative stress to kidney. An increase in coefficients of the kidney, La, Ce, and Nd accumulation and histopathological changes in the kidney could be observed, followed by increased reactive oxygen species production and peroxidation levels of lipid, protein and DNA, and decreased activities of superoxide dismutase, catalase, glutathione-S-transferase and glutathione reductase as well as antioxidants such as glutathione, ascorbic acid and thiol contents. Furthermore, La, Ce, and Nd significantly suppressed expression of genes and proteins of these antioxidative enzymes in mouse kidney. In addition, kidney functions were disrupted, including an increase of the creatinine, and reductions of uric acid, urea nitrogen, calcium and phosphonium. These findings suggest that nephritis generation or epithelial cell necrosis in mice following exposure to Ln is closely associated with oxidative stress. Of these damages, the most severe was in the Ce3+-exposed kidneys, next in the Nd3+-exposed kidneys, and the least in the La3+-exposed kidneys, which may be attributed to the 4f electron of Ln.