The Preventive Effect of Preoperative and Postoperative Selenium on the Medication-Related Osteonecrosis of the Jaw: An Animal Study in Rats.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a condition that can occur primarily in patients undergoing or have previously undergone therapy with bisphosphonates, particularly in the presence of risk factors, such as tooth extraction (TE). PURPOSE: This study aimed to evaluate the effect of selenium (SEL) administration on the prevention of osteonecrosis of the jaw in an MRONJ animal model. STUDY DESIGN, SETTING, AND SAMPLE: This study was a longitudinal in vivo animal study using a TE model in a sample of 48 Wistar rats. PREDICTOR VARIABLE: The predictor variables were SEL exposure, timing of SEL exposure, and zoledronic acid (ZOL) exposure. The animals were randomly assigned to 4 treatment groups (n = 12 per group): 1) saline (negative control), 2) ZOL (positive control), 3) SELpreop + ZOL, and 4) ZOL + SELpostop. The animals were administered saline (negative control) or ZOL (0.06 mg/kg, intraperitoneally) once a week for 5 weeks. All rats underwent TE at the end of the fifth week. SEL (0.3 mg/kg, intraperitoneally) was administered once daily for 15 days to the SELpreop + ZOL group before TE and to the ZOL + SELpostop group after TE. All animals were sacrificed at the end of the ninth week. MAIN OUTCOME VARIABLES: The primary outcome variables were new bone area, necrotic bone area, fibrosis, new connective tissue formation, and inflammatory cell infiltration in the histopathological analysis, as well as angiogenesis and percentage of osteoblasts in the immunohistochemical analysis. COVARIATES: There was none. ANALYSES: Statistical analysis was conducted using the Kruskal-Wallis test, followed by post hoc Bonferroni-corrected Mann-Whitney U tests, with a significance level of P ≤ .05. RESULTS: The new bone area was higher in the ZOL + SELpostop group (3.00 score) than in the saline group (0.58 ± 1.08 score, P < .001) and the ZOL group (0.82 ± 1.40 score, P = .001), while the necrotic bone area was lower in the ZOL + SELpostop group (0.08 ± 0.29 score) than in the ZOL group (2.82 ± 0.40 score, P < .001) and the SELpreop + ZOL group (1.67 ± 0.89 score, P = .007). The percentage of osteoblasts was higher in the ZOL + SELpostop group (18.73%) than in the saline group (8.63%, P < .001) and the ZOL group (0.07%, P < .001), and it was also higher in the SELpreop + ZOL group (18.49%) than in the ZOL group (0.07%, P < .001). CONCLUSION AND RELEVANCE: In conclusion SEL prevents MRONJ, with postoperative SEL demonstrating greater prevention effects. Given these findings, we hypothesize that SEL exposure may decrease the risk of MRONJ.

The Impact of the High-Fructose Corn Syrup on Cardiac Damage via SIRT1/PGC1-α Pathway: Potential Ameliorative Effect of Selenium.

High-fructose corn syrup (HFCS) has been a subject of intense debate due to its association with cardiovascular risks. This study investigates the potential protective effects of selenium (Se) supplementation against cardiac damage induced by HFCS. Thirty-two male Wistar albino rats were divided into four equal groups: control, CS (20%-HFCS), CS with Se (20%-HFCS, 0.3 mg/kg-Se), and Se (0.3 mg/kg-Se) only. After a 6-week period, heart and aorta tissues were collected for histopathological, immunohistochemical, biochemical, and genetic analyses. HFCS consumption led to severe cardiac pathologies, increased oxidative stress, and altered gene expressions associated with inflammation, apoptosis, and antioxidant defenses. In the CS group, pronounced oxidative stress within the cardiac tissue was concomitant with elevated Bcl-2-associated X protein (Bax) expression and diminished expressions of B-cell-lymphoma-2 (Bcl-2), nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), and silenced information regulator 1 (SIRT1). Se supplementation mitigated these effects, showing protective properties. Immunohistochemical analysis supported these findings, demonstrating decreased expressions of caspase-3, tumor necrosis factor-alpha (TNF-α), IL-1ß, and vascular endothelial growth factor (VEGF) in the CS + Se group compared to the CS group. The study suggests that Se supplementation exerts anti-inflammatory, antioxidant, and antiapoptotic effects, potentially attenuating HFCS-induced cardiovascular toxicity. These findings highlight the importance of dietary considerations and selenium supplementation in mitigating cardiovascular risks associated with HFCS consumption.

Histochemical, Immunohistochemical, and Biochemical Investigation of the Effect of Resveratrol on Testicular Damage Caused by Methotrexate (MTX).

Cancer is one of the world's major causes of death. The aim of this study is to examine the acute effects of resveratrol on testicular toxicity, oxidative stress, and apoptosis caused by MTX, which is widely used in the treatment of many diseases, especially cancer, histochemically, immunohistochemically, and biochemical methods using different parameters. A total of 32 Wistar albino male rats were randomly divided into 4 groups: control, resveratrol (RES), MTX, and MTX + RES, with 8 animals in each group. At the end of the experiment, tissue and blood samples were taken, and histochemical, immunohistochemical, and biochemical parameters were examined. In this study, where parameters were compared for the first time, total thiol (TT) and native thiol (NT) are the highest in the RES group, disulfide (DS), and ischemia-modified albumin (IMA) are the highest in the MTX group. Total oxidant status (TOS) and oxidative stress index (OSI) are the highest in the MTX group, and total antioxidant status (TAS) is the highest in the RES group. Separation and deterioration in the tunica albuginea, congestion and edema in the interstitial region, vacuolization in the seminiferous epithelium, and spermatogenic serial cells spilling into the lumen without completing their maturation were observed. When examined in terms of histochemical, immunohistochemical, and biochemical examinations, our study revealed that resveratrol has positive effects on methotrexate-induced acute testicular damage, oxidative stress, and apoptosis.

Immunochemical identification of the mammalian peptide hormone obestatin from tea plant (Camellia sinensis).

This study determines obestatin-like substances from the young shoots of the tea plant [Camellia sinensis (L.) O. Kuntze (Theaceae)]. Proteins were extracted from the vegetative tea leaves using the QB (Quick Buffer) buffer as an extraction buffer. Obestatin-like substances in tea extract were investigated using an indirect home-made enzyme-linked immunosorbent assay (ELISA). Human obestatin-like immunoreactive substances from tea extract were isolated and characterized by tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (tricine-SDS-PAGE) and immunoblotting techniques. Immunochemical results showed that there are strong human obestatin-like immunoreactive substances (0.048±0.0064ng/mg protein) in vegetative tea leaves. This finding was completely unexpected since this hormone was considered to be present solely in animals. Furthermore, a single obestatin-like immunoreactive protein band of 13kDa was identified by tricine-SDS-PAGE and Western blotting of extract of vegetative tea leaf proteins. Present investigation is the first report of presence of obestatin-like immunoreactive substances in plants. It is concluded that obestatin-like bioactive peptides derived from plants can affect gastrointestinal tract structures as endogenous obestatin does and hence play a role in appetite regulation and body weight gain.

Investigation of inflammation, oxidative stress, and DNA damage in COVID-19 patients.

COVID-19 disease, which spreads worldwide, is a disease characterized by widespread inflammation and affects many organs, especially the lungs. The resulting inflammation can lead to reactive oxygen radicals, leading to oxidative DNA damage. The pneumonia severity of 95 hospitalized patients with positive RT-PCR test was determined and divided into three groups: mild, moderate, and severe/critical. Inflammation markers (neutrophil-lymphocyte ratio, serum reactive protein, procalcitonin, etc.) were determined, and IL-10 and IFN-γ measurements were analyzed using the enzyme-linked immunosorbent assay method. In evaluating oxidative damage, total thiol, native thiol, disulfide, and ischemia-modified albumin (IMA) levels were determined by measuring spectrophotometrically. The comet assay method's percentage of tail DNA obtained was used to determine oxidative DNA damage. As a result, when the mild and severe/critical groups were compared, we found that total thiol, native thiol, and disulfide levels decreased significantly in the severe/critical group due to the increase in inflammation markers and cytokine levels (p < 0.05). We could not detect any significance in IMA levels between the groups (p > 0.05). At the same time, we determined an increase in the tail DNA percent level, that is, DNA damage, due to the increased oxidative effect. As a result, we determined that inflammation and oxidative stress increased in patients with severe pneumonia, and there was DNA damage in these patients.

Selenium exerts protective effects on inflammatory cardiovascular damage: molecular aspects via SIRT1/p53 and Cyt-c/Cas-3 pathways.

BACKGROUND: Systemic inflammatory response could affect many systems. Cardiac dysfunction develops due to cardiovascular system damage and could be mortal. Selenium is a trace element that can be used as a dietary supplement and has antioxidant, anti-inflammatory, and anti-apoptotic properties. This study aims to evaluate the protective effects of selenium on cardiovascular damage via silenced information regulator 1 (SIRT1)/p53 and cytochrome C (Cyt-c)/ caspase-3 (Cas-3) pathways. METHODS AND RESULTS: Thirty-two rats were randomly divided into 4 groups as control, LPS (0.1 mg/kg, intraperitoneally(i.p.), 2-7 days) and LPS + Selenium (LPS-0.1 mg/kg, i.p., 2-7 days, selenium - 100 µg/kg, i.p., 1-7 days) and selenium (100 µg/kg, i.p., 1-7 days) group. On the 8th day of the experiment, rats were sacrificed. Blood samples and half of the left ventricles were collected for biochemical and genetic analysis. The remaining left ventricles and aorta were taken for histological and immunohistochemical analysis. In the LPS group myocardial hemorrhages, hyperemia, and endothelial cell loss were observed. Also, Cas-3 and vascular endothelial growth factor (VEGF) expressions; creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), ischemia modified albumin (IMA), total oxidant status (TOS), oxidative stress index (OSI) levels; p53, Cyt-c, Cas-3 mRNA expressions increased while total antioxidant status (TAS) levels, glutathione peroxidase (GPx) activity, SIRT1 mRNA expression decreased. Selenium treatment reversed all these changes. CONCLUSION: Selenium showed protective effects on cardiovascular injury via regulating SIRT1/p53 and Cyt-c/Cas-3 pathways. This study enlightened the possible usage of selenium on cardiotoxicity.

"Theranekron: A Novel Anti-inflammatory Candidate for Acetic Acid-Induced Colonic Inflammation in Rats".

BACKGROUND: Inflammatory bowel disease (IBD) is characterized with chronic inflammation of gastrointestinal track. In the pathogenesis of IBD, inflammation is the main mechanism. Induction of inflammation triggers the oxidative stress that subsequently leading to apoptosis. Considering the all pathological mechanisms, many therapeutic agents have been used for IBD but because of serious side effects there is still a need for new therapeutic drugs. In this study, we aim to evaluate the possible protective effects of Theranekron (TH) on acetic acid (AA)- induced colonic damage and to describe the probable effect mechanisms of TH. MATERIALS AND RESULTS: Fourty female adult Wistar albino rats were divided into 5 groups. Following 24 h fasting, colitis was induced by rectal instillation of AA. In TH group, a single dose of subcutaneous 0.2 ml TH was used. In treatment groups, 0.2 ml TH single dose or 100 mg/kg sulfasalazine (SS) for 7 days were used after colitis induction. Normal salin was used for all applications in control group. Histopathologically hemorrhage, edema and inflammatory reactions were seen in AA group. TH and SS decreased the severity of lesions. Nuclear factor kappa B, Serum amyloid A, C-reactive protein, Growth-related oncogene, and Osteopontin expressions were markedly increased in AA group and TH markedly reduced these expressions. In Western analysis, decreased NF-kB and caspase-3 levels were observed with TH. Oxidative markers did not changed significantly. CONCLUSIONS: TH has a prominent anti-inflammatory effect on AA-induced colonic inflammation via NF-kB signaling whereas antiapoptic effects seem to be independent from this pathway.

Irbesartan decreased mitochondrial stress related apoptosis in cisplatin induced acute kidney injury via regulating BCL-2/BAX signaling.

BACKGROUND: Cisplatin (CPN) is used in the treatment of various cancers. However, the especially nephrotoxic effect is limiting its use. We aimed to evaluate the renoprotective effects of Irbesartan (IBN) on CPN-induced acute kidney injury via mitochondrial stress related apoptosis. METHODS AND RESULTS: 32 rats were divided into 4 groups as control, CPN, CPN + IBN and IBN. Water or IBN 50 mg/kg (orally) was administered for 7 days and a single dose of CPN (5 mg/kg) intraperitoneally was given CPN and CPN + IBN groups on fourth day of experiment. At the end of the experiment, serum BUN and creatinine (Cre) levels, which are the indicators of kidney function are measured. Bcl-2-associated X protein (Bax) and B-cell-lymphoma-2 (Bcl-2) mRNA levels were analyzed by using qRT-PCR from kidneys as a mitochondrial stress indicator. Also, active caspase-3(cas-3) protein and tumor necrosis factor alpha (TNF-α) expressions were examined by immunostaining of the kidney tissues. For evaluation of oxidative stress, malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels of renal tissues were measured and oxidative stress index (OSI) were calculated. CPN increased serum BUN and creatinine levels. Also, MDA, TOS and OSI levels were significantly elevated and TAS levels decreased in the CPN group. Moreover, CPN elevated the levels of Bax, active cas-3 protein and TNF-α expressions and suppressed Bcl-2 levels. IBN treatment reversed all these changes. CONCLUSIONS: IBN significantly regressed kidney damage by its anti-inflammatory and antioxidant activity via inhibiting mitochondrial stress. IBN could be used as a renoprotective agent in CPN-induced kidney injury.

The Possible Protective Effect of Boric Acid in an Alkaline-Induced Corneal Neovascularization Rat Model.

It is known that boric acid (BA) exerts it antioxidant and anti-inflammatory effects by activating the activating transcription factor 4 (ATF4) and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. This pathway has been reported to control antioxidant status in the eye. The aim of this study was to investigate the possible preventive effects of boric acid administration on oxidative damage and corneal neovascularization (CNV). Sixteen adult female Wistar albino rats were divided into two groups: (I) control (n = 8); the CNV model was applied to the right eye of the rats, and the left eyes were used as healthy controls. (II) CNV + BA (n = 8): After the CNV model was applied to the right eyes, a single subconjunctival dose (0.05 mL) of 0,018 g/mL BA was injected into the right and left eyes of the rats. Biochemical, histopathological, and immunohistochemical analyses were performed. Moderate VEGF positivity was observed in the vessels of the CNV group, a decrease in vessel proliferation, and weak VEGF positivity in the CNV + BA group. The TAS level in the CNV + BA group was significantly higher than that in the other groups. The TOS level was significantly higher in all groups than it is in the control group. The OSI value was increased in all groups when compared to the control group, but only the CNV and BA groups were statistically significant. BA not only reduced alkaline-induced corneal damage histologically but also showed a protective effect on oxidative stress biochemically.

Dexpanthenol may protect the brain against lipopolysaccharide induced neuroinflammation via anti-oxidant action and regulating CREB/BDNF signaling.

BACKGROUND: Neuroinflammation plays an important role in the pathogenesis of many psychiatric and neurodegenerative diseases. Dexpanthenol (Dex) is an alcoholic analogue of pantothenic acid with antioxidant, anti-inflammatory and anti-apoptotic properties. The purpose of this study was to determine the effect of dexpanthenol on lipopolysaccharide (LPS)-induced brain injury, specifically on the CREB/BDNF pathway. METHOD: Thirty-two rats were distributed into four groups: control, LPS, LPS + Dex and Dex groups. In this study, using real-time PCR, we evaluated changes in the gene expression of BDNF and CREB in the hippocampal brain tissue. Total antioxidant status (TAS), total oxidant status (TOS) were measured spectrophotometrically in the cortical tissue. Brain and cerebellum tissues were collected for histopathological examination and immunohistochemical assessment of tumor necrosis factor alpha (TNF-α) and caspase-3 (Cas-3). RESULT AND DISCUSSION: In the LPS + Dex group, TAS levels were significantly higher while TOS and OSI levels were significantly lower than the LPS group. In the LPS + Dex and Dex group, BDNF relative mRNA expressions were significantly higher than the LPS group. The levels of CREB relative mRNA expression in LPS and LPS + Dex group were significantly lower than the control group. An increased expression of Cas-3 and TNF-α in the LPS group and a decreased expression in the LPS + Dex group were observed in the immunohistochemical examination. CONCLUSION: According to these results, it may be considered that CREB-mediated BDNF synthesis may play a role in the etiopathogenesis of neuroinflammation. By regulating these changes with dexpanthenol treatment, a positive contribution may be made to neuroinflammation treatment.

A study on Wistar Albino rats: investigating protective role of ramelteon on liver damage caused by methotrexate.

Methotrexate is an important immunosuppressive and antineoplastic drug and is widely used for treatment. However, hepatotoxicity is one of the major adverse effects of methotrexate. In this study, it was aimed to investigate whether ramelteon has a possible protective effect on hepatotoxicity induced by methotrexate. Thirty-two Wistar albino rats were equally divided into four groups: control, methotrexate, methotrexate + ramelteon, and ramelteon. Following a single dose of 20 mg/kg, methotrexate (i.p.), either saline or ramelteon 10 mg/kg (orally) was administered for 7 days. After treatment, animals were sacrificed, and histopathological analyses were evaluated with Hematoxylin-eosin (H-E), immunohistological analyses were evaluated with Interleukin-1 Beta (IL-1ß) and Caspase 3 (CAS-3), biochemical analyzes were evaluated with Total Oxidant Status (TOS), Total antioxidants status (TAS), Oxidative Stress Index (OSI), aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities, at last genetical analyses were evaluated with Sirtuin-1 (SIRT-1) - P53 gene expressions. In the control and ramelteon groups, normal histological structures were observed, while histopathological findings were observed in the methotrexate group. Increasing levels of IL-1ß staining, CAS-3 staining, p53 gene expression, TOS, OSI, AST and ALT were observed in methotrexate group while were observed decreasing levels of TAS and SIRT-1 gene expression (p < 0.05). However, ramelteon reduced the increased findings in methotrexate-induced hepatotoxicity (p < 0.05). The results of the present study showed that ramelteon protects against methotrexate induced hepatotoxicity in rats via SIRT-1 signaling by histological, immunohistological, biochemical and genetical analyses.

Nebivolol alleviates liver damage caused by methotrexate via AKT1/Hif1α/eNOS signaling.

Despite the wide clinical indications, methotrexate (MTX) use is limited because of serious side effects including liver toxicity. MTX was shown to cause tissue damage by mainly oxidative stress and also inflammation and apoptosis. Thus, Nebivolol (NEB) which has antioxidant and antiapoptotic properties were thought to be effective against MTX-induced injury. This study aimed to evaluate the effects of NEB on MTX-induced liver toxicity via AKT/Hypoxia-Inducible Factor 1 Alpha (HIF1α)/Endothelial Nitric Oxide Synthase (eNOS) signaling pathways. Rats were divided into three groups as control, MTX, and NEB. A single dose of MTX (20 mg/kg intraperitoneally) was given to the rats on the first day of the experiment and NEB (10 mg/kg, daily by oral gavage) was given to the treatment group for a week. At the end of the experiment, bloods were taken for aspartate transaminase (AST), alanine aminotransferase (ALT), and total bilirubin (T-BIL) analyses. Liver tissues were harvested for biochemical (total oxidant status (TOS) and total antioxidant status (TAS), genetic (PCR analyses for AKT1, eNOS, and HIF1a), and histological (Hemotoxylin-Eosin, Masson Trichome, Periodic Acid Schiff-Asien Blue, reticulin for histological, and CD3 for immunohistochemical staining) analyses. MTX increased the levels of TOS values, AST, ALT, T-BIL levels and decreased the expressions of AKT/HIF1α/eNOS. NEB treatment reversed all these changes markedly via decreasing inflammation by nitric oxid (NO) production. In conclusion, NEB treatment significantly preserves the liver by decreasing oxidant levels and inflammatory parameters through HIF1α/eNOS signaling. Due to the antioxidant properties of NEB, it can be used in other liver injury models sharing the same pathway.

Modulation of Salubrinal-Mediated Endoplasmic Reticulum Stress in an Experimental Subarachnoid Hemorrhage Model.

BACKGROUND: Perfusion abnormalities due to vasospasm remain a major cause of morbidity and mortality in subarachnoid hemorrhage (SAH). Despite a large number of clinical trials, therapeutic options with strong evidence for prevention and treatment of cerebral vasospasm are rare. In this study, we aimed to evaluate the neuroprotective effect of salubrinal (SLB) in endoplasmic reticulum stress-induced apoptosis, a catastrophic consequence of vasospasm. METHODS: Thirty-two Wistar albino rats were divided into 4 groups of 8 rats each: control group, SAH, SAH+SLB, and SAH+nimodipine (NMN). In the SAH+SLB group, intraperitoneal SLB (1 mg/kg dose) administered 30 minutes after establishment of SAH, and in the SAH+NMN group, intraperitoneal NMN (0.1 mg/kg dose) was also administered 30 minutes after SAH. RESULTS: Higher total antioxidant status level, lower oxidative stress index, and significantly higher vascular endothelial growth factor-A (VEGF-A) level were detected in the SAH+SLB and SAH+NMN groups compared with the SAH group. There was a significant increase in eukaryotic translation initiation factor-2 alpha (elF2α) level in the SAH+SLB group compared with the SAH group. Histopathological evaluation revealed decrease in the subarachnoid hemorrhagic area, as well as in cortical edema and apoptotic bodies in the SAH+SLB and SAH+NMN groups. There was a significant decrease in caspase-3 staining in the SAH+SLB group, and the levels were significantly less in the SAH+NMN group than the SAH and SAH+SLB groups. CONCLUSIONS: SLB, selective inhibitor of eIF2α dephosphorylation, and NMN, a calcium channel blocker, can ameliorate SAH-induced damage. Inhibition of eIF2α dephosphorylation and enhanced VEGF-A production with SLB may protect brain tissue from apoptosis.

Effect of methylenetetrahydrofolate reductase gene polymorphisms and oxidative stress in silent brain infarction.

Ischemic infarctions occur under the influence of genetic and environmental factors. In our study, the role of ischemia-modified albumin and thiol balance, which are new markers in determining oxidative damage together with MTHFR gene polymorphisms and homocysteine levels, in the development of SBI was investigated. White matter lesions in the magnetic resonance imaging (MRI) results of the patients were evaluated according to the Fazekas scale and divided into groups (Grade 0, 1, 2, and 3). Homocysteine, folate, B12, IMA, total thiol, and native thiol were measured by biochemical methods. The polymorphisms in MTHFR genes were investigated by the RT-PCR method. According to our results, a significant difference was found between the groups in age, homocysteine, folate, IMA, total thiol, and native thiol parameters (p < 0.05). When we compared the groups in terms of genotypes of the C677T gene, we found a significant difference in TT genotype between grades 0/3 and 1/3 (p < 0.05). We determined that homocysteine and IMA levels increased and folate levels decreased in CC/TT and CT/TT genotypes in the C677T gene (p < 0.05). Considering our results, the observation of homocysteine and IMA changes at the genotype level of the MTHFR C677T gene and between the groups, and the deterioration of thiol balance between the groups suggested that these markers can be used in the diagnosis of silent brain infarction.

Prenatal exposure to artificial food colorings alters NMDA receptor subunit concentrations in rat hippocampus.

Exposure to artificial food color additives (AFCAs) has been implicated in the etiology of certain childhood hyperactivity and learning disabilities. N-methyl-D-aspartate receptors and alpha-7 nicotinic acetylcholine receptor (α7 nAChR) are involved in learning and memory. We administered a mixture of AFCAs (erythrosine, ponceau 4R, allura red AC, sunset yellow FCF, tartrazine, amaranth, brilliant blue, azorubine, and indigotine) to female rats during gestation to investigate the effects of prenatal exposure to AFCAs on neurobehavior, spatial learning, and memory in their offspring. We also investigated whether AFCAs modulate NR2A, NR2B, and α7 nAChR protein levels in their offsprings' hippocampi. Although spatial learning and memory were not altered, the offspring of rats exposed to AFCAs exhibited decreased motivation and increased despair-related behavior. NR2A and NR2B protein levels were significantly reduced in female offspring in the experimental group (p < 0.05), whereas α7 nAChR level was not significantly altered. Our results suggest that prenatal exposure to AFCAs may lead to sex-dependent alterations in glutamatergic signaling which may continue into adolescence.

The impact of electromagnetic radiation (2.45 GHz, Wi-Fi) on the female reproductive system: The role of vitamin C.

The present study investigated the effects of applied continuous 2.45 GHz electromagnetic radiation (EMR), which might cause physiopathological or morphological changes in the ovarian, fallopian tubal, and uterine tissues of rats. We proposed that the addition of vitamin C (Vit C) may reduce these severe effects. Eighteen female Sprague Dawley rats were randomly divided into three groups with six animals in each: Sham, EMR (EMR, 1 h/day for 30 days), and EMR + Vit C (EMR, 1 h/day for 30 days 250 mg/kg/daily). Total oxidant status (TOS) and oxidative stress index (OSI) levels increased ( p = 0.011 and p = 0.002, respectively) in the EMR-only group in ovarian tissues. In all tissues, TOS and OSI levels significantly decreased in the Vit C-treated group in ovarian, fallopian tubal, and uterine tissues ( p < 0.05). Anti-müllerian hormone levels significantly increased in the EMR group ( p < 0.05) and decreased in the Vit C-treated groups. Estrogen (E2) levels were unchanged in the EMR group, as the differences were not statistically significant. Immunohistochemical examination of the ovaries revealed significant increases in Caspase-3 expressions in the epithelial cells of the EMR group ( p < 0.05). In the EMR group, hyperemia was observed in uterine tissues. Also, Caspase-3 and Caspase-8 were significantly increased in the EMR group ( p < 0.001). Caspase-3 was significantly diminished with Vit C application in the ovarian and uterine tissues ( p < 0.05). Caspase-8 was significantly diminished only in uterine tissues ( p < 0.05). These results indicate that prolonged EMR exposure induced physiopathological changes in the ovarian, fallopian tubal, and uterine tissues due to oxidative damage. Under the conditions of this study, Vit C may have protective effects on female reproductive system against oxidative damage.

The evaluation of salivary oxidative stress in patients with familial Mediterranean fever and chronic periodontitis.

BACKGROUND: Familial Mediterranean fever (FMF) is an inherent autoinflammatory disease and have a high prevalence in Mediterranean countries. The aim of this study was to evaluate salivary levels of oxidative stress parameters in patients with FMF and chronic periodontitis. METHODS: The study population consists of 81 patients with FMF and 85 systemically healthy controls. The test and control groups were classified as chronic periodontitis and periodontally healthy [FMF-periodontitis (n = 37); FMF-periodontally healthy (n = 44); systemically healthy-periodontitis (n = 37); systemically and periodontally healthy (n = 48]. Total salivary samples were collected. Clinical periodontal parameters including plaque index, gingival index (GI), probing depth (PD), the percentage of bleeding on probing (BOP%), and clinical attachment level (CAL), were measured. Salivary total antioxidant status (TAS), total oxidant status (TOS), 8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA), and oxidative stress index (OSI) were evaluated. RESULTS: The FMF-periodontitis group had significantly higher levels of 8-OHdG, MDA, and OSI than that of the FMF-periodontally healthy group. In the FMF-periodontitis group, PD, 8-OHdG, MDA, and OSI levels were significantly higher than in the systemically healthy-periodontitis group (P = 0.035, P = 0.000, P = 0.000, and P = 0.000, respectively). 8-OHdG values were significantly correlated with BOP% and GI, and TOS values were significantly correlated with PD and CAL in the FMF-periodontitis group. CONCLUSIONS: In the presence of FMF and chronic periodontitis, there were increased salivary levels of oxidative stress. Thus, oxidative stress could be an important inflammatory mechanism in the FMF and chronic periodontitis. Further studies need to clarify the oxidative mechanisms of FMF and chronic periodontitis.

Serum, salivary, and tissue levels of plasminogen in familial Mediterranean fever, amyloidosis, and chronic periodontitis.

BACKGROUND: There are no published studies regarding the role of the plasminogen (PLG) system in familial Mediterranean fever (FMF), FMF-associated secondary amyloidosis, or chronic periodontitis (CP), although recent limited data have focused on the association between FMF and chronic periodontitis. Therefore, the aim of this study was to evaluate the serum, salivary, and gingival tissue levels of PLG in patients with CP, FMF, and amyloidosis. METHODS: The study population included 122 patients with FMF (only FMF, and FMF and amyloidosis and 128 individuals who were systemically healthy controls. Blood and salivary samples were obtained from the cases and controls, and clinical periodontal parameters were recorded. Serum and salivary PLG levels were assessed. The gingival tissue samples of the case and control groups were analyzed histopathologically and immunohistochemically for amyloid deposition and PLG. RESULTS: The amyloidosis group had significantly more severe clinical periodontal parameters than those of the FMF and systemically healthy groups (P < 0.05). Salivary levels of PLG were significantly higher in the FMF and amyloidosis groups compared with those in the control group (P < 0.001). The FMF with periodontitis and amyloidosis with periodontitis groups had higher salivary PLG levels compared with those in the CP group. Serum and salivary PLG levels were significantly associated with the clinical periodontal parameters in the FMF group. The amyloidosis cases had hyperplasia, severe inflammation, and activation of the gingiva. CONCLUSION: The PLG system could play an important role in inflammatory diseases, such as chronic periodontitis, FMF, and FMF-associated secondary amyloidosis.

The impact of methotrexate on lung inflammatory and apoptotic pathway biomarkers-The role of gallic acid.

BACKGROUNDS: The aim of this study was to investigate the effects of methotrexate (MTX) on the lung via inflammatory and apoptotic pathway biomarkers and the role of gallic acid (GA). METHODS: In this study, twenty four male Wistar-Albino rats weighing 300-350g were divided into 3 groups as follows; Control group (0.1ml/oral saline, for 7 days+2nd day i.p.). MTX group (20mg/kg, single dose, on 2nd day). MTX+GA group (15mg/kg, orally, for 7 days). Comet analysis, oxidant-antioxidant status, IMA were conducted. Histopathological analyses were evaluated. RESULTS: Comet assay on the blood, TOS and OSI values in the lung were increased in the group II compared with the control group (p<0.05). GA significantly reduced the comet score and IMA levels in the blood, TOS and OSI values in the lung tissue in group III compared with group II (p<0.05). Immunohistochemically PGE2, TNF-α, CRP, serum SAA, Caspase 3 and Caspase 9 expressions significantly increased in group II compared with the control group (p<0.001) and GA treatment ameliorated these parameters significantly in group III compared with group II (p<0.001). CONCLUSIONS: MTX caused oxidative stress and DNA damage in the blood tissue and caused oxidative damage, inflammation and apoptosis in the lung tissue.