Melatonin pretreatment modulates anti-inflammatory, antioxidant, YKL-40, and matrix metalloproteinases in endotoxemic rat lung tissue.

We aimed to investigate the effects of melatonin administered before and during endotoxemia on the lung tissue of rats, cytokine, YKL-40, matrix metalloproteinase (MMP) and inhibitor levels, oxidative stress parameters, and energy balance. Sepsis was induced with lipopolysaccharide (LPS), the cell wall molecule of gram negative bacteria. Rats were divided into four groups, Control, LPS (Escherichia coli O127:B8, 20 mg/kg), melatonin (10 mg/kg), and melatonin+LPS (M+LPS). After injections, lung tissues samples were taken for experimental analyses. YKL-40, thiobarbituric acid reactive substances (TBARS), glutathione reductase (GR), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) enzymes levels were measured, high-energy components were analyzed; tumor necrosis factor-alpha (TNF-α), MMP-2, YKL-40, MMP-9, myeloperoxidase (MPO), tissue inhibitors of matrix metalloproteinase (TIMP)-1, and interleukin (IL)-10 immunoreactivities were investigated. In LPS group, YKL-40, creatine phosphate (both, p < 0.05), SOD, GR, adenosine mono-phophate (AMP), adenosine tri-phosphate (ATP) (for all, p < 0.01) were significantly decreased, while TBARS and adenosine di-phosphate (ADP) levels were increased (p < 0.01, p < 0.05; respectively) compared to other groups. MMP-2 and -9, TIMP-1, TNF-α, IL-10, and MPO immunoreactivity were investigated in LPS group. On the contrary, in M+LPS group, MMP-9, TIMP-1 immunoreactivities were not found and IL-10 and MMP-2 immunoreactivities were found with little involvement. In M+LPS group, YKL-40, GR, AMP, ATP, creatine phosphate (for all, p < 0.05), and SOD (p < 0.01) levels were significantly increased and TBARS levels were decreased (p < 0.05). In our study, we suggest that melatonin exerts a protective and curative effect by reducing the matrix metalloproteinase levels responsible for tissue damage balance, stimulating the release of antioxidant enzymes, regulating cytokines and energy balance during endotoxemia.

Pathological changes and immunoexpression of p63 gene in dental follicles of asymptomatic impacted lower third molars: an immunohistochemical study.

OBJECTIVE: The aim of this study was to examine the pathologic changes and immunoexpressivity of p63 gene in dental follicles (DFs) of asymptomatic partially and completely impacted lower third molars. STUDY DESIGN: Clinical and radiologic examinations included 50 DFs with no signs of abnormal radiolucency (follicular space <2.5 mm), taken from 50 patients. RESULTS: Histopathologic examinations of the specimens revealed 47 normal dental follicular tissues, 1 ameloblastoma, and 2 dentigerous cysts. p63 Immunoexpressivity was stronger in the DFs of the group with completely impacted teeth (64%),than it was in the case of DFs of the group with partially impacted teeth (40%). CONCLUSIONS: Stronger p63 gene immunoexpression in the group with completely impacted teeth might be a consequence of bigger number of stem cells than it is in the case of the group with partially impacted teeth. This study also supports prophylactic removal of impacted teeth because of the development of pathologies associated with them.

Expressions of bax, bcl-2 and Ki-67 in odontogenic keratocysts (Keratocystic Odontogenic Tumor) in comparison with ameloblastomas and radicular cysts.

OBJECTIVE: The aim of the study was to determine the apoptotic features and proliferation potential of odontogenic keratocysts compared with ameloblastomas and radicular cysts by analysing the role of bax, bcl-2, and Ki-67. MATERIAL AND METHOD: The study material consisted of 20 odontogenic keratocysts, 20 radicular cysts, and 20 ameloblastomas. Immunohistochemically, bax, bcl-2 and Ki-67 were applied. The positive cells were evaluated in both neoplastic/nonneoplastic odontogenic epithelium and connective tissue cells. RESULTS: Ameloblastoma showed stronger bcl-2 expression than odontogenic keratocysts and radicular cysts. Bcl-2 expression in the whole thickness of epithelium and connective tissue of odontogenic keratocyst was significantly higher than radicular cyst. The expression of bax in the epithelium of radicular cyst was significantly higher than odontogenic keratocyst and ameloblastoma. The lining epithelium of odontogenic keratocyst showed stronger Ki-67 expression than ameloblastoma and radicular cyst. CONCLUSION: The proliferation potential of the epithelium and the overexpression of various anti-apoptotic proteins in odontogenic epithelial tumors are quite significant for their clinical behaviour. High expressions of bcl-2 and Ki-67 in odontogenic keratocysts accord with their aggressive clinical behaviour and a high recurrence rate.

The role of RANK/RANKL/OPG signalling pathways in osteoclastogenesis in odontogenic keratocysts, radicular cysts, and ameloblastomas.

The aim of this study was to evaluate the immunohistochemical expression of molecules involved in osteoclastogenesis, including the receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) in odontogenic keratocysts (OKCs), which has been named as a keratocystic odontogenic tumour by the WHO, and compare their expression with radicular cysts and ameloblastomas. RANK is a member of tumour necrosis factor receptor family and it is activated by RANK ligand. OPG binds to RANKL and inactivates it. The imbalance of these factors could cause the differential bone resorption activity in some diseases and tumours. The expression of these molecules was evaluated in ameloblastomas (n = 20), OKCs (n = 20), and radicular cysts (n = 20) by immunohistochemistry. Immunohistochemical reactivity for RANK, RANKL, and OPG was detected in neoplastic and nonneoplastic epithelium and connective tissue cells. RANK showed the greatest expression in OKCs followed by ameloblastomas, with the lowest expression seen in radicular cysts. Expression of RANKL was detected in all lesions and no significant differences were observed between groups. OPG was expressed very low in all groups. In the stroma, the number of RANK positive cells was higher in OKCs when compared with ameloblastomas and radicular cysts but radicular cyst had higher numbers of RANKL positive cells in the stroma than ameloblastomas. The molecular system of RANK/RANKL/OPG is variably expressed in OKCs, radicular cysts, and ameloblastomas and this system may be involved in the osteoclastogenic mechanisms in OKCs and ameloblastomas. Advanced studies could further clarify the role of RANK, RANKL, and OPG in mediating tumour associated bone osteolysis.