n-phenacylthiazolium-bromide and Disease-Models--Animal

Topics: Animals; Diabetic Angiopathies; Disease Models, Animal; Drug Design; Glycation End Products, Advanced; Guanidines; Humans; Hypoglycemic Agents; Thiadiazoles; Thiazoles; Thiazolidines

This study aimed to develop pH-responsive polylactide-glycolic acid co-polymer and chitosan (PLGA/chitosan) nanosphere as an inflammation-responsive vehicle and evaluate the potential of the nanosphere encapsulating metronidazole, an antibiotic, and N-phenacylthiazolium bromide (PTB), a host modulator, for treating periodontitis.. PLGA/chitosan nanospheres were fabricated using oil-in-water emulsion method. Experimental periodontitis was induced on the rat maxillae, and the sites were randomly allocated to four treatment categories, including periodontitis alone (PR), periodontitis with nanospheres alone, nanospheres encapsulating metronidazole (MT) and nanospheres encapsulating PTB (PB). The ligature was retained until the animals were killed, and the treatment outcome was evaluated by the progression of periodontal bone loss (PPBL), inflammatory cell infiltration and collagen deposition.. The encapsulated drug was released rapidly from the nanospheres without significant initial burst release at pH 5.5. Compared with group PR, PPBL was significantly reduced in groups MT and PB on day 4 (P<.05). On day 21, PPBL was significantly lower in group PB (P<.05). In groups MT and PB, inflammation was significantly reduced in groups MT and PB relative to groups PR and periodontitis with nanospheres alone (P<.05), and collagen deposition was significantly greater relative to group PR (P<.05).. PLGA/chitosan nanospheres encapsulating metronidazole or PTB showed potential for modulating periodontitis progression.

Topics: Animals; Anti-Infective Agents; Chitosan; Disease Models, Animal; Disease Progression; Lactic Acid; Metronidazole; Nanospheres; Periodontitis; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats, Sprague-Dawley; Thiazoles

Blockade of advanced glycation end-products (AGE) is able to reduce diabetic complications and control periodontitis. This study aimed to determine whether the application of aminoguanidine (AG), an AGE inhibitor, or N-phenacylthiazolium bromide (PTB), an AGE breaker, facilitates the healing of an osseous wound in non-diabetic animals.. 2.6 mm diameter full-thickness osseous wounds were created bilaterally in 54 healthy Sprague-Dawley rats. Rats received daily normal saline, AG, or PTB injections respectively and were euthanized after 7 days, 14 days, or 28 days (n = 6). The wound healing pattern was assessed by micro-computed tomography, histology, histochemistry for the fiber arrangement, and the gene expression levels of AGE receptor, tumor necrosis factor-α, type I collagen, and fibronectin.. Under the AG and PTB administration, osteogenesis was apparently promoted in the early stages of healing, but the union of the osseous wound and the fibril re-arrangement was apparently retarded. No significant difference was found in any of the micro-computed tomography parameters as compared to the control in the first 14 days, whereas the relative bone volume was significantly higher in the control at Day 28. AGE receptor and tumor necrosis factor-α were depressed in the PTB group, but only temporarily at Day 14 in the AG group. Therefore, at Day 14, type I collagen was significantly upregulated in the PTB group, and fibronectin was significantly increased in the AG group.. Anti-AGE agents reduced inflammation but did not apparently facilitate osteogenesis during the osseous wound repair.

Topics: Animals; Collagen Type I; Disease Models, Animal; Fibronectins; Glycation End Products, Advanced; Guanidines; Male; Mandibular Injuries; Rats; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Thiazoles; Tumor Necrosis Factor-alpha; Wound Healing; X-Ray Microtomography

Advanced glycation end products (AGEs) are involved in the inflammatory process and are considered to be etiologic factors of diabetic periodontitis. The purpose of this study is to investigate the capability of N-phenacylthiazolium bromide (PTB), a glycated cross-link breaker, in the modulation of periodontitis in various disease phases.. Mitogenesis and cytotoxicity of human periodontal ligament cells (hPDLCs) undergoing PTB treatment were evaluated in vitro. In vivo biomodulation was investigated by systemically administering PTB in the induction, progression, and recovery phases of ligature-induced periodontitis in rats, with the results evaluated by microcomputed tomography, histology, immunohistochemistry of the AGE and AGE receptor (RAGE), and gene expression of tumor necrosis factor-α (TNF-α), RAGE, periostin, fibronectin, and type I collagen.. Significantly promoted mitogenesis and reduced cytotoxicity of hPDLCs were noted with 0.05 to 0.1 mM PTB treatment at 24 hours. Systemic PTB administration significantly reduced periodontal bone loss, AGE deposition, and expressions of TNF-α and RAGE but elevated the periostin level in all three phases of periodontitis.. PTB inhibits the induction and progression of periodontitis and facilitates its recovery via improving cellular viability and inhibiting the AGE-RAGE axis.

Topics: Alveolar Bone Loss; Animals; Blood Glucose; Cell Adhesion Molecules; Cell Culture Techniques; Cell Line; Cell Survival; Collagen Type I; Disease Models, Animal; Disease Progression; Fibronectins; Glycated Hemoglobin; Glycation End Products, Advanced; Humans; Immunohistochemistry; Male; Periodontal Ligament; Periodontitis; Rats; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Thiazoles; Tumor Necrosis Factor-alpha