Does nifedipine aggravate cyclosporin--induced gingival overgrowth? An experiment in rats

BACKGROUND: Nifedipine (NIF) may aggravate cyclosporin A (CsA)-induced gingival overgrowth because the potentiated gingival overgrowth has been observed in the patients treated with CsA and NIF. The purpose of this study was to evaluate whether NIF could aggravate the CsA-induced gingival overgrowth in a rat model. METHODS: Ninety male Sprague-Dawley rats were divided into 6 groups: the first group received 8 mg/kg of CsA daily by gastric feeding for 6 weeks; the second and third groups received NIF daily at a dosage of 10 or 50 mg/kg; the fourth and fifth groups received CsA (8 mg/kg) and NIF (10 or 50 mg/kg); and the sixth group received solvents as a negative control. Gingival dimensions (including bucco-lingual depth, mesio-distal width, and vertical height) were assessed bi-weekly from impressed stone models of the mandibular incisal region. At the end of the experiment, the animals were sacrificed. Following histopathological procedures, serial horizontal sections were obtained at the base of the central incisal papilla. Two tissue levels were selected for histometric analysis. Level 1 was defined as the point where the lingual gingiva embraced the bucco-lingual midpoint of the roots and the level 2 as the point where the lingual gingiva at the enamel-dentinal junction approximated the bucco-proximal angle of the roots. The bucco-lingual depth and the mesio-distal width of the papilla were recorded on 5 consecutive sections at the 2 levels, respectively. RESULTS: At the 6-week observations, the gingival dimensions (including the depth, width, and height) significantly increased after CsA therapy and the increasing treatment duration; however, only the mesio-distal width increased after NIF therapy. For NIF therapy alone, a positive linear relation was noted by increased NIF treatment dosages in all gingival dimensions at week 6. But, this relationship was not found in the combined therapies. By histometry, tissue dimensions increased following single drug therapy, either CsA or NIF, at both levels. In animals with the combined therapies, the tissue dimensions decreased if the animals received 10 mg NIF, while they rebounded to control levels with the 50 mg dosage. A dose-dependent positive pattern by NIF was noted in tissue dimensions, but the pattern did not occur in animals that received combined therapy. CONCLUSIONS: The gingival dimensions increased after CsA or NIF therapy, although they were more prevalent with CsA. But the augmenting pattern in gingival morphology observed with CsA therapy decreased when the animals received additional NIF. Therefore, we question whether NIF is a critical factor in aggravating the CsA-induced gingival overgrowth.     

Morphological evaluation of combined effects of cyclosporin and nifedipine on gingival overgrowth in rats

It has previously been shown that, while cyclosporin A (CsA) and nifedipine both cause gingival overgrowth in the rat, the combined use of these drugs increases the severity of overgrowth. The aim of this study was to describe the histometry and densities of fibroblasts, collagen fibers and vessels in the gingival tissue of rats that were treated with CsA and nifedipine, either alone or in combination. Rats were treated for 60 days with a daily subcutaneous injection of 10 mg/kg body weight of CsA and/or with 50 mg/kg body weight of nifedipine added to the chow. The results confirmed that CsA causes a more severe overgrowth than nifedipine, and that the combined use of these drugs increases the overgrowth severity. All the rat groups that were studied showed that, as the severity of overgrowth increased, there was a parallel increase in fibroblasts and collagen, and a decrease in vessel content. Therefore, independently of whether the gingival overgrowth was caused by CsA alone, nifedipine alone, or both treatments in combination, the fibroblast and collagen density increased in parallel with the severity of the overgrowth.     

Effect of cyclosporin A on alveolar bone homeostasis in a rat periodontitis model

OBJECTIVES: The administration of cyclosporin A has been associated with significant bone loss and increased bone remodeling. The present investigation was designed to evaluate the effects of cyclosporin A on alveolar bone of rats subjected to experimental periodontitis, using serum, stereometric and radiographic analysis. METHODS: Twenty-four rats were divided into one of the following groups with six animals each: group I, control rats; group II, in which the animals received a cotton ligature around the lower first molars; group III, in which the rats received a cotton ligature around the lower first molars and were treated with 10 mg/(kg body weight day) of cyclosporin A; group IV, in which the rats were treated with 10 mg/(kg body weight day) of cyclosporin A. At the end of experimental period, at 30 days, animals were killed and the serum calcium and alkaline phosphatase levels were measured in all groups. The distance from the alveolar bone crest to the cemento-enamel junction was measured radiographically for each mesial surface of the lower first molars of each rat. After histological processing, the stereological parameters: volume densities of multinucleated osteoclasts (V(o)), alveolar bone (V(b)), marrow (V(m)), and relation of eroded surface/bone surface (Es/Bs) were assessed at the mesial region of the alveolar bone. RESULTS: Significant decreases in serum calcium were observed in those groups that received cyclosporin A therapy. No significant changes in serum alkaline phosphatase were observed. The therapy with cyclosporin A combined with the ligature placement decreased the V(b) and increased the V(o), V(m) and Es/Bs at the mesial surface of lower first molars. On the other hand, the radiographic data showed that cyclosporin A therapy diminished the alveolar bone loss at the mesial surface of the lower first molars. CONCLUSIONS: Therefore, within the limits of this study, we suggest that cyclosporin A at immunosuppressive levels can bring about an imbalance in the alveolar bone homeostasis in rats. However, in the presence of inflammatory stimulation, the inhibition of the immune system by cyclosporin A may decrease the initial periodontal breakdown.     

Combined effects of cyclosporin and nifedipine on gingival overgrowth in rats is not age dependent

BACKGROUND: Cyclosporin A and nifedipine cause gingival overgrowth in rat, and the combined use of these drugs increases the overgrowth severity. OBJECTIVE: The purpose of this study was to compare gingival overgrowth of rats of differents ages treated with cyclosporin A and nifedipine alone or given concurrently. MATERIALS AND METHODS: Rats 15, 30, 60 and 90 d old were treated with 10 mg/kg body weight of cyclosporin A and/or 50 mg/kg body weight of nifedipine in the chow. RESULTS: Young rats showed evident gingival overgrowth with nifedipine, cyclosporin A, and cyclosporin A and nifedipine given concurrently. Adult rats did not show significant gingival alterations when treated with cyclosporin A and nifedipine alone. Nevertheless evident gingival overgrowth with alterations of the epithelium and connective tissue were observed when treated simultaneously with cyclosporin A and nifedipine. CONCLUSION: These results suggest that the combined effects of cyclosporin A and nifedipine on gingival overgrowth in rat is not age dependent.     

Cyclosporin-induced gingival overgrowth at the newly formed edentulous ridge in rats: a morphological and histometric evaluation

BACKGROUND: Since cyclosporin A (CsA)-induced overgrowth seldom occurs at sites distant from teeth, the periodontal ligament has been considered significant. The aim of this study was to examine overgrowth occurrence at the edentulous ridge--the sites without the ligament--after CsA therapy in rats. METHODS: After extracting all right maxillary molars, 16 Sprague-Dawley rats underwent a 2-week healing period. The animals were separated into CsA and control groups. CsA rats received 15 mg/kg of CsA by gastric feeding for 4 weeks, while the control group received only mineral oil. At the end of study, all animals were sacrificed and stone models were immediately obtained by rubber-based impressions. The edentulous ridge morphology, including the bucco-lingual width and the vertical height, was measured on the models. For histometry, 10 sections were selected from the edentulous ridge of each animal after undecalcified tissue preparation. The soft tissue areas of the edentulous ridge and the trabecular bone morphology of the dental alveolus were measured. RESULTS: CsA therapy produced a significant increase of the ridge width and height, measured from the stone models, when compared to the control group. Under histometry, CsA resulted in a significant increase of the epithelium, connective tissue, and total soft tissue areas. The measured trabecular bone volume was affected by both examining factors: the drug therapy and the location of the dental alveolus. CsA therapy produced a significant loss of bone volume but a significant increase of the bone-specific surface area. Although the mean osteoid volume was similar between CsA and control groups, a significant decrease of the fractional formation surface in the CsA group was revealed. CONCLUSIONS: An enlarged edentulous ridge and an altered dental alveolar bone morphology were observed in CsA-treated animals at the end of the study; therefore, we suggest that CsA may induce not only a soft tissue overgrowth but also an alveolar bone alteration at the edentulous ridge. The hypothesis that tooth or periodontal ligament is an essential component for the overgrowth development is questioned.     

Effects of long-term cyclosporin therapy on the periodontium of rats

BACKGROUND: The treatment of cyclosporin A triggers an early bone loss and gingival overgrowth. There is a lack of studies exploring the effects of long-term cyclosporin A therapy on alveolar bone homeostasis and gingival tissue. OBJECTIVE: The purpose of this study was to evaluate the effects of long-term therapy with cyclosporin A on the gingival tissue and on the alveolar bone metabolism in rats. MATERIALS AND METHODS: Rats were treated for 60, 120, 180 and 240 days with a daily subcutaneous injection of 10 mg/kg body weight of cyclosporin A. At the end of experimental periods, animals were killed and the serum calcium (Ca(2+)) and alkaline phosphatase levels were measured in all groups. After histological processing, the oral epithelium and the connective tissue, as well as volume densities of alveolar bone (V(b)) and multinucleated osteoclasts (V(o)), were assessed at the region of the lower first molars. RESULTS: Significant increases in the serum alkaline phosphatase were observed in those groups that received cyclosporin A therapy. After 60 and 120 days of the treatment with cyclosporin A, evident gingival overgrowth associated with a significant increase of epithelium and connective tissue was observed, as well as a decrease of the densities of bone and an increase of densities of osteoclasts. After 180 and 240 days of the treatment, there was a reduction of the gingival overgrowth associated with significant decreases of epithelium and connective tissue, as well as an increase of bone densities and a decrease of osteoclasts. CONCLUSION: Within the limits of this experimental study, it can be concluded that the deleterious periodontal effects of cyclosporin A administration may be time-related side-effects.     

Simvastatin therapy in cyclosporine A-induced alveolar bone loss in rats

Background and Objective:  Cyclosporine A treatment is important in the therapy of a number of medical conditions; however, alveolar bone loss is an important negative side-effect of this drug. As such, we evaluated whether concomitant administration of simvastatin would minimize cyclosporine A-associated alveolar bone loss in rats subjected, or not, to experimental periodontal disease.
Material and Methods:  Groups of 10 rats each were treated with cyclosporine A (10 mg/kg/day), simvastatin (20 mg/kg/day), cyclosporine A and simvastatin concurrently (cyclosporine A/simvastatin) or vehicle for 30 days. Four other groups of 10 rats each received a cotton ligature around the lower first molar and were treated similarly with cyclosporine A, simvastatin, cyclosporine A/simvastatin or vehicle. Calcium (Ca²⁺), phosphorus and alkaline phosphatase levels were evaluated in serum. Expression levels of interleukin-1β, prostaglandin E₂ and inducible nitric oxide synthase were evaluated in the gingivomucosal tissues. Bone volume and numbers of osteoblasts and osteoclasts were also analyzed.
Results:  Treatment with cyclosporine A in rats, with or without ligature, was associated with bone loss, represented by a lower bone volume and an increase in the number of osteoclasts. Treatment with cyclosporine A was associated with bone resorption, whereas simvastatin treatment improved cyclosporine A-associated alveolar bone loss in all parameters studied. In addition, simvastatin, in the presence of inflammation, can act as an anti-inflammatory agent.
Conclusion:  This study shows that simvastatin therapy leads to a reversal of the cyclosporine A-induced bone loss, which may be mediated by downregulation of interleukin-1β and prostaglandin E₂ production.     

环孢素A联合牙龈卟啉单胞菌脂多糖局部应用对大鼠牙周组织缺损修复影响研究

目的    探讨环孢素A（CsA）联合牙龈卟啉单胞菌脂多糖（P.g-LPS）局部应用对大鼠牙周组织缺损修复的影响。方法    　成功构建18只SD大鼠牙周急性缺损模型,随机均分为3组,分别在缺损对应口腔内局部注射生理盐水（对照组）、CsA 2 mg/kg（CsA组）或CsA 2 mg/kg+P.g-LPS 1μg （CsA+P.g-LPS组）,30 d后处死全部大鼠,切取双侧下颌骨制作标本切片,HE染色观察CsA单独应用及与低剂量P.g-LPS联合应用对大鼠牙周组织缺损修复的影响。结果    CsA 2 mg/kg单独及与低剂量P.g-LPS联合应用,对大鼠牙周组织缺损的修复均有一定促进作用,但与对照组相比,差异均无统计学意义（P > 0.05）。结论    在模拟人体牙周炎恢复期低毒素、微炎症状态的牙周情况下局部应用CsA,既不会促进微炎症状态下的缺损修复,也不会与微炎症表现出协同作用而导致牙周组织的损害。     

Effect of high-density lipoprotein on lipopolysaccharide-induced alveolar bone resorption in rats

OBJECTIVE: To determine whether treatments with high-density lipoprotein (HDL) may alter the lipopolysaccharide (LPS)-induced alveolar bone resorption in rats. MATERIALS AND METHODS: Rats were injected with 500 microg of LPS from Escherichia coli at the alveolar mucosa of lower right first molar once every 2 days for 8 days. The negative and positive control were injected with phosphate buffered saline (PBS) and LPS alone, respectively. In HDL-treated animals various concentration of HDL were injected immediately before, after the third or the final LPS injection. The bone sections were stained with tartrate-resistant acid phosphatase (TRAP) and the numbers of both osteoclasts and preosteoclasts and the levels of alveolar bone resorption were assessed. RESULTS: The numbers of both osteoclasts and preosteoclasts and the levels of alveolar bone resorption in animals treated with HDL before or during LPS injections were lower than those in the positive control, but higher than those in the negative control, regardless of HDL doses. Similar results were also observed in animals treated with 250 and 500 microg of HDL after the final LPS injection. Only treatments with 1000 microg of HDL after LPS injections completely reduced the number of both osteoclasts and preosteoclasts, but only partially decreased the alveolar bone resorption. CONCLUSION: HDL treatments partially reduced the LPS-induced alveolar bone resorption in vivo in rats, suggesting that HDL may neutralize the ability of LPS to induce alveolar bone resorption.     

������A��������߲��������֬���Ǿֲ�Ӧ�öԴ���������֯ȱ���޸�Ӱ���о�

??Objective    To evaluate the effects of cyclosporine A??CsA??and Porphyromonas gingivalis-lipopolysaccharide??P.g-LPS??on defect repair in mandibular tissue in rats. Methods    Saline??CsA??2mg/kg????CsA??2mg/kg??+P.g-LPS??1μg??were injected into the periodontal defects in Sprague Dawley rats. Thirty days after injection??animals were sacrificed??the formation of newly formed alveolar bone??cementum and the width of periodontal ligament were analyzed histomorphometrically. Results    2 mg/kg of CsA??used singly or in combination with low-dose P.g-LPS??had a certain effects on the regeneration of the periodontal tissue in Sprague Dawley rats??but the difference was not statistically significant compared with the control group. Conclusion    The local application of CsA under the condition of low toxin and microinflammatory symptoms??during the recovery period of periodontitis??will not promote the repair of defects in the condition of microinflammation??nor will cooperate with microinflammation and cause damage to periodontal tissue.     

Impact of streptozotocin-induced diabetes on rat blood and alveolar bone affected by occlusal stress

Abstract – Adult male and female rats were used as test animals. The experimental diabetes, mellitus was provoked with one dose of i.v. injection of streptozotocin (65 mg/kg body weight), which interferes with the insulin release mechanism in pancreatic β cells. After a follow-up period of 10 wk an average loss of 10% of body weight and an increase of 25% in the amount of blood obtained by decapitation was recorded in the test animals. The biochemical assays performed on the serum of the diabetic rats showed, for both sexes, a fourfold rise in the plasma glucose level, a threefold rise in plasma alkaline phosphatase activity and plasma alanine transferase activity as well as a 1.5-fold rise in plasma creatine value. The two latter values indicated systematic disorders reflected in the liver and the kidneys. An increase in serum total calcium and hydroxyproline values was also detected. The clinical studies of the gingiva showed diminished tissue resistance in diabetic rats. The histologic studies of alveolar bone revealed retarded formation of bone matrix and new bone in diabetic animals. However, the stimulated metabolism in alveolar bone, due to the artificially induced stress, increased marginal bone cell activity in both the diabetic and the control group, resulting in increased crestal resorption in the former group. The differences in tissue response observed among the diabetic animals affected and unaffected by stress originated from the disturbed recovering mechanism typically found in diabetic animals.     

Impact of streptozotocin-induced diabetes on rat blood and alveolar bone affected by occlusal stress

Adult male and female rats were used as test animals. The experimental diabetes mellitus was provoked with one dose of i.v. injection of streptozotocin (65 mg/kg body weight), which interferes with the insulin release mechanism in pancreatic beta cells. After a follow-up period of 10 wk an average loss of 10% of body weight and an increase of 25% in the amount of blood obtained by decapitation was recorded in the test animals. The biochemical assays performed on the serum of the diabetic rats showed, for both sexes, a fourfold rise in the plasma glucose level, a threefold rise in plasma alkaline phosphatase activity and plasma alanine transferase activity as well as a 1.5-fold rise in plasma creatine value. The two latter values indicated systematic disorders reflected in the liver and the kidneys. An increase in serum total calcium and hydroxyproline values was also detected. The clinical studies of the gingiva showed diminished tissue resistance in diabetic rats. The histologic studies of alveolar bone revealed retarded formation of bone matrix and new bone in diabetic animals. However, the stimulated metabolism in alveolar bone, due to the artificially induced stress, increased marginal bone cell activity in both the diabetic and the control group, resulting in increased crestal resorption in the former group. The differences in tissue response observed among the diabetic animals affected and unaffected by stress originated from the disturbed recovering mechanism typically found in diabetic animals.     

Cyclosporin A-induced alterations of dentinogenesis in rat molars

Cyclosporin A (CsA), a widely used immunosuppressive drug, induces gingival overgrowth and modifications of bone remodelling. The scope of this study was to investigate the possible effect of CsA on dentin. Thirty mg/kg/day of CsA were administered orally to male Sprague-Dawley rats for nineteen weeks. The same number of control rats received oil-based vehicle solution. Rats were anesthetized, and tissues were fixed by an intracardiac perfusion of fixative solution. Mandibles were dissected, demineralized, and processed for Epon embedding, Semi-thin sections of the first molars revealed alterations at the secondary dentin-pulp interface in four out of six experimental animals. The changes consisted of the formation of: 1) osteodentin spurs, in which the volume and interface with the secondary dentin varied from about 25,000 to 75.000 μm³ and from 1400 to 3530 μm², respectively; 2) abnormally shaped and irregularly spaced incremental lines; and 3) numerous globular formations embedded in dentin or free in the pulp. These results indicate that CsA induces abnormal mineralized matrix formation in dentin and in the peripheral part of the pulp in rat molars.     

The effect of alendronate on resorption of the alveolar bone following tooth extraction

Maintenance of alveolar bone width and height following tooth loss is essential with regard to the restoration of missing teeth with endosseous dental implants or prosthodontics approaches. A various amount of alveolar ridge resorption is likely to occur after tooth extraction at the buccal and lingual alveolar bone plates. Bisphosphonates, alendronate, is well known for its potent inhibition of osteoclast-mediated bone resorption. The objective of this study was to examine the inhibitory effect of alendronate on alveolar bone resorption following tooth extraction in rats. Male Wistar Albino rats were divided into three groups: baseline group, saline-treated group and alendronate-treated group. The saline-treated group was administered with daily saline solution for 2 and 4 weeks respectively while the alendronate-treated group was given a daily amount of 0.25 mg/kg alendronate subcutaneously for the same periods. The level of urinary calcium, creatinine, and serum calcium, alkaline phosphatase and phosphate were measured. Serum alkaline phosphatase level was measured as a marker of osteoblastic activity. Histopathological sections of 4 microm thickness were obtained from the right first mandibular molar region in a bucco-lingual direction. The number of osteoclasts, osteoblasts, and haversian canals, the number and size of resorptive lacunae, and osteoid formation were evaluated histopathologically. The mean thickness of buccal and lingual alveolar bone was measured. In the alendronate-treated group, both buccal and lingual alveolar bone volume reduction was significantly less than the saline treated group. Significant reduction in serum and urinary calcium levels and the number of osteoclasts revealed the pronounced suppression of bone resorption in the alendronate-treated group.     

Therapeutic Effects of Systemic Vitamin K2 and Vitamin D3 on Gingival Inflammation and Alveolar Bone in Rats With Experimentally Induced Periodontitis

Background: The synergistic effects of vitamin D3 and vitamin K2 on bone loss prevention have been reported. This study evaluates the effects of vitamin D3 and vitamin K2 supplementation in conjunction with conventional periodontal therapy (scaling and root planing [SRP]) on gingival interleukin (IL)‐1β and IL‐10, serum bone alkaline phosphatase (B‐ALP) and tartrate‐resistant acid phosphatase 5b (TRAP‐5b), and calcium and alveolar bone levels in rats with experimentally induced periodontitis. Methods: Seventy‐two rats were divided into the following groups: 1) healthy; 2) periodontitis; 3) SRP; 4) SRP + vitamin D3; 5) SRP + vitamin K2; and 6) SRP + vitamins K2 and D3. Periodontitis was induced by ligature placement for 7 days, and vitamin K2 (30 mg/kg) and/or vitamin D3 (2 μg/kg) were administered for 10 days in the SRP + vitamin D3, SRP + vitamin K2, and SRP + vitamins K2 and D3 groups by oral gavage. On day 18, the animals were sacrificed, serum B‐ALP, TRAP‐5b, and calcium levels were measured, gingiva specimens were extracted for IL‐1β and IL‐10 analysis, and distances between the cemento‐enamel junction and alveolar bone crest were evaluated. Results: Alveolar bone levels in the periodontitis group were significantly greater than those in the other five groups. No significant differences were found in gingival IL‐1β and IL‐10, serum B‐ALP and TRAP‐5b, and calcium and alveolar bone levels between the groups receiving SRP and vitamins and the group receiving SRP alone. Conclusion: Within the limitations of this study, vitamin D3 and K2 alone or in combination did not affect gingival IL‐1β and IL‐10, serum B‐ALP and TRAP‐5b levels, or alveolar bone compared with conventional periodontal therapy alone.     

Effects of cyclosporin-A-induced immunosuppression on periapical lesions in rats

Cyclosporin A (CsA) might induce immune response alterations in periapical lesions and modify bone remodeling. This study determined the changes that occur in the periapical lesions of rats during CsA administration and after CsA withdrawal. After the induction of periapical lesions, the animals were treated with CsA (0-20 mg/kg/day) for 4 wks. Lesion volumes were measured by computed tomography. Histological observations and immunohistochemical evaluations were performed with anti-CD3 and anti-CD25 antibodies. CsA administration reduced lesion volumes, and the lesions significantly expanded after CsA withdrawal. CsA inhibited the proliferation and activation of T-cells at lesion sites. The effects of CsA on T-cells were dose-dependent up to 10 mg/kg/day, after which no significant difference was evident. These results suggest that CsA inhibits periapical destruction by interfering with T-cell function in periapical lesions.     

Effects of combined oral treatments with cyclosporine A and nifedipine or diltiazem on drug-induced gingival overgrowth in rats

BACKGROUND: Cyclosporine A (CsA) and calcium channel blockers induce gingival overgrowth in humans and animals. Recently, nifedipine and diltiazem have often been used to control CsA-related hypertension in organ transplant patients. The purpose of this study was to examine the effects of a combined oral treatment of CsA and nifedipine or diltiazem on the severity of gingival overgrowth in rats. METHODS: Fifteen-day-old Fischer rats were treated orally with single or combined applications of CsA, nifedipine, and/or diltiazem for 40 days; and induced gingival overgrowth, rat growth, and blood drug levels were compared among the different experimental groups. The experiment consisted of 6 groups: one control group (group A) and 5 test groups treated with CsA (group B), nifedipine (group C), and diltiazem (group D), as well as those concurrently treated with CsA and nifedipine (group E), and CsA and diltiazem (group F). Gingival overgrowth was determined by measuring the depth of the gingival sulcus. RESULTS: The mandibular buccal gingival sulcus depth of group A was 365 +/- 41.2 microm. Among the test groups, the most remarkable gingival overgrowth was seen in group E (1,020 +/- 63.3 microm), followed by group F (895 +/- 43.8 microm), group B (870 +/- 48.3 microm), group C (525 +/- 116 microm), and then group D (505 +/- 83.2 microm). Rat body weight gain was reduced significantly by oral CsA treatment. Neither nifedipine nor diltiazem suppressed rat growth when used independently; however, rat growth reduced by CsA was further suppressed by a combined use of diltiazem, but not nifedipine. CsA blood levels were reduced by concurrent oral treatment with nifedipine or diltiazem along with the blood levels of those calcium channel blockers when treatment was in combination with CsA. CONCLUSIONS: These results suggest that gingival overgrowth is induced in rats as a side effect of CsA, nifedipine, or diltiazem, and the combined use of these drugs influences rat growth, blood drug levels, and the severity of gingival overgrowth.     

Comparison of the effects of ethane-1-hydroxy-1,1-diphosphonate and dichloromethylene diphosphonate upon periodontal bone resorption in rice rats (Oryzomys palustris).

Young male rice rats maintained on a powdered diet were treated for 10 days with either ethane-1-hydroxy-1,1-diphosphonate (EHDP) or dichloromethylene diphosphonate (Cl₂MDP) at a dose of 4 mg/kg body weight. Cl₂MDP-recipients displayed significantly less alveolar bone loss than EHDP-recipients (p < 0.05) or control animals (p < 0.01) when examined 2 weeks after the treatment.     

Effects of low-dose cyclosporin on osteogenesis of human demineralized bone grafts in a surgically created mandibular defect in rats

BACKGROUND: Demineralized freeze-dried bone matrix (DFDBM) stimulates new bone formation; however, immune reactions from the residual antigens of prepared grafts might play a role in inducing osteogenesis. This study examined whether cyclosporine-A (CsA), an immunosuppressant, enhanced the DFDBM-induced new bone formation. METHODS: After creating a bony defect in the posterior mandible, 40 male Sprague-Dawley rats were divided into four groups of 10 each: no graft with mineral oil (control); no graft with CsA in mineral oil; DFDBM with mineral oil; and DFDBM with CsA in mineral oil (combined therapy). CsA was administered at 2 mg/kg body weight. Five rats in each group were sacrificed at days 10 and 28 and tissue samples were taken for histological examination. RESULTS: Soft tissue was observed in the defects of all animals without grafts, whereas the repaired hard tissue formed in the defects of animals with grafts. Histometery, which was performed only at day 10, revealed both DFDBM and CsA therapies produced a significant increase in the total area of repaired hard tissue. Only CsA therapy significantly increased the new bone area. Compared with the DFDBM group, the composition of the repaired hard tissue in the combined therapy group shifted; i.e., the new bone area increased but the residual particle area decreased. The cartilage formation was greater in the combined therapy group than the DFDBM group. CONCLUSION: Within the limitations of this study, we suggest that the DFDBM grafts play a major role, which could be enhanced by CsA, in the induction of new bone formation, especially at an early phase.     

Cyclosporin A-induced new cementum formation: a morphometric evaluation in the periapical region of rats

Cyclosporin A (CsA) is a potent immunosuppressor used in organ transplantation and in the management of various autoimmune diseases. Recent studies have shown that CsA stimulates deposition of cementum on root surfaces. The aim of this study was to evaluate the periapical cementum thickness and the apical foramen width in CsA-treated rats. Rats weighing 50 g were treated with a daily injection of 10 mg/kg body weight of CsA in the chow for 60 days. The cementum of the mandibular 1st molars was histologically and morphometricaly examined by analysis of 5-microm-thick serial buccolingual paraffin sections stained with hematoxylin and eosin. Histometric and stereologic analyses revealed the presence of large amounts of cementum in all root surfaces, particularly abundant in the periapical region and obliterating the foramen. The volume density of cementoblasts did not increase. Five to 90 days after the termination of CsA therapy, there was no reduction of cementum thickness. These results suggest that cementum deposition is not reversible after cessation of CsA treatment.