Streptococcus mutans induces IgA nephropathy-like glomerulonephritis in rats with severe dental caries

AbstractThe mechanisms underlying immunoglobulin A nephropathy (IgAN), the most common chronic form of primary glomerulonephritis, remain poorly understood. Streptococcus mutans, a Gram-positive facultatively anaerobic oral bacterium, is a common cause of dental caries. In previous studies, S. mutans isolates that express Cnm protein on their cell surface were frequently detected in IgAN patients. In the present study, inoculation of Cnm-positive S. mutans in the oral cavities of 2-week-old specific-pathogen free Sprague–Dawley rats fed a high-sucrose diet for 32 weeks produced severe dental caries in all rats. Immunohistochemical analyses of the kidneys using IgA- and complement C3-specific antibodies revealed positive staining in the mesangial region. Scanning electron microscopy revealed a wide distribution of electron dense deposits in the mesangial region and periodic acid-Schiff staining demonstrated prominent proliferation of mesangial cells and mesangial matrix. These results suggest that IgAN-like glomerulonephritis was induced in rats with severe dental caries by Cnm-positive S. mutans.

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P0371DENTAL CARIES INDUCED BY CNM-POSITIVE STREPTOCOCCUS MUTANS DERIVED FROM IGA NEPHROPATHY PATIETNS IN RATS INDUCED GLOPERULONEPHRITIS LIKE IGA NEPHROPATHY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0371 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Yasuyuki Nagasawa ◽

Shuhei Naka ◽

Kaoruko Wato ◽

Ryota Nomura ◽

Taro Misaki ◽

...

Keyword(s):

Dental Caries ◽

Iga Nephropathy ◽

Streptococcus Mutans ◽

Periodic Acid ◽

Sprague Dawley ◽

Periodic Acid Schiff ◽

Plaque Score ◽

Dense Deposit ◽

Sprague Dawley Rats ◽

Electron Microscopy Analysis

Abstract Background and Aims IgA nephropathy (IgAN) is one of most common primary glomerulonephritis, whose pathogenesis had remained unclear. We had reported that Cnm-(+)Streptococcus mutans, a kinds of major dental caries bacteria. Cnm-(+)S. mutans had strong collagen binding ability, resulting in high pathogenicity. We reported that the prevalence of Cnm-(+)S. mutans in IgA nephropathy is significantly higher than that in control (Misaki-T et al, Clin Exp Nephrol 2015; 19:844-50), and that Cnm-(+)S. mutans in IgA nephropathy was associated with proteinuria (Misaki-T et al, Sci Rep 2016). We also reported C.rectus and S. mutans increased proteinuria synergistically (Misaki-T et al, Nephron, 2018). In this point, there is no direct evidence that Cnm-(+)S. mutans could induce IgA nephropathy. In this study, we evaluated the renal lesions in rats which had dental caries induced by Cnm-(+)S. mutans derived from IgA nephropathy patient to confirm the pathogenesis of IgA nephropathy like lesions induced by Cnm-(+)S mutans. Method Cmn-(+)S. mutans from saliva of IgA nephropathy patients was orally administrated into 4 weeks old male Sprague-Dawley rats. Addition of sugar to water had been kept during study period to develop dental carits. At week 34 after the infection, blood, urine, and kidney samples were evaluated. Kidney samples were stained by Periodic Acid-Schiff (PAS), IgA, C3. Historical evaluation by electron microscope analysis was also performed. Results At week 34, plaque score and dental caries score in infectious rats significantly elevated, compared with control rats (P<0.001) (Figure 1). These findings suggested Cmn-(+)S. mutans from IgA nephropathy patients induced dental caries in rats. PAS staining revealed the significant mesangial proliferation. At week 34, the prevalence of IgA deposition in infections rats was higher than that in control rats (52.4% vs 4%), and the prevalence of C3 deposition in infectious rats was also higher than that in control rats (42% vs 11%) (Figure 2). Incidence of hematuria was also significantly higher in dental caries group than control. Electron microscopy analysis revealed high dense deposit in mesangial areas. Conclusion Cmn-(+)S. mutans from saliva of IgA nephropathy patients could induce IgA-dominant infection-associated glomerulonephritis, or IgA nephropathy.

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Podoendin. A new cell surface protein of the podocyte and endothelium.

Journal of Experimental Medicine ◽

10.1084/jem.162.1.245 ◽

1985 ◽

Vol 162 (1) ◽

pp. 245-267 ◽

Cited By ~ 26

Author(s):

T W Huang ◽

J C Langlois

Keyword(s):

Cell Surface ◽

Periodic Acid ◽

Polyacrylamide Gel Electrophoresis ◽

Surface Protein ◽

Complement C3 ◽

Renal Tubules ◽

Cell Surface Protein ◽

Sprague Dawley ◽

Colloidal Iron ◽

Periodic Acid Schiff

A new cell surface protein, podoendin, has been identified in Sprague-Dawley rats, and isolated using monoclonal antibody (mAb) G4. The distribution of podoendin is restricted to the surface of glomerular podocytes, urinary surface of the parietal epithelium of Bowman's capsule, and the luminal surface of endothelial cells. The antibody does not crossreact with podocytes or endothelia of human or mice. In newborn rats, the appearance of podoendin on glomerular epithelium is attendant on podocyte differentiation during glomerulogenesis of metanephrogenic vesicles. It disappears when podocytes retract and efface foot processes in tissue culture. Thus, podoendin appears to be a cell differentiation-dependent surface protein of podocytes. Podoendin is a protein of 62 kD mobility on 5% polyacrylamide gel electrophoresis. It stains intensely with Coomassie blue, but gives negative reactions to carbohydrate (periodic acid/Schiff reaction) and polyanions (alcian blue, colloidal iron, and carbocyanine). It is distinct from the major sialoglycoprotein of podocyte fuzzy coat, podocalyxin (11). Podoendin isolated and purified from endothelium of lungs appears to be identical with that from podocytes and endothelium of kidneys. Injection of mAb G4 into left ventricle of rats resulted in intense decoration of the endothelium and podocyte surface within 30 min. The decoration persisted throughout the 3-d period of observation. This was not accompanied by complement (C3) fixation. Preliminary results showed that the rats developed moderate proteinuria (100 mg/ml protein in urine), which was associated with the presence of hyaline droplets in renal tubules, on the third day. The proteinuria was not accompanied by effacement of podocyte pedicels. There were no morphologic alterations indicating glomerular or vascular injury in the kidneys.

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Effects of matrix metalloproteinase inhibitor on LPS-induced goblet cell metaplasia

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00047.2003 ◽

2004 ◽

Vol 287 (1) ◽

pp. L127-L133 ◽

Cited By ~ 38

Author(s):

Je Hyeong Kim ◽

Sung Yong Lee ◽

Sang Myeon Bak ◽

In Bum Suh ◽

Sang Yeub Lee ◽

...

Keyword(s):

Goblet Cell ◽

Bacterial Infections ◽

Inflammatory Responses ◽

Periodic Acid ◽

Growth Factor Receptor ◽

Sprague Dawley ◽

Neutrophilic Infiltration ◽

Periodic Acid Schiff ◽

Mucus Hypersecretion ◽

Egfr Expression

Bacterial infections of the lung are known to induce inflammatory responses, which lead to mucus hypersecretion. Moreover, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and its activation. Furthermore, matrix metalloproteinases (MMPs), especially MMP-9, have been reported to promote the transmigration of activated neutrophils. In this study, we investigated the associations between lipopolysaccharide (LPS)-induced goblet cell (GC) metaplasia and EGFR expression and the effects of MMP inhibitor (MMPI). Various concentrations of LPS were instilled into the tracheas of pathogen-free Sprague-Dawley rats, and airways were examined at different times after LPS instillation. To examine the role of MMP-9, we treated rats 3 days before LPS instillation and daily thereafter with MMPI. Neutrophilic infiltration, Alcian blue/periodic acid-Schiff (AB/PAS) staining, and immunohistochemical staining for MUC5AC, EGFR, and MMP-9 were performed. The instillation of LPS increased AB/PAS and MUC5AC staining in time- and dose-dependent manners, and treatment with MMPI significantly prevented GC metaplasia. The instillation of LPS into the trachea also induced neutrophilic infiltration and EGFR and MMP-9 expression in the airway epithelium, and MMPI was found to significantly prevent neutrophil recruitment, GC metaplasia, and EGFR and MMP-9 expression. This study demonstrates that the MMP-9 and EGFR cascades are associated with LPS-induced mucus hypersecretion.

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Intranasal Immunization against Dental Caries with a Streptococcus mutans-Enriched Fimbrial Preparation

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.6.3.405-409.1999 ◽

1999 ◽

Vol 6 (3) ◽

pp. 405-409 ◽

Cited By ~ 15

Author(s):

Margherita Fontana ◽

Ann J. Dunipace ◽

George K. Stookey ◽

Richard L. Gregory

Keyword(s):

Dental Caries ◽

Cholera Toxin ◽

Streptococcus Mutans ◽

Surface Proteins ◽

Mucosal Vaccine ◽

Tooth Surface ◽

Cholera Toxin B Subunit ◽

Sprague Dawley ◽

Igg Antibody ◽

Group A

ABSTRACT Streptococcus mutans has been identified as the major etiological agent of human dental caries. The first step in the initiation of infection by this pathogenic bacterium is its attachment (i.e., through bacterial surface proteins such as glucosyltransferases, P1, glucan-binding proteins, and fimbriae) to a suitable receptor. It is hypothesized that a mucosal vaccine against a combination ofS. mutans surface proteins would protect against dental caries by inducing specific salivary immunoglobulin A (IgA) antibodies which may reduce bacterial pathogenesis and adhesion to the tooth surface by affecting several adhesins simultaneously. Conventional Sprague-Dawley rats, infected withS. mutans at 18 to 20 days of age, were intranasally immunized with a mixture of S. mutans surface proteins, enriched for fimbriae and conjugated with cholera toxin B subunit (CTB) plus free cholera toxin (CT) at 13, 15, 22, 29, and 36 days of age (group A). Control rats were either not immunized (group B) or immunized with adjuvant alone (CTB and CT [group C]). At the termination of the study (when rats were 46 days of age), immunized animals (group A) had significantly (P < 0.05) higher salivary IgA and serum IgG antibody responses to the mixture of surface proteins and to whole bacterial cells than did the other two groups (B and C). No significant differences were found in the average numbers of recoveredS. mutans cells among groups. However, statistically fewer smooth-surface enamel lesions (buccal and lingual) were detected in the immunized group than in the two other groups. Therefore, a mixture of S. mutans surface proteins, enriched with fimbria components, appears to be a promising immunogen candidate for a mucosal vaccine against dental caries.

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Effects of Periostracum Cicadae on Cytokines and Apoptosis Regulatory Proteins in IgA Nephropathy Rat Model

10.20944/preprints201805.0337.v1 ◽

2018 ◽

Author(s):

Lu Yang ◽

Yan Wang ◽

Aobulikasimu Nuerbiye ◽

Ping Cheng ◽

Jin-Hui Wang ◽

...

Keyword(s):

Iga Nephropathy ◽

Interleukin 1 ◽

Periodic Acid ◽

Immunoglobulin A ◽

Blood Stasis ◽

Lavage Fluid ◽

Enzyme Linked Immunosorbent Assay ◽

Periodic Acid Schiff ◽

Protein Levels ◽

Related Proteins

Periostracum cicadae, the cast-off shell of the cicada Cryptotympana pustulata Fabricius, is used in traditional Chinese medicine for its diaphoretic, anticonvulsive, sedative, antipyretic, and antiallergic effects. However, the exact pathogenesis of immunoglobulin A nephropathy (IgAN) remains unclear, thereby hindering investigations to identify novel therapeutic agents. A rat IgAN model was established by administration of bovine serum albumin, lipopolysaccharide, and carbon tetrachloride, which simultaneously established blood stasis and a heat syndrome model. The animals were sacrificed to detect changes in protein levels in urine and blood. Immunofluorescence was performed to assess IgA deposition in the glomeruli. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6) levels were measured in bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assay. Hematology and eosin, periodic acid-Schiff, TUNEL, and immunohistochemical staining were performed to evaluate histopathological changes in kidney tissues. Additionally, target-related proteins were measured by western blotting. Periostracum cicadae resulted in a reduction in blood and urine protein levels. Serum TNF-α, IL-1β, and IL-6 levels significantly decreased in the periostracum cicadae-treated groups compared to the IgAN group. Furthermore, a reduction in MCP-1, TLR4, and IgA expression levels and a dose- dependent increase in caspace-3 expression were observed in response to periostracum cicadae treatment. TGF-β1 levels decreased, whereas that of Fas increased in the kidney tissues of the periostracum cicadae-treated groups. The findings of the present study indicate that periostracum cicadae induces apoptosis and improves kidney inflammation and fibrosis in IgA nephropathy rat models.

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The adverse effect of long term intake of Monosodium Glutamate on kidney performance

IOP Conference Series Earth and Environmental Science ◽

10.1088/1755-1315/880/1/012056 ◽

2021 ◽

Vol 880 (1) ◽

pp. 012056

Author(s):

Amer M. Hussin ◽

Ali A. Tala’a ◽

Safa Abdul Naser Fadhil ◽

Hamzah Abdulrahman Salman

Keyword(s):

Mesangial Cells ◽

Periodic Acid ◽

Monosodium Glutamate ◽

Environmental Pollutant ◽

Basement Membranes ◽

Male Rats ◽

Periodic Acid Schiff ◽

Histological Techniques ◽

Treatment Groups

Abstract Monosodium glutamate (MSG) is a food additive that is considered as a water and environmental pollutant and affects the tissues of the living being. This study was aimed to find the effect of long-term administration of MSG on the mass of mesangial cells of the kidneys. Forty adult male rats were divided into four groups (10 each). Control groups 1&2 were supplied orally with distilled water for 30 and 60 days, respectively. Treatment groups 1&2 were supplied orally with 15 mg/kg Bwt of MSG for 30 & 60 days, respectively. Control and treatment groups were sacrificed, specimens of kidneys were obtained, fixed with 10% neutral buffered formalin, processed by Routine histological techniques, stained by Hematoxylin and eosin, and PAS (Periodic Acid-Schiff) stains then examined under the light microscope. The result found enlargement in a mesangial mass represented by hypertrophy and hyperplasia of mesangial cells leading to mesangial proliferative glomerulonephritis. Accordingly, the study showed an increase in creatinine values, indicating a disturbance in renal function. This will lead to a decrease in the sizes of the glomeruli of renal corpuscles and a relative increase of Bowman’s space. With the time of the experiment, the glomerular capillaries and gates of basement membranes will be closed, resulting in renal filtration disorders. It was concluded that the long-term intake of MSG leads to indirect narrowing of the glomerular capillary lumen, causing kidney failure.

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Food additive “lauric acid” possess non-toxic profile on biochemical, haematological and histopathological studies in female Sprague Dawley (SD) rats

PeerJ ◽

10.7717/peerj.8805 ◽

2020 ◽

Vol 8 ◽

pp. e8805 ◽

Cited By ~ 1

Author(s):

Hidayat Ullah Khan ◽

Khurram Aamir ◽

Sreenivas Patro Sisinthy ◽

Narendra Babu Shivanagere Nagojappa ◽

Aditya Arya

Keyword(s):

Body Weight ◽

Lauric Acid ◽

Biochemical Analysis ◽

Periodic Acid ◽

Food Additives ◽

Sprague Dawley ◽

Oral Toxicity ◽

Periodic Acid Schiff ◽

Sd Rats ◽

Study Results

Background Lauric acid (LA), a common constituent of coconut oil, is used as food additives and supplements in various formulations. Despite various potential pharmacological properties, no scientific evidence on its dose-related toxicity and safety is available till date. Objective The current study was conducted to evaluate acute oral toxicity of LA on normal rats. Methods The study was conducted in accordance with the Organization for Economic Co-operation and Development guidelines (OECD 423) with slight modifications. LA was administered orally to female Sprague Dawley (SD) rats (n = 6/group) at a single dose of 300 and 2,000 mg/kg body weight, respectively, while normal control received vehicle only. Animals from all the three groups were monitored for any behavioural and toxicological changes and mortality for two weeks. Food and fluid consumption, body weight was monitored on daily basis. At the end (on day 15th) of the experimental period, blood was collected for haematological and biochemical analysis. Further, all the animals were euthanized, and internal organs were harvested for histopathological investigation using four different stainings; haematoxylin and eosin, Masson trichrome, Periodic Acid Schiff and Picro Sirius Red for gross pathology through microscopical observation. Results The study results showed no LA treatment-related mortality and morbidity at two different dosages. Daily food and water consumption, body weight, relative organ weight, haematological, and biochemical analysis were observed to be normal with no severe alterations to the internal tissues. Conclusion The current finding suggests that single oral administration of LA, even up to 2,000 mg/kg body weight, did not exhibit any signs of toxicity in SD rats; thus, it was safe to be used on disease models in animals.

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Intravenous administration of Streptococcus mutans induces IgA nephropathy-like lesions

Clinical and Experimental Nephrology ◽

10.1007/s10157-020-01961-1 ◽

2020 ◽

Vol 24 (12) ◽

pp. 1122-1131

Author(s):

Shuhei Naka ◽

Kaoruko Wato ◽

Taro Misaki ◽

Seigo Ito ◽

Yasuyuki Nagasawa ◽

...

Keyword(s):

Iga Nephropathy ◽

Streptococcus Mutans ◽

Intravenous Administration ◽

Mesangial Cells ◽

Late Phase ◽

Control Group ◽

Chronic Glomerulonephritis ◽

Sprague Dawley ◽

Mesangial Area ◽

Specific Pathogen

Abstract Background IgA nephropathy (IgAN) is one of the most frequently occurring types of chronic glomerulonephritis. Previous analyses have revealed that a major pathogen of dental caries, Streptococcus mutans [which expresses collagen-binding protein (Cnm) on its surface], is involved in the pathogenesis of IgAN. Methods Cnm-positive S. mutans isolated from a patient with IgAN was intravenously administered to specific pathogen-free Sprague–Dawley rats to evaluate their kidney conditions. Results The urinary protein level of the S. mutans group reached a plateau at 30 days, with increased numbers of mesangial cells and an increased mesangial matrix. The numbers of rats with IgA-positive and/or C3-positive glomeruli were significantly greater in the S. mutans group than in the control group at 45 days (P < 0.05). Electron microscopy analyses revealed electron-dense depositions in the mesangial area among rats in the S. mutans group. There were significantly more CD68-positive cells (macrophages) in the glomeruli of the S. mutans group than in the glomeruli of the control group during the late phase (P < 0.05), similar to the findings in patients with IgAN. Conclusion Our results suggested that intravenous administration of Cnm-positive S. mutans caused transient induction of IgAN-like lesions in rats.

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Bilateral Renal Oncocytoma in a Greyhound Dog

Veterinary Pathology ◽

10.1354/vp.37-2-188 ◽

2000 ◽

Vol 37 (2) ◽

pp. 188-192 ◽

Cited By ~ 20

Author(s):

C. D. Buergelt ◽

A. Adjiri-Awere

Keyword(s):

Tumor Cells ◽

Periodic Acid ◽

Renal Oncocytoma ◽

Positive Staining ◽

Immunohistochemical Expression ◽

Periodic Acid Schiff ◽

Schiff Reaction

A bilateral, locally invasive renal oncocytoma was diagnosed in a 10-year-old spayed female Greyhound dog. The diagnosis was based on positive staining of the tumor with the periodic acid-Schiff reaction prior to diastase treatment, on the immunohistochemical expression of cytoplasmic cytokeratin, and on the prominence of mitochondria in the tumor cells.

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Gastroprotective Activity ofPolygonum chinenseAqueous Leaf Extract on Ethanol-Induced Hemorrhagic Mucosal Lesions in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/404012 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 24

Author(s):

Iza Farhana Ismail ◽

Shahram Golbabapour ◽

Pouya Hassandarvish ◽

Maryam Hajrezaie ◽

Nazia Abdul Majid ◽

...

Keyword(s):

Leaf Extract ◽

Reference Group ◽

Periodic Acid ◽

Mucosal Injury ◽

Distilled Water ◽

Sprague Dawley ◽

Periodic Acid Schiff ◽

Intense Staining ◽

Ulcer Group ◽

Aqueous Leaf Extract

Polygonum chinenseis a Malaysian ethnic plant with various healing effects. This study was to determine preventive effect of aqueous leaf extract ofP. chinenseagainst ethanol-induced gastric mucosal injury in rats.Sprague Dawleyrats were divided into seven groups. The normal and ulcer control groups were orally administered with distilled water. The reference group was orally administered with 20 mg/kg omeprazole. The experimental groups received the extracts 62.5, 125, 250, and 500 mg/kg, accordingly. After sixty minutes, distilled water and absolute ethanol were given (5 mL/kg) to the normal control and the others, respectively. In addition to histology, immunohistochemical and periodic acid schiff (PAS) stains, levels of lipid peroxidation, malondialdehyde (MDA), antioxidant enzymes, and superoxide dismutase (SOD) were measured. The ulcer group exhibited severe mucosal damages. The experimental groups significantly reduced gastric lesions and MDA levels and increased SOD level. Immunohistochemistry of the experimental groups showed upregulation and downregulation of Hsp70 and Bax proteins, respectively. PAS staining in these groups exhibited intense staining as compared to the ulcer group. Acute toxicity study revealed the nontoxic nature of the extract. Our data provide first evidence thatP. chinenseextract could significantly prevent gastric ulcer.

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