Overgrowth In Rats Research Articles

Targeting SRD5A1 and MMP-2/NLRP3/TGF-β1 axis alleviates the amlodipine-induced gingival hyperplasia in rats: Emerging role of saw palmetto and folic acid

Saw palmetto (SAW), the herbal drug used to treat prostatic hyperplasia, exerts its antiproliferative effects by blocking steroid 5 alpha-reductase (SRD5A1) activity, that has also been involved in gingival hyperplasia (GH) pathogenesis. Concurrently, folic acid (FA) could reduce GH prevalence via its antioxidant and anti-inflammatory effects. Thus, this study tended to assess the potential therapeutic efficacy of SAW, alone and along with FA, against amlodipine-induced gingival inflammation and overgrowth in rats. Rats were grouped into (CONT, AIGH, SAW, SAW-treated, FA-treated, and SAW + FA-treated). SAW and FA were administered once daily for 4 weeks. Gingival SRD5A1, CTGF, GSK-3β, and NLRP3 expressions, as well as T, DHT, MDA, TAC, ET-1, and MMP2 levels were determined. In addition, histopathological and immunohistochemical analyses of TNF-α, IL-6, TGF-β1, and α-SMA were documented. Results declared that SAW and FA administration markedly ameliorated amlodipine-associated GH and may be presenting a novel therapeutic avenue in the future.

Blockage of the adenosine A2B receptor prevents cardiac fibroblasts overgrowth in rats with pulmonary arterial hypertension

Sustained pressure overload and fibrosis of the right ventricle (RV) are the leading causes of mortality in pulmonary arterial hypertension (PAH). Although the role of adenosine in PAH has been attributed to the control of pulmonary vascular tone, cardiac reserve, and inflammatory processes, the involvement of the nucleoside in RV remodelling remains poorly understood. Conflicting results exist on targeting the low-affinity adenosine A2B receptor (A2BAR) for the treatment of PAH mostly because it displays dual roles in acute vs. chronic lung diseases. Herein, we investigated the role of the A2BAR in the viability/proliferation and collagen production by cardiac fibroblasts (CFs) isolated from RVs of rats with monocrotaline (MCT)-induced PAH. CFs from MCT-treated rats display higher cell viability/proliferation capacity and overexpress A2BAR compared to the cells from healthy littermates. The enzymatically stable adenosine analogue, 5′-N-ethylcarboxamidoadenosine (NECA, 1–30 μM), concentration-dependently increased growth, and type I collagen production by CFs originated from control and PAH rats, but its effects were more prominent in cells from rats with PAH. Blockage of the A2BAR with PSB603 (100 nM), but not of the A2AAR with SCH442416 (100 nM), attenuated the proliferative effect of NECA in CFs from PAH rats. The A2AAR agonist, CGS21680 (3 and 10 nM), was virtually devoid of effect. Overall, data suggest that adenosine signalling via A2BAR may contribute to RV overgrowth secondary to PAH. Therefore, blockage of the A2AAR may be a valuable therapeutic alternative to mitigate cardiac remodelling and prevent right heart failure in PAH patients.

High-dose D-glucosamine Consumption Increases Serum and Cecum Levels of Ammonia and Ethanol and Causes Bacterial Overgrowth in Rats

High-dose D-glucosamine Consumption Increases Serum and Cecum Levels of Ammonia and Ethanol and Causes Bacterial Overgrowth in Rats

Diet Enriched with Olive Oil Attenuates Placental Dysfunction in Rats with Gestational Diabetes Induced by Intrauterine Programming

Offspring from rats with mild diabetes develop gestational diabetes mellitus (GDM). We tested the hypothesis that an olive oil-supplemented diet attenuates placental oxidative stress/inflammation, activation of mTOR signaling, and inhibition of peroxisome proliferator-activated receptor γ (PPARγ) and fetal overgrowth in GDM offspring from mild diabetic rats. Female offspring from rats with mild diabetes (group that developed GDM) and controls were fed with either a standard diet or a 6% olive oil-supplemented diet during pregnancy. On day 21 of pregnancy, plasma glucose levels in mothers and fetuses were increased in the GDM group independently of the diet. Fetal overgrowth and activation of placental mTOR signaling were partially prevented in the olive oil-treated GDM group. Placental PPARγ protein expression was decreased in GDM rats, independently of the diet. However, increases in placental lipoperoxidation, connective tissue growth factor, and matrix metalloproteinase 2 levels were prevented by the olive oil-enriched diet. Diets enriched with olive oil attenuate placental dysfunction and fetal overgrowth in rats with GDM induced by intrauterine programming.

Tanshinone IIA treatment alleviated the rat gingival connective tissue overgrowth induced by cyclosporine A.

The use of cyclosporine A induces fibrous enlargement of the gingival connective tissue. Existing treatment modalities, although effective, do not necessarily prevent the recurrence of the lesion. Emerging evidence indicates that tanshinone IIA (Tan IIA) could effectively attenuate a variety of fibrotic diseases. The present research aims to assess whether Tan IIA can effectively alleviate the gingival fibrous overgrowth induced by cyclosporine A. Forty-five Wistar rats were divided into the no-treatment control group, cyclosporine A-treated group and the group treated with a combination of cyclosporine A and Tan IIA. Paraffin-embedded sections of mandibular first molar regions were selected for hematoxylin and eosin staining, Masson's trichrome staining, picro-sirius red staining and immunohistochemistry analyses of transforming growth factor-β1 (TGF-β1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-1 (MMP-1). The gingival connective tissue area was measured and numbers of the TGF-β1-, TIMP-1- and MMP-1-positive cells were counted. The analysis of variance for factorial designs for testing the overall differences and Fisher least significant difference test for post hoc analysis were used to determine the significance levels. Cyclosporine A treatment led to overgrowth of gingival connective tissue in rats. In the cyclosporine A-treated rats, the expression of TGF-β1 and TIMP-1 was significantly upregulated, whereas expression of the MMP-1 was downregulated, along with thicker and denser collagen fibers. In rats treated with a combination of cyclosporine A and Tan IIA, the cyclosporine A-induced changes were alleviated. Cyclosporine A enhanced gingival fibrous overgrowth via upregulation of the TGF-β1 and TIMP-1 expression, and downregulation of MMP-1 expression. Tan IIA can effectively prevent cyclosporine A-induced gingival fibrous overgrowth in rats by downregulating TGF-β1 and TIMP-1 expression, and upregulating MMP-1 expression.

Local Inflammation Alters MMP-2 and MMP-9 Gelatinase Expression Associated with the Severity of Nifedipine-Induced Gingival Overgrowth: a Rat Model Study

Nifedipine-induced gingival overgrowth (NIGO) is characterized by cell proliferation and extracellular matrix (ECM) component accumulation in gingival connective tissues, with varying degrees of inflammation and fibrosis. Impaired collagen and ECM homeostasis may be among the underlying molecular mechanisms that lead to the fibrotic changes that occur in drug-induced gingival overgrowth (DIGO). Because matrix metalloproteinases (MMPs) play vital roles in regulating collagen and ECM metabolism, many studies have been performed to reveal the relationship between MMPs and DIGO. It is thought that the gelatinases MMP-2 and MMP-9, both type IV collagenases, are involved in the development of tissue inflammation and organ fibrosis. However, the few studies regarding gelatinase expression in DIGO are controversial. Recent studies have demonstrated the inhibitory effect of cyclosporine A (CsA) on gelatinase expression and/or activity; however, similar changes have yet to be detected in Nif-treated gingival tissues. In this study, we verified that Nif treatment could lead to gingival overgrowth in rats and that gingival inflammation played a pro-proliferative role in NIGO development. Additionally, we examined the temporal expression of gelatinases on days 0, 7, 14, 21, 30, and 40 during NIGO development. The aim was to investigate whether MMP-2 and MMP-9 played significant roles in regulating NIGO development and progression. MMP-2 gene expression was not altered by Nif treatment alone but was significantly inhibited by Nif treatment for 30days in the presence of local inflammation. However, no significant alterations in MMP-2 protein expression were detected in the Nif-treated gingival tissue, regardless of the presence or absence of local inflammation. Moreover, Nif treatment could lead to transient and significant increases in MMP-9 gene and protein expression levels in the presence of local inflammation. In particular, active MMP-9 expression increased significantly in the gingival tissue that received the combined effect of Nif and ligation treatment; besides, a temporal, but not significant, change was also observed in the gingival tissue that received Nif treatment alone. Taken together, these results provided evidence that temporal changes in MMP-2 and MMP-9 expression occurred during NIGO development. Nif treatment accompanied by local inflammation regulated MMP-2 and MMP-9 expression, primarily MMP-9, which was most likely associated with NIGO severity. Thus, MMP-9 is a potential contributing factor in the process of NIGO development.

Effect of concomitant administration of nifedipine and tacrolimus on the development of gingival overgrowth in rats

Background/purposeIt is still controversial whether tacrolimus can induce gingival overgrowth. Calcium channel blockers of nifedipine are commonly used for lessening the side effect of high blood pressure induced by tacrolimus; however, nifedipine can also induce gingival overgrowth. This study was conducted to evaluate the effect of concomitant administration of nifedipine and tacrolimus on gingival overgrowth in rats. Materials and methodsThirty-six Sprague-Dawley rats were assigned into four groups, including a control group. In drug groups, either tacrolimus (1.5 mg/kg) or nifedipine (30 mg/kg), or both drugs together were administrated daily for 6 weeks. The gingival morphology was examined macroscopically on the mandibular central papilla from cast models biweekly, and analyzed by measuring the sulcular probing depth and the keratinized gingival width around the first mandibular molars immediately after sacrificing. By histology, changes of papillae, including the connective tissue, and the epithelial and total tissue areas, were measured at two different tissue levels. ResultsSignificant increases in papillary dimensions, including depth, width, and height, were observed across all groups after Week 1, with the control group showing less changes than experimental drug groups. Among drug groups, significantly increased papillary dimensions were noted in the nifedipine group when compared with groups treated with tacrolimus and both drugs. Changes in keratinized gingival width were found to be similar in the tacrolimus and combined-drug groups but greater in the nifedipine group. For probing depth, experimental groups showed greater changes than the control group, but no difference was observed among the experimental groups. Similar trends were presented for the total and connective tissue areas; however, the epithelial tissue areas did not show any difference among the four treatment groups. ConclusionGingival overgrowth could be induced either by nifedipine or by tacrolimus, although the extent of gingival overgrowth induced by tacrolimus would be less than that by nifedipine. However, a concomitant administration of nifedipine and tacrolimus did not aggravate the induced gingival overgrowth.

Down-regulation of transforming growth factor beta-2 expression is associated with the reduction of cyclosporin induced gingival overgrowth in rats treated with roxithromycin: an experimental study

BackgroundGingival overgrowth (GO) is a common side effect of the chronic use of cyclosporine (CsA), an immunosuppressant widely used to prevent rejection in transplant patients. Recent studies have reported elevated levels of specific cytokines in gingival overgrowth tissue, particularly TGF-beta, suggesting that this growth factor plays a role in the accumulation of extracellular matrix materials. The effectiveness of azithromycin, a macrolide antibiotic, in the regression of this undesirable side effect has also been demonstrated.MethodsIn this study, we created an experimental model for assessing the therapeutic effect of roxithromycin in GO and the expression of transforming growth factor beta (TGF-beta2) through immunohistochemistry. We used four groups of rats totaling 32 individuals. GO was induced during five weeks and drug treatment was given on the 6th week as follows: group 1 received saline; group 2 received CsA and was treated with saline on the 6th week; group 3 received CsA and, on the 6th week, ampicilin; and group 4 received CsA during 5 weeks and, on the 6th week, was treated with roxithromycin.ResultsThe results demonstrated that roxithromycin treatment was effective in reducing cyclosporine-induced GO in rats. Both epithelial and connective tissue showed a decrease in thickness and a significant reduction in TGF-beta2 expression, with a lower number of fibroblasts, reduction in fibrotic areas and decrease in inflammatory infiltrate.ConclusionThe present data suggest that the down-regulation of TGF-beta2 expression may be an important mechanism of action by which roxithromycin inhibits GO.

Local Inflammation Exacerbates Cyclosporine A-Induced Gingival Overgrowth in Rats

Gingival overgrowth (GO) is a common side effect of long-term cyclosporine A (CsA) treatment. The risk factors appraised include drug interactions with calcium channel blockers, age, cyclosporine dose, dental bacterial plaque, duration of treatment, and genetic predisposition. The relationship and mechanism between GO and local inflammation caused by dental bacterial plaque have not been clearly defined. This research was carried out to investigate the histomorphometrical alterations and serum levels of transforming growth factor beta1 (TGF-beta1) in CsA-induced GO with or without local inflammation. Thirty-four male Sprague-Dawley rats were divided into 4 groups: Group I (control); Group II (ligation); Group III (CsA); Group IV (ligation and CsA). After 9 weeks the rats were sacrificed. The morphological examination was made and the histological changes with hematoxylin and eosin (HE) staining were observed. TGF-beta1 levels in serum were detected by enzyme-linked immunosorbent assay (ELISA). We report here that obvious GO are found in Group III and Group IV after CsA treatment, especially those rats with existed gingivitis presented an aggravation of GO. TGF-beta1 levels in CsA-exposed groups were significantly higher than untreated groups, but ligation did not affect TGF-beta1 level. These findings suggest that CsA-induced GO can be exacerbated by local inflammation. TGF-beta1 may be a key factor for the development of GO.

The Relationship between Proliferating Cell Nuclear Antigen Expression and Histomorphometrical Alterations in Cyclosporin A-Induced Gingival Overgrowth in Rats

The aim of this study was to investigate the relationship between Proliferating Cell Nuclear Antigen (PCNA) expression and histomorphometrical alterations in cyclosporin A (CsA)-induced gingival overgrowth with or without microbial dental plaque accumulation. Forty male Wistar rats were equally divided into 4 groups; Group I (control); Group II (CsA); Group III (ligature); Group IV (ligature and CsA). After 8 weeks of experimental period, rats were subsequently decapitated and mandibular molars were dissected. Gingival overgrowth was determined by measuring depth of the gingival sulcus, then the mandible were decalcified and serial sections were obtained for histomorphometric and immunohistochemical analysis. Histomorphometric analysis included the measurement of epithelial thickness; immunohistochemical analysis included the assessment of PCNA expression in the oral and sulcular epithelium of buccal and lingual gingiva. Epithelial thickness and PCNA expression were significantly increased in buccal oral epithelium of Group II (p < 0.05) and in all regions in Group IV (p < 0.05) compared to control group. Also gingival overgrowth was more prominent in Group IV in comparison to Group II. These results indicate that CsA-induced gingival alterations are closely associated with increased epithelial proliferative activity, and dental plaque accumulation seems not to be an essential but to be an aggrevating factor for the progression of the lesion.

Increased Expression of Vascular Endothelial Growth Factor in Cyclosporin A‐Induced Gingival Overgrowth in Rats

Gingival overgrowth is a side effect associated with cyclosporin A (CsA) therapy. The lesion is characterized by increased epithelial thickness, enlargement of connective tissue, and increased vascularization. The aim of this experimental study was to examine the role of vascular endothelial growth factor (VEGF) in the pathogenesis of CsA-induced gingival overgrowth. Twenty male Wistar rats were divided into two groups of 10 animals each. For the development of gingival overgrowth, one group received CsA therapy subcutaneously in a daily dose of 10 mg/kg for 60 days, and the other group was used as a control. At the end of the experimental period, rats were subsequently decapitated, and the mandibles with the surrounding gingiva and soft tissue were removed. Half of each sample was used for histomorphometric analysis, and the other half was used for biochemical analysis. Histomorphometric analysis included the measurements of the number and diameter of blood vessel profiles under a microscope, and biochemical analysis included the assessment of VEGF concentration by enzyme-linked immunosorbent assay (ELISA). The histomorphometric findings showed that the number of blood vessel profiles increased in the CsA group compared to the control group (P <0.001), although the increase in the diameter of blood vessel profiles was not significant (P >0.05). The biochemical findings showed that in vivo VEGF expression was higher in the CsA group compared to the control group (P <0.001). The results of this study suggest that increased VEGF expression may be associated with the pathogenesis of CsA-induced gingival overgrowth.

Diltiazem did not induce gingival overgrowth in rats: a clinical, histological and histometric analysis

The administration of calcium channel blockers has been associated with gingival overgrowth. However, there are few studies in humans or animals that evaluated the effect of diltiazem on gingival tissues. The present study assessed the influence of diltiazem, at different dosages and treatment duration, on gingival tissues of rats, using clinical, histological and histometric analyses. Eighty young male rats were separated into eight groups according to the dosage and duration of treatment. Rats were treated for 20 or 40 days with a daily subcutaneous injection of 5, 20 or 50 mg/kg of body weight of diltiazem. The results confirmed that diltiazem did not induce gingival overgrowth in rats. For all animals, the evaluation did not show gingival alterations regardless of the dosages and periods of treatment. The histometric analysis showed no significant change in the area of epithelium and connective tissues, although after 40 days of treatment a decrease in the area of connective tissue was observed, without statistically significant difference from control groups. Within the limits of this study, we suggest that diltiazem did not induce gingival overgrowth.

Establishment of Rat Model of Drug-Induced Gingival Overgrowth Induced by Continuous Administration of Phenytoin

It is well-known that the anticonvulsant drug, phenytoin (PHT), induces gingival overgrowth as a side effect. The mechanism of PHT-induced gingival overgrowth, however, is not well understood. One reason for this is the lack of an adequate animal model for the PHT-induced gingival overgrowth. The purpose of this study was to establish a rat model of the drug-induced gingival overgrowth. Fourteen-day-old rats were randomly divided into 3 groups (5 rats/group). The control rats received only the vehicle. The rats in the experimental group were injected with 50 mg/kg per day (group L) and 100 mg/kg per day (group H) of PHT. They received a subcutaneous injection of vehicle or PHT twice a day for 42 days. A charge-coupled device (CCD) laser displacement sensor was used for measurement of the severity of gingival overgrowth of the mandibles. There was no significant difference in the growth of rats between the PHT-injected and the control groups. The CCD laser displacement sensor can measure minute changes in the gingival overgrowth in rats, and a significant extension of the buccal gingiva was observed in groups L and H. Using the CCD sensor, it is possible to quantify the change in the gingiva under precise control of the PHT dose.

Decreased expression of alpha2 integrin in fibroblasts isolated from cyclosporin A- induced gingival overgrowth in rats.

Cyclosporin A (CsA), an immunosuppressive agent, induces fibrous gingival overgrowth through reduction of collagen phagocytosis by fibroblasts. Distinct receptors are involved in the binding of collagen to fibroblasts in collagen phagocytosis, and alpha2beta1 integrin serves as a specific receptor for type I collagen on fibroblasts. To elucidate the role of alpha2beta1 integrin in CsA-induced gingival overgrowth, we investigated collagen phagocytosis and alpha2beta1 integrin expression in rat gingival fibroblasts. Fibroblats were isolated from gingiva of rats fed a powdered diet containing or lacking CsA for 30 d. Flow cytometric analysis were performed to measure the collagen phagocytosis and the alpha2 integrin expression in fibroblasts. Furthermore, total RNAs were isolated from fibroblasts, and the reverse transcriptase-polymerase chain reaction was employed to investigate the mRNA levels of alpha2 integrin. In vitro collagen phagocytosis assay revealed that CsA-treated and control fibroblasts contained a mean of 13.5% and 36.1% phagocytic cells, respectively. CsA-treated fibroblasts had 28% lower expression of alpha2 integrin than that of control. and mRNA expression of alpha2 integrin in CsA-treated fibroblasts was apparently lower than in the controls, but the mRNA expression of beta1 integrin was not affected. These findings suggest that one etiological factor of gingival overgrowth may be inhibition of collagen phagocytosis by reducing alpha2 integrin expression in gingival fibroblasts.

Cell cycle deregulation in liver lesions of rats with and without genetic predisposition to hepatocarcinogenesis

Preneoplastic and neoplastic hepatocytes undergo c-Myc up-regulation and overgrowth in rats genetically susceptible to hepatocarcinogenesis, but not in resistant rats. Because c-Myc regulates the pRb-E2F pathway, we evaluated cell cycle gene expression in neoplastic nodules and hepatocellular carcinomas (HCCs), induced by initiation/selection (IS) protocols 40 and 70 weeks after diethylnitrosamine treatment, in susceptible Fisher 344 (F344) rats, and resistant Wistar and Brown Norway (BN) rats. No interstrain differences in gene expression occurred in normal liver. Overexpression of c- myc, Cyclins D1, E, and A, and E2F1 genes, at messenger RNA (mRNA) and protein levels, rise in Cyclin D1-CDK4, Cyclin E-CDK2, and E2F1-DP1 complexes, and pRb hyperphosphorylation occurred in nodules and HCCs of F344 rats. Expression of Cdk4, Cdk2, p16 INK4A, and p27 KIP1 did not change. In nodules and/or HCCs of Wistar and BN rats, low or no increases in c- myc, Cyclins D1, E, and A, and E2F1 expression, and Cyclin-CDKs complex formation were associated with p16 INK4A overexpression and pRb hypophosphorylation. In conclusion, these results suggest deregulation of G1 and S phases in liver lesions of susceptible rats and block of G1-S transition in lesions of resistant strains, which explains their low progression capacity. (H EPATOLOGY 2002;35:1341-1350.)

Análise quantitativa dos tecidos gengivais de ratos tratados com fenitoína e ciclosporina

Os aumentos gengivais podem ser decorrentes de reações teciduais a estímulos idiopáticos, patológicos e farmacológicos. O objetivo desse trabalho foi avaliar morfometricamente e estereologicamente a ação da fenitoína (Fen) e ciclosporina (CsA) sobre os tecidos gengivais de ratos. Dez ratos receberam, por via intraperitonial, Fen na dose inicial de 2 mg/kg de peso corporal/dia, aumentando 2 mg a cada duas semanas, durante 60 dias. Em outros 10 ratos, administraram-se, por via subcutânea, 10mg/kg de peso corporal/dia de CsA, durante o mesmo período do grupo anterior. Os valores morfométricos e estereométricos dos tecidos gengivais dos ratos tratados com CsA foram significativamente maiores quando comparado com os valores dos tecidos gengivais do grupo tratado com Fen. Esses resultados sugerem que a CsA na dose utilizada é mais eficaz no desenvolvimento do aumento gengival em ratos, podendo estar atuando na proliferação de fibroblastos e no desequilíbrio fisiológico da síntese de fibras colágenas.

Role of medullasin in nifedipine-induced gingival overgrowth in rats

To clarify the possible pathophysiological role of medullasin, a neutrophil elastase-like proteinase, in nifedipine (NF)-induced gingival overgrowth, a rat model of gingival overgrowth was first established using a diet containing NF. The relation between histopathological changes and the distribution of the proteinase was then investigated. Thirty-two, specific pathogen-free 20 day-old, male, Fisher 344 rats were fed a diet containing NF and killed at 2, 8, 16 and 32 weeks. Control rats ( n=32) were fed the same diet but without the drug. The mandible of each rat was resected and sectioned at 4- μm thickness buccolingually between the first and second molars. Computer image analysis was used to evaluate the extent of overgrowth in the approximal gingiva of each sample. To examine medullasin activity, the mean percentage of medullasin-positive cells per total cells counted in the pocket epithelium and the connective tissue adjacent to the epithelium of approximal gingiva was determined immunohistochemically. The height of the mid-portion and the area in NF-treated group increased significantly with time (with the exception of area at 2 weeks) compared with the corresponding regions in the control group. A marked inflammatory-cell infiltration and elongated rete pegs, especially in the mid-portion of approximal gingiva, were seen in the NF-treated group. The mean percentages of medullasin-positive cells in the NF-treated group at 8, 16 and 32 weeks were significantly higher than those of the control. Although medullasin-positive cells were mainly neutrophils, in several samples of the NF-treated group they were recognized as macrophage-like. These findings suggest that medullasin may be involved in host defence and immunoregulation in a NF-induced rat model of gingival overgrowth.

Nifedipine-induced gingival overgrowth in rats: brief review and experimental study.

The first case report of gingival overgrowth induced by nifedipine (NIF), a calcium-beta blocker, was in 1984. However, the association between gingival alterations and the drug therapy of sodium diphenyl hydantoinate was initially described in 1939. The purpose of the experimental study was to examine the effect of NIF on gingival morphology in an animal model. Forty-five male Sprague-Dawley rats were randomly divided into 3 groups. Animals in each group daily received NIF in dimethyl sulfoxide by gastric feeding at a dosage of 0 (control), 30, or 50 mg/kg body weight for 9 weeks. Gingival gross morphology was assessed tri-weekly from stone models obtained from the mandibular incisal region. Animals were sacrificed at the end of study and tissue blocks were processed for histopathologic and histometric evaluation. Histometric analysis was performed at 5 selected tissue levels. Macro- and microscopic significantly increased gingival dimensions were demonstrated in NIF-treated animals compared to control. Although a fibrovascular tissue was observed in the tooth-gingiva interface for both NIF-treated and control animals, it was thicker and appeared earlier in NIF-treated animals. The results of the present study suggest that gingival overgrowth can be induced by NIF in rats and that the gingival overgrowth appears dose dependent.

The study on the relationship between blood Cyclosporin A level and gingival overgrowth in rats

The study on the relationship between blood Cyclosporin A level and gingival overgrowth in rats

The effect of plaque retention on cyclosporine-induced gingival overgrowth in rats.

The purpose of this study was to examine the role of plaque retention on cyclosporine A (CsA)-induced gingival overgrowth. Forty-five male Sprague-Dawley rats, 15 for each of three CsA dosage conditions, were unilaterally ligated around the first mandibular molar (plaque retention). The silk ligature was left in place for 6 weeks. Contralateral first molars served as unligated controls. The daily dosage of CsA, administered by gastric feeding, was 0, 3, or 10 mg/kg body weight. Stone models from biweekly impressions of the molar sites were used to investigate development of gingival overgrowth. Rats were sacrificed at 6 weeks for histopathological and histometric examination of the molar sites. Gingival overgrowth was significantly increased in sites with higher CsA dosage, longer treatment duration, and ligation. Gingival overgrowth was enhanced in ligated sites regardless of CsA dosage. However, the odds ratio of ligated over unligated sites for gingival overgrowth increased with increasing CsA dosage. The histopathological and histometric examination revealed significantly increased gingival volume in ligated sites in CsA-treated animals. The tissue enlargement included both the epithelium and the connective tissue; however, the epithelium to connective tissue ratio remained unaltered. Within limitations of the study, we suggest that plaque retention magnifies CsA-induced gingival overgrowth; thus, dental plaque appears to be a cofactor in the development of CsA-induced gingival overgrowth.