Therapeutic Potential of Silymarin in Mitigating Paclitaxel-Induced Hepatotoxicity and Nephrotoxicity: Insights into Oxidative Stress, Inflammation, and Apoptosis in Rats.

Background: Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits. Aims: To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways. Study Design: Experimental animal model. Methods: The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models. Results: SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (p < 0.05). Conclusion: Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes.

Molecular mechanisms of resveratrol and its silver nanoparticle conjugate in addressing sepsis-induced lung injury.

Sepsis is a life-threatening condition characterized by a systemic inflammatory response to infection. Despite extensive research on its pathophysiology, effective therapeutic approaches remain a challenge. This study investigated the potential of resveratrol (RV) and silver nanoparticle-enhanced resveratrol (AgNP-RV) as treatments for sepsis-induced lung injury using a rat model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The study focused on evaluating changes in oxidative status (TAS, TOS, and OSI) and the expression of inflammatory and apoptotic markers (IL-1ß, TNF-α, P2X7R, TLR4, Caspase-3, and Bcl-2) in lung tissue. Both RV and AgNP-RV demonstrated potential in mitigating oxidative stress, inflammation, and apoptosis, with AgNP-RV exhibiting greater efficacy than RV alone (p < 0.05). These findings were corroborated by histopathological analyses, which revealed reduced tissue damage in the RV- and AgNP-RV-treated groups. Our study highlights the therapeutic potential of RV and, particularly, AgNP-RV in combating sepsis-induced oxidative stress, inflammation, and apoptosis. It also underscores the promise of nanoparticle technology in enhancing therapeutic outcomes. However, further investigations are warranted to fully understand the mechanisms of action, especially concerning the role of the P2X7 receptor in the observed effects. Nonetheless, our research suggests that RV and AgNP-RV hold promise as novel strategies for sepsis management.

Anticarcinogenic Effects of Gold Nanoparticles and Metformin Against MCF-7 and A549 Cells.

Metformin is commonly prescribed to people with diabetes. Metformin has been shown in previous studies to be able to prevent the growth of cancer cells. This study aims to investigate the effects of metformin and gold nanoparticles in MCF7 breast cancer and A549 lung cell lines. The effects of metformin and gold nanoparticles on MCF7 breast cancer and A549 lung cells were determined on cells grown in 24 h cell culture. MCF-7 and A549 cells were incubated for 24 h with the treatment of escalating molar concentrations of ifosfamide. The MTT assay was used to determine the cytotoxicity of metformin toward MCF7 and A549 cell lines. The expression of Bax, BCL2, PI3K, Akt3, mTOR, Hsp60, Hsp70, and TNF-α was measured by RT-PCR. Metformin and gold nanoparticles inhibited the proliferation of MCF-7 and A549 cells in a dose and time-dependent manner with an IC50 value of 5 µM and 10 µg/mL. RT-PCR assays showed ifosfamide + metformin + gold nanoparticles significantly reduced the expression of BCL2, PI3K, Akt3, mTOR, Hsp60 and Hsp70 and increased the expression of TNF-α and Bax. The findings obtained in this study suggest that further studies should be conducted, and metformin and gold nanoparticles can be used in breast cancer and lung cancer treatments.

Citrate-coated silver nanoparticles loaded with agomelatine provide neuronal therapy in acute cerebral ischemia/reperfusion of rats by inhibiting the oxidative stress, endoplasmic reticulum stress, and P2X7 receptor-mediated inflammasome.

Cerebral ischemia and reperfusion are related to various situations like injuries after various traumas, oxidative stress, increased calcium ion, capillary hypoperfusion, microvascular hyperpermeability, leukocyte infiltration, and blood-brain barrier disruption. An antidepressant Agomelatine which is a melatonin receptor (MT1/MT2) agonist and serotonin receptor (5-HT2C) antagonist has been reported by studies to have antioxidant and anti-inflammatory effects. In our study, we aimed to detect the effects of citrate-coated silver nanoparticle-loaded agomelatine application on neurodegeneration, endoplasmic reticulum stress, autophagic and apoptotic cell death, inflammation, and P2X7R expression in the cerebral ischemia-reperfusion model to facilitate the passage of blood-brain barrier. Forty two Sprague-Dawley rats in total were divided into six equal groups (n:7) and applications were performed. Acute cerebral injury in the ischemia-reperfusion model was created 2 h after internal carotid artery ligation in rats and then at the 2nd hour of reperfusion citrate-coated silver nanoparticles loaded with Agomelatine were applied. Twenty four hours later, neurologic analysis on animals in experimental groups was performed, animals were decapitated and GSH, GPx, SOD, CAT, MDA, IL-1ß, and TNF-α parameters were examined after taking blood and the cerebral tissue samples. As a result, it was determined that ischemia-reperfusion caused endoplasmic reticulum stress in the cerebral tissues and thus caused cellular injury.

Effects of dietary thyme and rosemary essential oils on biochemical parameters, anti-oxidant metabolism, small intestinal morphology and myofiber structure of superficial pectoral and biceps femoris muscles in broilers.

This study was aimed at determining the effects of dietary supplementation with thyme essential oil (TEO) and rosemary essential oil (REO) on blood parameters, the anti-oxidant metabolism in the liver, breast and drumstick muscle tissues, the morphology of the small intestine, and the myofibril structure of the superficial pectoral and biceps femoris muscles. For this purpose, 400 three-day-old male Ross 308 chicks were used. Five groups, each comprising 80 broilers, were established. The control group was fed on a basal diet alone and groups thyme-1, thyme-2, rosemary-1 and rosemary-2 received basal diets supplemented with 0.15 g kg-1 of TEO, 0.30 g kg-1 of TEO, 0.10 g kg-1 of REO and 0.20 g kg-1 of REO, respectively. The serum total cholesterol and low-density lipoprotein levels were decreased significantly in group thyme-1. Dietary TEO and REO significantly increased glutathione levels in all tissues. Drumstick catalase activity was significantly increased in groups thyme-1, thyme-2 and rosemary-2. Superoxide dismutase activity was significantly increased in the breast muscle of all groups that received dietary TEO and REO. Histomorphometrical analyses demonstrated that dietary supplementation with TEO and REO increased both crypt depth and villus height in the small intestine. In result, the tested doses of dietary TEO and REO were ascertained to improve the intestinal morphology and to increase the anti-oxidant metabolism mainly in the breast muscle, the drumstick muscle and liver.

Blockade of P2X7 receptor-mediated purinergic signaling with A438079 protects against LPS-induced liver injury in rats.

The study aimed to investigate the hepatoprotective effects of purinergic receptor (P2X7R) antagonism by A438079 in liver damage. An experimental model of inflammation was performed by intraperitoneal (i.p.) lipopolysaccharide (LPS) administration in the rat. The groups were Control, A438079, dimethyl sulfoxide (DMSO), LPS, LPS + DMSO, and LPS + A438079. Following LPS (8 mg/kg) injection, A438079 (15 mg/kg) and DMSO (0.1 mL) were administrated (i.p) in the study groups. The blood and the liver tissues were removed for histological, biochemical, and western blot analyses. In the biochemical analysis, serum aspartate transaminase (AST) and alanine transaminase (ALT) concentrations, the tissue glutathione (GSH) level, and superoxide dismutase (SOD) activity dramatically decreased and malondialdehyde (MDA) level increased in the LPS and LPS + DMSO groups compared to the LPS + A438079 group. In the histological analysis, severe sinusoidal dilatation, necrotic hepatocytes, and inflammatory cell infiltration were observed in the LPS and LPS + DMSO groups while these effects were lessened in the LPS + A438079 group. The relative protein expression levels of P2X7R, Nf-kB-p65, IL-6, and Caspase-3 were significantly higher in the LPS and the LPS + DMSO groups than in the LPS + A438079 group. On the other hand, these protein expressions were considerably lower in the Control, A438079, and DMSO groups compared to the LPS + A438079 group. In addition, Bcl-2 protein expression was significantly lower in the LPS and the LPS + DMSO groups and higher in the LPS + A438079 group compared to the other groups. The protective effect of A438079 against LPS-induced hepatic inflammation may be related to P2X7R antagonism, inflammatory mediators, and apoptotic cell death.

Evaluation of the toxicological effects of favipiravir (T-705) on liver and kidney in rats: biochemical and histopathological approach.

Favipiravir is a selective RNA polymerase inhibitor and a broad-spectrum antiviral drug, an important agent used in viral infections, including Ebola, Lassa, and COVID-19. This study aims to evaluate the potential toxicological effects of favipiravir administration on rats' liver and kidney tissues. Favipiravir was applied for five and ten days in the present study. During this period, it was aimed to determine possible toxic effects on the liver and kidney. For this purpose, the impact of favipiravir on liver and kidney tissues were examined using histopathologic and biochemical methods. The present study showed that favipiravir administration led to an elevation in the liver and kidney serum enzymes and oxidative and histopathologic damages. Favipiravir administration caused apoptotic cell death (Caspase-3 and Bcl-2), inflammation (NF-κB and IL-6), and a decrease in renal reabsorption (AQP2) levels. In the evaluation of the findings obtained in this study, it was determined that the favipiravir or metabolites caused liver and kidney damages.

The increase of neuropathic symptoms in diabetic patients is related with osteopenia.

PURPOSE: To investigate the relationship between the intensity of neuropathic pain and the severity of osteopenia in type 2 diabetic patients with painful diabetic peripheral neuropathy (painful DPN). METHODS: In 220 patients with type 2 diabetes included in the screening, the presence of neuropathic pain was evaluated using the Douleur Neuropathique 4 Questions (DN4) scoring system. One hundred forty-five patients with painful DPN were identified and included in the study. Socio-demographic and laboratory evaluations were made and bone mineral density (BMD) of these patients was evaluated by the dual-energy x-ray absorptiometry (DEXA) method. RESULTS: There was a significant correlation between the neuropathic pain score and the total T scores of the lumbar spine and femur in patients with painful DPN. According to the regression analysis (standard coefficients), the DN4 score (0.498); the level of vitamin D (- 0.246) and the female sex (0.236) for the lumbar spine region; age (0.387); DN4 score (0.261); and vitamin D level (- 0.155) for the femur region were independently influencing factors on the development of osteoporosis. When osteoporosis (T score ≤ - 2.5) of the lumbar spine was analyzed by binary logistic regression, the risk of osteoporosis in women was 4.4 times higher, and the risk increased with increasing DN4 score. CONCLUSION: The increase of neuropathic symptoms in patients with DPN is an effective and important factor in the development of diabetic osteopenia.

Differentially regulated ADAMTS1, 8, 9, and 18 in pancreas adenocarcinoma.

INTRODUCTION: Despite recent diagnostic and therapeutic improvements, pancreas cancer remains one of the highly lethal cancers. The extracellular matrix (ECM) is a physiological barrier that limits the spread of cancer cells into surrounding tissues and distant organs. Disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) is a family of 19 proteases, which is involved in various biological processes such as ECM remodelling and anti-angiogenesis. AIM: To investigate the expression of ADAMTS1, 8, 9, and 18 proteinases in pancreas adenocarcinoma and its nodal metastasis. MATERIAL AND METHODS: The immunostaining status of ADAMTS1, 8, 9, and 18 were investigated in formalin-fixed paraffin-embedded samples of 25 patients who underwent pancreaticoduodenectomy for an adenocarcinoma located at the head of the pancreas. RESULTS: In semi-quantitive grading pathologically, ADAMTS1, 8, 9, and 18 were found to be highly stained in all cancerous pancreas samples compared with normal pancreas. In addition, the immune positivity of ADAMTS1, 9, and 18 was found to be higher in metastatic lymph nodes than in non-metastatic lymph tissue. Tumour size was correlated with ADAMTS9 and 18 expressions in cancerous pancreas. CONCLUSIONS: According to the data obtained from the study, we suggest that these four ADAMTSs may have significant roles in the tumorigenesis and nodal spread of pancreas adenocarcinoma.

Effects of immunosuppressive drugs on oral mucosa in patients with Behçet's disease: cytomorphological and cytopathological assessment.

BACKGROUND/AIM: The aim of this study was to investigate cytomorphological and cytopathological changes in oral exfoliated smears collected from immunosuppressed patients with Behçet's disease (BD) using stereological methods. MATERIALS AND METHODS: For cytomorphometric analysis, mucosal cell smears were obtained from the buccal mucosa and the floor of the mouths of BD patients treated with immunosuppressive drugs and from healthy volunteers. All mucosal smears from the patients and the healthy volunteers were stained using the Papanicolaou method and examined cytopathologically under light microscopy and cytomorphologically via the stereological nucleator method. RESULTS: The cytomorphological analysis revealed 3 types of mucosal cells, with numbers of particularly pink cells lower in the aphthous areas of the patients with BD compared to the healthy controls (P < 0.05). The nuclear volumes (NVs) and cytoplasmic volume (CVs) were significantly higher in the BD patients (P < 0.05), but the NV/CV ratio was higher only in the drug-use patient groups (P > 0.05). There was lower apoptotic activity in the nondrug-use patients with BD and in the immunosuppressive-taking BD patients. CONCLUSION: The findings suggest that quantifiably morphological and morphometric changes in oral mucosa can be detected by stereological techniques. Changes in these parameters may indicate malignant transformation in the oral mucosa.

Influences of Fucoxanthin on Alveolar Bone Resorption in Induced Periodontitis in Rat Molars.

The aim of this study was to evaluate the effects of systemic fucoxanthin treatment on alveolar bone resorption in rats with periodontitis. Thirty rats were divided into control, experimental periodontitis (EP), and experimental periodontitis-fucoxanthin (EP-FUCO) groups. Periodontitis was induced by ligature for four weeks. After removal of the ligature, the rats in the EP-FUCO group were treated with a single dose of fucoxanthin (200 mg/kg bw) per day for 28 consecutive days. At the end of the study, all of the rats were euthanized and intracardiac blood and mandible tissue samples were obtained for biochemical, immunohistochemical, and histometric analyses. Fucoxanthin treatment resulted in a slight decrease in tumor necrosis factor-α, interleukin-1ß, and interleukin-6 levels and a significant decrease in oxidative stress index. It was observed that fucoxanthin caused a significant reduction in receptor activator of nuclear factor kappa-ß ligand (RANKL) levels and a statistically non-significant elevation in osteoprotegerin and bone-alkaline phosphatase levels. There were no significant differences in alveolar bone loss levels between the EP and EP-FUCO groups. This experimental study revealed that fucoxanthin provides a limited reduction in alveolar bone resorption in rats with periodontitis. One of the mechanisms underlying the mentioned limited effect might be related to the ability of fucoxanthin to inhibit oxidative stress-related RANKL-mediated osteoclastogenesis.

Effect of agomelatine on adult hippocampus apoptosis and neurogenesis using the stress model of rats.

Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further.

Effects of Melatonin on Oxidative Stress Index and Alveolar Bone Loss in Diabetic Rats With Periodontitis.

BACKGROUND: The aim of this study is to evaluate the effects of systemic melatonin treatment on serum oxidative stress index (OSI) and alveolar bone loss (ABL) in rats with diabetes mellitus (DM) and periodontitis. METHODS: Seventy Sprague Dawley rats were divided into control, experimentally induced periodontitis (EP), DM, EP-DM, EP and melatonin treatment (EP-MEL), DM and melatonin treatment (DMMEL), and EP-DM-MEL groups. DM was induced by alloxan, after which periodontitis was induced by ligature for 4 weeks. After removal of the ligature, the rats in the melatonin groups (EP-MEL, DM-MEL, and EP-DM-MEL) were treated with a single dose of melatonin (10 mg/body weight) every day for 14 consecutive days. At the end of the study, all of the rats were euthanized, and intracardiac blood samples and mandible tissues were obtained for biochemical and histologic analyses. Serum levels of total oxidant status/total antioxidant status and OSI were measured. In addition, neutrophil and osteoclast densities and myeloperoxidase activities were determined in gingival tissue homogenates, and ABL was evaluated with histometric measurements. RESULTS: Melatonin treatment significantly reduced fasting plasma glucose levels in the rats with DM. In addition, reduced OSI and ABL levels were detected in the EP-MEL and DM-MEL groups; the reductions in the EP-DM-MEL group were found to be more prominent. Melatonin also significantly decreased the increased myeloperoxidase activities and osteoclast and neutrophil densities in the EP, DM, and EP-DM groups. CONCLUSION: It is revealed in this experimental study that melatonin significantly inhibited hyperglycemia-induced oxidative stress and ABL through antiDM and antioxidant effects in rats with DM and periodontitis.

Ameliorative effect of selenium in cisplatin-induced testicular damage in rats.

In this study, we investigated the protective effect of selenium (Se) on cisplatin (Cis) induced testicular damage using histopathological, immunohistochemical and biochemical approaches. Twenty-one male Wistar rats were equally divided into three groups of seven rats each: control (C), Cis, and Cis+Se. Cis and Cis+Se group rats received Cis at a dose of 12mg/kg b.w./day, intraperitoneally for 3 consecutive days. Cis+Se group rats received selenium via oral gavage 3mg/kg/day (twice-a day as 1.5mg/kg) until 11th consecutive days starting at 5 days before cisplatin injection. C group received only 0.9% NaCl intraperitoneally and orally at same time and at equal volume. After the treatment, the histopathological, immunohistochemical and biochemical examinations were performed. In seminiferous tubules of Cis treated rats were observed the most consistent findings characterized with vacuolization, desquamation, disorganization, and also was a considerable reduction in elongated spermatids, however the Cis+Se group exhibited improved histopathologic changes. In the immunohistochemical examinations, caspase-3 immunopositive cells displayed higher in the Cis group according to C and Cis+Se groups. Bcl-2 and NF-κB staining revealed a moderate number in the C group and significantly fewer in the Cis group compared to the Cis+Se groups. Additionally, MDA levels were also significantly increased in the Cis group in comparison to Control group, but pretreatment with selenium prevented elevation of MDA levels significantly in Cis+Se group rats. This study indicates that Cis-treatment induced testicular apoptosis and lipid peroxidation, and combined treatment with selenium prevented severity of the toxicity in rats.

Therapeutic Effects of Melatonin On Liver And Kidney Damages In Intensive Exercise Model of Rats.

Extensive exercise induces inflammatory reactions together with high production of free radicals and subsequent liver and kidney tissues damage. This study was designed to investigate for effects of melatonin on liver and kidney tissues in the extensive exercise exposed rats and non-exercised rats. In this research, 24-male Sprague-Dawley rats were divided into four groups. For exercise rat model, the rats were exposed to slow pace running with the velocity of 10 m/min for 5 minutes for five days just before the study. And for last ten days after adaptation period, the exercise was improved as 15 min with the speed of 20 m/min and intra-peritoneal melatonin injection has been performed to the melatonin treated groups with the dose of 10 mg/kg. Biochemical results revealed a decrease in the parameters of kidney and liver enzymes in exercise-group and an increase in the parameters of serum, liver and kidney enzymes in the group that melatonin-exercise-group. As for histological analysis, while it is observed that there are cellular degenerations in the liver and kidney tissues with exercise application, a decrease has been observed in these degenerations in the group that melatonin was applied. At the end of the research, it has been determined that exercise application causes some damages on liver and kidney, and these damages were ameliorated with melatonin treatment.

Effect of systemic clarithromycin and prednisolone on histamine-induced otitis media in guinea pigs.

CONCLUSION: The results of the study showed that clarithromycin has anti-inflammatory and antioxidant effects and, when it is combined with prednisolone, those effects gain strength. OBJECTIVES: The present study aims to investigate the effects that the antioxidant and anti-inflammatory activities of clarithromycin and/or prednisolone have on experimental otitis media in effusion-induced guinea-pigs. METHOD AND RESULTS: In this study, 35-male guinea pigs were randomly divided into five-groups. For the experimental otitis media, intra-tympanic histamine (0.1 ml) was injected into the guinea pigs in all of the groups except the control group. Then, 24-h after the intra-tympanic injections, clarithromycin (15 mg/kg/day) and/or prednisolone (1 mg/kg/day) were applied intraperitoneally to the guinea-pigs for 7-days. The biochemical analysis showed an increase in antioxidant capacity and a decrease in oxidant status and malondialdehyde (MDA) levels in the clarithromycin group and the prednisolone group and especially in the clarithromycin+prednisolone group, as compared to the experimental group (p < 0.05). In the cytokine analysis, lower levels of interleukin (IL)-6 and IL-17A and higher IL-10 were found in the clarithromycin, prednisolone, and clarithromycin+prednisolone groups than in the experimental group (p < 0.05). Furthermore, the histologic analyses showed histopathologic changes in the middle ear mucosa of the experimental group, but comparatively fewer-histopathologic changes were observed in the clarithromycin, prednisolone, and clarithromycin+prednisolone groups.

Therapeutic Effects of Melatonin on Alveolar Bone Resorption After Experimental Periodontitis in Rats: A Biochemical and Immunohistochemical Study.

BACKGROUND: The present study aims to investigate the effects of systemic melatonin administration on alveolar bone resorption in experimental periodontitis in rats. METHODS: Twenty-four male Sprague-Dawley rats were divided into three groups (control, experimental periodontitis [Ped], and experimental periodontitis treated with melatonin [Mel-Ped]). For periodontitis induction, first molars were ligatured submarginally for 4 weeks. After ligature removal, rats in the Mel-Ped group were treated with a daily single dose of 10 mg/kg body weight melatonin for 15 consecutive days. At the end of the study, intracardiac blood samples and mandible tissues were obtained for histologic, biochemical, and radiographic analysis. Serum markers related to bone turnover, calcium, phosphorus, bone alkaline phosphatase (b-ALP), and terminal C telopeptide of collagen Type I (CTX) were analyzed. Myeloperoxidase levels were determined in gingival tissue homogenates, and receptor activator of nuclear factor-kappa B ligand (RANKL) activation was analyzed in the mandible samples stereologically. Alveolar bone loss was also evaluated radiographically in the mandible samples of each group. RESULTS: Melatonin treatment decreased serum CTX levels and increased b-ALP levels. Serum calcium and phosphorus levels were not statistically different among groups (P >0.05). Alveolar bone resorption and myeloperoxidase activity were statistically higher in the Ped group compared to the Mel-Ped group (P <0.05). Immunohistochemical staining of RANKL and osteoclast activity were significantly lower in the Mel-Ped group compared to the Ped group (P <0.05). CONCLUSION: This study reveals that melatonin treatment significantly inhibits regional alveolar bone resorption and contributes to periodontal healing in an experimental periodontitis rat model.

Ultra-structural changes and apoptotic activity in cerebellum of post-menopausal-diabetic rats: a histochemical and ultra-structural study.

Diabetes mellitus (DM) is one of the most common and chronic diseases, especially in post-menopausal periods. Neuro-degeneration occurs more frequently in post-menopausal diabetics. Therefore, we investigated ovariectomized rats cerebellar cortex response to the estradiol deficiency and hyperglycemia. For the ovariectomy, the rats were bilaterally ovariectomized, and then DM induced by a single dose of Alloxan monohydrate injection in ovariectomy or/and diabetic groups. During light and electron microscopic examination, degenerated Purkinje cells membrane, swollen organelles, degenerated mitochondria, edema formation and vacuolization were seen in the ovariectomy and ovariectomy-diabetic groups sections. In addition, increased apoptotic activity was observed in the ovariectomy and ovariectomy-diabetic groups compared to the control group. We demonstrated that estradiol and insulin deficiency can affect the cerebellar cortex, which support the hypothesis that the execution of neuronal damages in post-menopausal diabetics. Also, diabetes and menopause are major risks factors for many disorders including nervous system and the number of post-menopausal-diabetics are increasing world-wide.

Immune modulatory and antioxidant effects of melatonin in experimental periodontitis in rats.

Melatonin is an important antioxidant, and through its anti-inflammatory effects it can control immune responses, oxidative stress, and defense cell infiltration. Periodontitis is a disease of the oral cavity and the generation of free radicals is an important consideration in this disease. Therefore, we examined the immune-modulatory and antioxidant roles of melatonin in the treatment of periodontitis. In all, 30 male Wistar rats were randomly divided into three groups: the control group, the periodontitis-induced (PED) group, and the periodontitis+melatonin treatment (MEL+PED) group. The control group received no treatment, whereas periodontitis was induced in both the PED and the MEL+PED groups, with the MEL+PED group being treated with systemic melatonin. For the periodontitis-induced groups, the rats' mandibular first molar teeth were ligatured (3-0 cotton) in a submarginal position for 4 weeks, and then the ligature was removed. After removal of the ligature, melatonin was administered only to the MEL+PED group (an ip dose of 10mg/kg body wt for 15 days at 11:00 PM each day). In the histological examination, the MEL+PED group, which received the melatonin, showed reduced inflammatory cytokines (IL-1ß, from 97.47 to 84.24pg/ml; TNF-α, from 0.22530 to 0.22519pg/ml), regulated oxidative stress parameters (MDA, from 41,458 to 30,708nmol/g; GSH, from 18,166 to 25,858nmol/mg), and less periodontal tissue destruction (CEJ-PL, lingual, from 244.54 to 140.57µm; buccal, from 235.6 to 158.93µm; and CEJ-BC, lingual, from 383.65 to 287.76µm; buccal, from 391.92 to 296.12µm). From these findings we conclude that, even when periodontitis was induced, melatonin reduced the oxidative damage in the rats' periodontal tissue by inhibiting the inflammatory effects and by restoring the antioxidants.