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© 2022, King Abdulaziz City for Science and Technology.The purpose of current research was to assess the apoptotic effects of biofabrication silver nanoparticles (AgNPs) mediated by the aqueous extract of Phlomis armeniaca on human breast cancer cells (MCF-7 and MDA-MB-231) in monolayer (2D) and spheroid (3D) cultures. The biosynthesized AgNPs were characterized by UV–Vis spectrophotometer (the peaks of resonances at 432 nm), scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDS). 1–20 µM/mL AgNPs were applied to MCF-7 and MDA-MB-231 cell lines to determine IC50 values at 24, 48 and 72nd h and were found to be 10 µM/mL for both cell lines. Immunohistochemical staining results of BrdU, TUNEL, caspase-3 and Endo G in both 2D and 3D cultures and gene expression levels of caspases (caspase-3, -8 and -9) and Endo G were evaluated. Moreover, the total oxidant/antioxidant status (TOS–TAS) due to AgNPs application in both cell culture mediums was evaluated. AgNPs treatment results in both cell lines in both 2D and 3D cultures showed a significant decrease in the BrdU labeling index, while large amounts of cells were labelled with TUNEL and Endo G. In 2D culture, Endo G expression increased in MCF-7 cells at 48 and 72nd hours, while it increased significantly in MDA-MB-231 cells at all hours. OSI results show that ROS production is increased in cell medium treated with AgNPs. In conclusion, AgNPs mediated by Phlomis armeniaca, synthesized by a green method, successfully induced damage to mitochondria, resulting in cell cycle arrest and consequent cell proliferation blockade and death in both MCF-7 and MDA-MB-231 cells.

Fluopyram is a widely used new generation broad spectrum fungicide and its toxic effects are mostly unknown. In this study, it was aimed to observe the effect of fluopyram administration at different doses on mouse kidney tissues. 0.5, 1 and 2 mg/kg Fluopyram were administered to mice, their kidneys were taken and evaluated histopathologically and immunohistochemically. Hematoxylin-eosin staining and also immunostaining with caspase-3, TNF-α, NF-Kb antibodies was performed. When the control group and fluopyram administered groups were compared, significant differences were found (p

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-1 beta) 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-1 beta 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.

The purpose of current research was to assess the apoptotic effects of biofabrication silver nanoparticles (AgNPs) mediated by the aqueous extract of

Objective: The study aimed to evaluate the protective effects of resveratrol (RES) against methotrexate (MTX)-induced ovarian damage in female rats and were divided into 7 groups: Material and Methods: Control; MTX (15mg/kg-1st day); MTX (1st and 3rd day); MTX (1st, 3rd and 5th day); MTX (1st day) + RES (20mg/kg); MTX (1st and 3rd day) + RES; MTX (1st, 3rd and 5th day) + RES. Since there was only one animal left in groups 4 and 6 and no animals in group 7, these groups were excluded from the evaluation. Ovarian damage was evaluated by performing hematoxylin-eosin (H-E) and TUNEL staining on ovarian tissues of rats. TAS and TOS activities in ovarian tissues were evaluated spectrophotometrically. In addition, DNA damage in blood was evaluated by comet assay. Results: As a result of biochemical analyzes, TOS levels increased in MTX groups, group 2 and 3, compared to the control group, while TOS level decreased significantly in group 5. On the other hand, TAS level increased significantly in group 5 compared to groups 2 and 3. H-E staining results showed that MTX-induced damage improved with RES (group 5) treatment. Maximum positive staining in TUNEL image; observed in equal amounts in groups 2 and 3, then in group 5. In addition, the comet score, which indicates DNA damage, increased significantly in groups 2 and 3, while it decreased significantly in group 5. Conclusion: In line with the results of this study, it was observed that resveratrol may provide protective effects against methotrexate-induced ovarian damage due to its antioxidant properties.

Reaktif oksijen türlerinin (ROS) güçlü bir temizleyicisi olan resveratrolün (RES), böbrek hastalıkları da dahil olmak üzere çeşitli metabolik bozukluklara karşı koruyucu etkisi olduğu bildirilmektedir. Bu çalışma, dişi sıçanlarda metotreksat (MTX) ile indüklenen renal toksisitede resveratrolün nefroprotektif etkilerini değerlendirmeyi amaçlamaktadır. Çalışma, her grupta altı adet rat olacak şekilde üç gruba ayrıldı: Kontrol, MTX: (15 mg/kg, tek doz, i.p), MTX + RES grubu: (15 mg/kg MTX, tek doz, i.p + 20 mg/ kg RES, günde tek doz, oral gavaj, 7 gün). Serum renal fonksiyon belirteçleri (ürik asit, BUN ve kreatinin), renal homojenatlarda toplam oksidan (TOS) ve antioksidan durumu (TAS) gibi biyokimyasal parametreler ölçülerek nefroprotektif etkinlik yorumlandı. Ayrıca RES'in böbrekler üzerindeki etkisi histopatolojik ve immünohistokimyasal analizlerle değerlendirildi. MTX ile indüklenen ratlarda RES tedavisi, serum BUN, kreatinin ve renal TOS düzeylerinde anlamlı azalmanın yanında renal TAS'ta anlamlı bir artışla nefro-koruyucu etkilerini gösterdi. Histolojik boyama bulgularında da biyokimyasal verilere paralel olarak, RES’in koruyucu etkisinin olduğu gözlendi. İmmünhistokimyasal olarak sistemik inflamatuar yanıtın göstergelerinden biri olan TNF-α'nın RES tedavisi ile azaldığı belirlendi. Araştırmanın bulguları, ratlara MTX enjeksiyonundan 1 saat önce RES uygulamasının böbrek hasarı üzerinde iyileştirici etkisi olduğunu göstermektedir.

We investigated the potential neuroprotective effects of thymoquinone (TQ) on amikacin (AK) induced oxidative damage in rat brain. We used 21 male rats divided randomly into three equal groups. The control group was injected intraperitoneally (i.p.) with 0.5 ml 0.9% aqueous NaCl and given 1 ml 0.9% aqueous NaCl orally. The AK group was administered 1.2 g/kg aqueous AK i.p. as a single dose on the day 3 of the study. The AK + TQ group was given a single 1.2 g/kg dose of AK i.p. on the day 3 of the study plus 40 mg/kg/day TQ by oral gavage daily. Treatment with TQ increased serum ferritin and decreased serum calcium levels significantly. TQ also decreased NADPH oxidase-2, NADPH oxidase-4, and caspase-3 levels. Decreased malondialdehyde (MDA) levels and increased superoxide dismutase (SOD) and catalase (CAT) activities were detected in the AK + TQ group compared to the AK group. TQ administration inhibited lipid peroxide formation and blocked oxidative reactions, which reduced the MDA level and increased SOD and CAT activities induced by AK. Oxidative damage caused by AK was ameliorated by TQ treatment owing to its antioxidative and anti-apoptotic effects. TQ may be a potential therapeutic agent for reducing the severity of AK induced oxidative damage to the brain.

Valproic acid (VA), widely used as an antiepileptic, causes structural and functional kidney disorders. Whether thymoquinone (TQ) has a beneficial effect on valproic acid (VA)-induced nephrotoxicity has been investigated. Twenty-one male Spraque Dawley rats were grouped into control, VA, and VA + TQ groups (n=7 for per group). VA (500 mg/kg/day) and TQ (50 mg/kg/day) were applied to the rats orally for 14 days. They were euthanized on the 15th day of the treatment. The cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) gene expression levels, biochemical parameters, total antioxidant/oxidant statuses (TAS/TOS), oxidative stress index (OSI), histological and immunohistochemical analysis were performed to evaluate kidney toxicity. In the VA + TQ group, COX-1 expression levels increased, while COX-2 expression levels decreased. While the creatinine (Cr) and blood urea nitrogen (BUN) levels, production of caspase-3 (CAS-3) and NADPH oxidase-4 (NOX-4) were increased in the VA-treated group, they were decreased in VA + TQ group. Treatment with TQ against VA administration decreased TOS and OSI levels while increasing TAS. TQ protects the kidney against the toxic effects of VA.

Background/Aim: Colon cancer is one of the most common cancers. Treatment success and survival rates are not high enough with current approaches. Therefore, there is a need to develop new agents and treatment methods. Boric acid is the most frequently observed form of boron. Some epidemiological data suggest that environmental exposure to boric acid reduces the incidence of prostate cancer in men, cervical and lung cancers in women. Experimental studies show, boric acid reduces cell proliferation and stimulates apoptosis in some prostate, melanoma, breast cancer cell lines. In this study, it was investigated whether boric acid could be a new candidate molecule that could be used in the treatment of colon cancer.Materials and methods: The effects of boric acid on human colon adenocarcinoma cell line SW-480 were investigated with BrdU, TUNEL, Caspase-3, and AIF immunohistochemical studies in both 2D and 3D culture systems. In addition, a qRT-PCR study was carried out to determine the expression changes in key genes that take part in apoptosis.Results: We observed that boric acid suppresses cell proliferation and induces apoptosis both in 2D and 3D culture conditions. In addition, as a result of qRt-PCR studies, it was revealed that the observed apoptotic process was related to the TNF signaling pathway.Conclusion: Boric acid can be considered as a potential anti-cancer agent candidate for colon cancer treatment. Data Availability: All data generated or analyzed during this study are included in this published article.

Background. This experimental study aimed to assess the effects of Vitamins C and E on orthodontictooth movement. Methods. Fifty-one male Wistar albino rats were divided into six groups: five appliance groups and onecontrol group. The appliance groups had an orthodontic appliance consisting of a closed-coil springligated between the maxillary incisor and maxillary first molar (50 g). Vitamin E and C (150 mg/kg)were injected intraperitoneally per day in the first and second groups, respectively. Vitamins E andC (20 μL) were locally injected into the periodontal gap of the moving teeth in the third and fourthgroups, respectively, once every three days. No vitamin was injected in the last (fifth) appliance group.The experimental period was 18 days. Histological and biochemical (alkaline phosphatase, osteocalcin,and NTx levels) evaluations of the samples were performed, and maxillary incisor‒molar distance wasmeasured before and after the experiment. Results. The amount of tooth movement was similar in the appliance groups. All the vitamin groupsshowed significantly increased osteoblastic activity, while those treated with systemic vitamins exhibitedsignificantly increased numbers of collagen fibers on the tension side compared to the appliance controlgroup (PConclusion. Vitamin C and E supplements positively affected bone formation on the tension side of theteeth during experimental orthodontic tooth movement.

This study sought to assess the protective effects of resveratrol and avocado oil in relation to paracetamol-induced hepatotoxicity in rats. The rats were divided into five groups, namely the control, paracetamol (600 mg/kg), resveratrol (RES; 10 mg/kg) + paracetamol, avocado oil (AVO; 200 mg/kg) + paracetamol, and RES + AVO + paracetamol groups. The hepatoprotective activity was evaluated by measuring biochemical parameters such as the total antioxidant status (TAS) and the total oxidant status (TOS) in each rat's liver homogenates. Any DNA damage was assessed by means of a comet assay. The results showed that the TOS levels were significantly increased in the paracetamol group when compared with the control group. The TOS levels were found to be significantly lower in the paracetamol groups, in comparison with the RES, AVO, and RES + AVO groups. Moreover, the TAS levels significantly increased in the RES and RES + AVO groups when compared with the paracetamol group. The histopathological examination revealed necrotic areas in the rats' livers. Pretreatment with both RES and RES + AVO was found to reverse the oxidative stress parameters, DNA damage, and necrosis induced by paracetamol. These results suggest that a combination of REV and AVO may protect against paracetamol-induced hepatotoxicity due to their antioxidant properties.

BackgroundWe investigated the apoptotic effects of curcumin in the colon carcinoma cell line SW480.Methods and resultsCells were treated with 40–200μM curcumin for 24, 48, and 72h, and the IC50values were determined for each time interval. BrdU, caspase-3, and TUNEL staining results and the gene expression ofFADD,CASP8, andCASP3were evaluated. Curcumin treatments significantly inhibited cell proliferation and significantly induced apoptosis for 24, 48, and 72h. The proportion of BrdU-stained cells in the control groups were 58%, 57% and 61% and 28%, 27%, and 30% in the curcumin treatment groups at 24, 48, and 72h, respectively. The proportion of apoptotic cells was 28%, 29%, and 28% in the control groups and 59%, 61%, and 60% in the curcumin treatment groups at 24, 48, and 72h, respectively. As expected, caspase-3 staining also revealed a higher number of apoptotic cells in curcumin treatment groups at 24, 48, and 72h compared to controls. The proportion of Caspase-3-stained cells in the control groups were 23%, 25%, and 24% and 59%, 60%, and 62% in the curcumin treatment groups at 24, 48, and 72h, respectively. To prove caspase-3 staining results,FADD,CASP8, andCASP3gene expressions were evaluated by real-time qPCR. Unlike the immunohistochemical results, no statistically significant upregulation was found at 24 and 48h, while relative gene expressions ofFADD,CASP8, andCASP3was significantly upregulated at 72h. The expression level increase was 0.88-, 1.19-, and 2.11-fold forFADD, 1.25-, 1.29-, and 1.59-fold forCASP8, and 1.33-, 1.46-, and 3.00-fold forCASP3at 24, 48, and 72h, respectively.ConclusionsThese results suggest that curcumin may be a potential protective or treatment agent against colon cancer; however, further studies on curcumin-rich diets and curcumin bioavailability are required.

Natural health products and functional foods arefrequently consumed for the prevention and treatmentof many diseases. Flaxseed is one of the functional foods with anticancer, antiviral, antibacterial and antifungalproperties. In addition to its beneficial effects,excessive consumption without considering the appropriatedosage can cause toxic effects. In this study,it was planned to investigate the effects of differentamounts of flaxseed consumption on rat liver.Materials and MethodsRats were randomly divided into four groups with 8rats in each groups; control group and experimentalgroups which given flaxseed for 7 days; 1.4, 2.8 and5.6 g/kg/day, respectively. At the end of the experiment,histological, immunohistochemical and biochemicalanalyzes were performed on tissue and bloodsamples.ResultsSerum AST, ALT and ALP values are significantly higherin 5.6 g/kg of flaxseed compared to control group(p values 0.003, 0.012 and 0.009, respectively). Albuminvalues were significantly lower in experimentalgroups compared to the control group (p, Doğal sağlık ürünleri ve fonksiyonel gıdalar, birçokhastalığın önlenmesi ve tedavisi için tüketilmektedir.Keten tohumu antikanser, antiviral, antibakteriyel veantifungal özelliklere sahip fonksiyonel gıdalardan biridir.Yararlı etkilerinin yanı sıra bilinçsiz ve aşırı tüketilmesitoksik etkilere neden olabilmektedir. Bu çalışmada,farklı miktarlarda keten tohumu tüketimininsıçan karaciğeri üzerindeki etkilerinin araştırılmasıplanlanmıştır.Gereç ve YöntemSıçanlar; her grupta 8 adet olarak; kontrol grubu ve7 gün süreyle sırasıyla; 1.4, 2.8 ve 5.6 g/kg/gün ketentohumu verilen deney grupları şeklinde dört grubaayrılmıştır. Deney sonunda doku ve kan örneklerindehistolojik, immünohistokimyasal ve biyokimyasal analizleryapılmıştır.BulgularSerum AST, ALT ve ALP değerleri 5,6 g/kg keten tohumuverilen grupta kontrol grubuna göre anlamlıolarak daha yüksek gözlendi (p değerleri 0.003,0.012 ve 0.009). Albümin değerleri deney gruplarındakontrol grubuna göre anlamlı olarak düşük gözlendi(p

Dietary consumption of commercially prepared (often through processing) corn syrup can activate reactive oxygen species and the inflammatory pathways observed in kidney damage in humans and experimental animals. This study was designed to assess the effects of antioxidant properties of acetylsalicylic (ASA) and ascorbic acid (AA) on corn syrup (CS) induced renal injury. Forty male Sprague–Dawley rats (14–16 weeks) were randomly classified into 5 groups, each containing 8 rats: control group (C), CS group, CS+ASA group (ASA-10 mg/kg/day/po), CS+AA group (AA-200 mg/kg/day/po) and CS+ASA+AA group (combination treatment with ASA and AA doses). At the end of the experiment, blood and tissue samples were collected for biochemical, histopathological and immunohistochemical examinations. Malondialdehyde (p

Methotrexate is an immunosuppressive and antineoplastic drug that may induce hepatotoxicity. Resveratrol is a compound that has a protective effect thanks to its antioxidant role. In present study was aimed to investigate posibble protective effects of resveratrol in methotrexate induced hepatotoxicity. Eighteen Wistar Albino rats were equally divided into three groups: Control, Methotrexate, Methotrexate + Resveratrol. After a single dose of methotrexate (15 mg/kg, i.p.), resveratrol (10 mg/kg, orally) was applied for 7 days. Fallowing 7 days, rats were sacrificed. Histopathological (H-E staining), immunohistochemical (Tumor Necrosis Factor Alpha, inducible Nitric Oxide Synthases, Nuclear Factor Kappa) and biochemical (Total Oxidant Status, Total antioxidants Status and Oxidative Stress Index) analyses were assayed in liver tissue samples. Additionally, Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase and Total Biluribin activities were assayed in serum samples for biochemical analyses. Normal liver tissues were observed in control groups. Histopatholocigal changes, high staining of Tumor Necrosis Factor Alpha, inducible Nitric Oxide Synthases, Nuclear Factor Kappa, increasing levels of tissue Total Oxidant Status, Oxidative Stress Index and decreasing levels of tissue Total antioxidants Status were observed in methotrexate groups. Moreover, Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase and Total Biluribin levels increased in methotrexate groups too (p

Background: Colon cancer is a major cause of morbidity and mortality in the world. Juglone is a natural compound which has been isolated from Juglans mandshurica Maxim, and it has various pharmacological effects such as antiviral, antibacterial, and anticancer. In our study, we aimed to investigate the effect of juglone on CCL-228-SW 480 colon carcinoma cell line in monolayer and spheroid culture medium. Materials and Methods: The CCL-228-SW 480 cell lines were cultured in both monolayer and spheroid cultures. Cells were treated with juglone at 24, 48, and 72 h of incubation. ID50 inhibition was determined on the dose for juglone and after it was found 20 μM was applied to the cells to examine the effect of juglone on CCL-228-SW 480 colon carcinoma cell line. After Juglone was applied the BrdU marking index, Transferase dUTP Nick ends Labeling (TUNEL) assay, active caspase-3 assay, apoptosis-inducing factor (AIF) assay were determined by immunohistochemistry in both the monolayer and spheroid cultures. Results: The control group had a healthy pattern of S-phase fraction, and many of the CCL-228-SW 480 cells nuclei were observed to be positive for BrdU. Terminal Deoxynucleotidyl TUNEL-positive cells, active Caspase-3, and AIF were detected after treatment with juglone in both the monolayer and spheroid cultures. Conclusions: The dead cell count was higher in the CCL-228-SW 480 cell lines with juglone applied than in the controls. Juglone significantly inhibits the proliferation and induces the apoptosis of CCL-228-SW 480 cells in vitro.

© 2021 Wiley Periodicals LLC.Apoptotic effects of secoisolariciresinol diglucoside (SDG) in 2D and 3D cultures of SW480 cells were investigated. 40–200 μM SDG was used and IC50 values were determined for three different time intervals as 24, 48, or 72 hr for further experiments. BrdU, TUNEL, AIF, and caspase-3 stainings were used. SDG inhibited cell proliferation almost half and half for all time intervals in 2D and 3D cultures and also, induced apoptosis. Apoptotic cell percentages in the control group for 24, 48, and 72 hr were 27.00%, 29.00%, and 28.00%, respectively, while in the SDG treatment group were 59.00%, 61.00%, and 62.00%, respectively. In the spheroid cell culture, apoptotic cell percentages in the control group for 24, 48, and 72 hr were 6.90%, 7.20%, and 7.10%, respectively, while in the SDG treatment group were 19.50%, 19.50%, and 20.70%, respectively. Caspase-3 and AIF antibodies were used to indicate caspase-dependent and -independent apoptotic pathways. Significant increases were seen in both AIF and caspase-3 stainings when compared to the control group but caspase-3 staining results were significantly greater when compared to the AIF staining at all time intervals (p

Cyprodinil and thiacloprid are two of the most commonly used pesticides in Turkey. It is more likely to reach humans or animals due to their widespread use. This study aims to investigate whether there is a DNA damage risk due to cyprodinil and thiacloprid exposure. Zebrafish, which is used as a model organism in health and environmental research, and comet assay were chosen to demonstrate this damage. Ten zebrafish per group were exposed to 2 different concentrations for each pesticides (0.31 and 0.155 mg/L for cyprodinil and 1.64 and 0.82 mg/L for thiacloprid) for 21 days. After, gills were excised and comet assay was performed. Photos of an average of 50 cells per slide were taken and were analyzed with visual evaluation program. DNA damage was found to be increased in the 0.31 mg/L cyprodinil, 0.82 mg/L thiacloprid, and 1.64 mg/L thiacloprid treatment groups when compared to the control group (p < 0.001). Average tail DNA percentage parameter values were 9.45 +/- 0.51, 10.30 +/- 0.34, 11.17 +/- 0.33, and 2.47 +/- 0.06 respectively. Cyprodinil and thiacloprid were identified as genotoxic agents that should be investigated further.

Background: Quercetin (QCT) is a dietary flavonoid with many beneficial effects (e.g., antioxidant, antiaging, antidiabetic, antifungal effects, and regulation of gastrointestinal motor activity in human); furthermore, it induces apoptosis, cell cycle arrest, and differentiation. Objective: The apoptotic effects of OCT were investigated on SW480 human colon cancer cell lines in monolayer and spheroid cultures. Methods: Quercetin (40–200 μM) was applied, and Inhibitory Concentration (IC50) doses were determined for three time intervals (24, 48, and 72 h). The effective dose was determined and applied for analyses, including staining with BrdU to investigate cell proliferation, terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) to investigate apoptosis, and caspase-3 and Apoptosis Inducing Factor (AIF) to investigate caspase-dependent or independent apoptotic pathways. Results: The effective dose of QCT was determined to be 200 μM and was found to induce apoptosis and inhibit cell proliferation at 24, 48, and 72 h,both in 2D and 3D cultures. Significant increases were observed in both caspase-3 and AIF staining, but cells showed greater caspase-3 staining compared with AIF staining at all time intervals (p Conclusion: The QCT treatment groups showed more cell death and less cell growth compared with the untreated control groups in both 2D and 3D cultures of SW480 cell lines. The results suggest that quercetin induces apoptosis, inhibits cell proliferation, and has a protective role against colon cancer. However, further studies are needed to clarify its mechanism of action.

This study aimed to investigate the effects of juglone on the human bladder carcinoma cell lines TCC-SUB and RT-4 in monolayer and spheroid cultures. Cells were treated with juglone at 24, 48, and 72 h of incubation. The activity of caspase-3 was detected in vitro using a caspase-3 colorimetric assay kit according to the manufacturer's instructions. The bromodeoxyuridine (BrdU) labeling index was used to determine the cells of the synthesis phase. The terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay was used to determine the death of cells in both the monolayer and spheroid cultures. The control group had a large S-phase fraction and many of the TCC-SUB and RT-4 cells nuclei were observed to be positive for BrdU. The dead cell count was higher in the TCC-SUB and RT-4 cell lines with juglone applied than in the controls. We conclude that juglone significantly inhibits the proliferation and induces the apoptosis of TCC-SUB and RT-4 cells in vitro.

Experimental animals: 36 female Wistar-Albino rats which were just weaned with a weight of 150–200 g (4–5 weeks of age) were used in the study. The rats were kept in the light/dark and at room temperature (22–24°C) for 12 hours. Adequate amounts of drinking water and standard rat food were given. The study was conducted in the Experimental Research Center, Biochemistry and Histology Laboratories in accordance with the ethics committee rules for animal experiments after obtaining approval from the Experimental Animals Ethics Committee (24.04.2012-06). Pomegranate juice: The pomegranates were washed and peeled and squeezed by hand each morning. Organization of the experiment groups and conduction of the experiment: Thirty six animals were randomly assigned to the following four groups: Paracetamol group (n=10): 1.5 mL/day distilled water was given by gavage for eight days, paracetamol was given orally at a dose of 3 000 mg/kg on the 8th day, Pomegranate juice + Paracetamol (n=10): 1.5 mL/day pomegranate juice was given by gavage for eight days, paracetamol was given orally at a dose of 3 000 mg/kg on the 8th day. Pomegranate juice group (n=8): 1.5 mL/day pomegranate juice was given orally for eight days, Control group (n=8): 1.5 mL/day distilled water was given orally for eight days. Anesthesia, obtaining tissue and blood samples: On the 9th day, anesthesia was achieved by intraperitoneal ketamine (80 mg/kg) and xylazine (10 mg/kg) before sacrifice and a 4–6 mL blood sample was obtained from the aorta with sterile injector. The blood samples were centrifuged at 5 000 RPM for 5 minutes and their sera were separated. At the end of the study, the abdomen was cut in the midline and the right lobe of the liver was removed for histological examination. Measurement of lipid peroxidation (TBARS): Lipid peroxidation was studied in serum and hepatic tissue by way of colorimetric measurement method. Malondialdehide and tiobarbituric acid (TBA) complex is formed with interaction of MDA and TBA at high temperature and colorimetric measurement is performed in an acidic environment. TBARS concentrations of the samples were calculated by way of standard-absorbance graphic. The results were given as μM/mL in serum and as μM/g protein in hepatic tissue. Histopathological examination: The tissues were fixed in 10% neutral formaldehyde solution and paraffin blocks were prepared. Five-micron-thick sections were obtained from the paraffin blocks prepared. The samples were stained with hematoxylin-eosine for histological evaluation. The samples which were stained were examined with Olympus BX50 binocular microscope. The hepatic sections were examined by a single histologist who was blind to the study groups and scoring was performed. The hepatic tissues were examined in terms of increase in connective tissue, granular degeneration, mononuclear cell infiltration, necrotic cells and vascular congestion. The severity of each finding was scored as 0 (normal), +1 (mild), 2++ (moderate) +++ 3 (severe) according to the study of Yahya et al. (23). Afterwards, the total scores of the groups were compared.

Non-alcoholic Fatty Liver Disease (NAFLD) includes a wide range of diseases from simple fatty liver to steatohepatitis, fibrosis and cirrhosis. Alcoholic fatty liver disease and its more serious form, NAFLD, are related mostly to obesity and insulin resistance. Adipokines, secreted form fatty tissues, increases with weight gain and body-mass index (BMI). Previous studies showed that most adipokines increased with liver steatosis but changes of visfatin and IL-6 levels are still controversial. We applied a high dose fructose diet to mice via adding 30% w/v fructose to the drinking water for 4-6 weeks. High levels of liver damage and NAFLD were observed within the experiment group. Visfatin and IL-6 levels were also evaluated using immunohistochemistry. We found high levels of liver damage in fructose group along with increased levels of biochemical liver damage markers. Both IL-6 and visfatin staining were observed higher in the fructose group. Our study suggests that the IL-6 and visfatin levels were increased with obesity and liver damage. We aimed that this study will create an opportunity for new research with IL-6 and visfatin.

Amaç: Fosfatlı gübrelerde, deterjanlarda ve rafine petrol türevlerinde bulunan kadmiyum, 1817 yılında keşfedilmiş toksik ağır bir metaldir ve sigaranın majör bileşenlerinden biridir. Selenyum serbest radikallerin üretimini azaltmak ve önlemek için gerekli olan, doymamış yağ asitlerinden türeyen ve peroksitleri yok ettiği düşünülen bir elementtir. Melatonin, pineal bezin majör hormonudur. Organizma, serbest radikallerin neden olduğu hücre hasarını önlemek için antioksidan savunma sistemi geliştirir. Bu çalışmada, kadmiyumun vücutta dokularda birikerek oluşturduğu toksisite üzerine Selenyum (Se) ve Melatoninin etkisinin belirlenmesi amaçlandı. Gereç-Yöntem: Deney grupları; her grupta 8 dişi sıçan olmak üzere, kontrol (Grup I), Kadmiyum (Grup II), Melatonin (Grup III), Selenyum (Grup IV), Kadmiyum+Melatonin (Grup V), Kadmiyum+Selenyum (Grup VI), Melatonin+Selenyum (Grup VII) ve Kadmiyum+Melatonin+Selenyum (Grup VIII) şeklinde düzenlendi. Kadmiyum (2 mg/kg/gün; gavajla), Melatonin (3 mg/kg/gün; intraperitoneal) 30 gün boyunca günde bir kez, selenyum ise 5'er gün arayla 30 günde 6 kez uygulandı. Deney sonunda over, tuba uterina ve uterus dokuları alınarak, bir kısmı histokimyasal ve immünohistokimyasal değerlendirme için %10'luk nötral formaldehit içerisine, diğer kısmı ise biyokimyasal çalışma için fosfat tamponu içerisine ve kan örnekleri apopitotik hücre ve DNA fragmantasyonu tayini için EDTA'lı tüplere alındı. Bulgular, Sonuç ve Tartışma: Çalışmamızın sonunda kadmiyum verilmesine bağlı olarak over, tuba uterina ve uterus dokularında MDA düzeyleri kontrol grubuna göre artış gözlendi. GSPx ve CAT aktivite değerlerinde de artış saptandı. Grup III, VII ve VIII' de benzer parametreler gözlendi. Grup V ve VI' da ise antioksidanların etkisi ile lipid peroksidasyon engellenerek MDA, GSPx ve CAT düzeylerinin kadmiyuma göre düştüğü tespit edildi. DNA ladder kit ile yapılan analizler sonucunda sadece kadmiyum verilen grupta DNA fragmantasyonu ve buna bağlı olarak apopitotik hücre artışı gözlendi. Histolojik ve immünohistokimyasal bulgularımızda biyokimyasal analizler ve DNA ladder değerlerine paralel sonuçlar elde edildi. Kadmiyum grubunun bütün dokularında hasar (overlerin foliküllerinde dejenerasyon, hemorajik alanlar, mononükleer hücre infiltrasyonu ve bağ dokusu artışı; tuba uterina'nın epitelinde dejenerasyon ve tübüllerinde dejenerasyon; uterusun epitelinde dejenerasyon, endometriyum tabakasında dilate alanlar ve endometriyal bezlerde dejenerasyon), E-kaderin, NCAM sentezinde artış ve dokularda yüksek MT-3 birikimi gözlendi. Grup VI ve VIII' de anlamlı histopatolojik düzelmeler gözlemlendi, ancak grup V'te herhangi bir düzelme tespit edilemedi. Kadmiyumun dişi genital sistem organlarında hasar meydana getirdiğini, selenyumun dokuları bu hasardan korurken Melatoninin herhangi bir koruyucu ya da düzeltici etkisi olmadığı gözlendi. Melatoninin koruyucu bir etki gösterememesinin sebebini dişi sıçanların hormonal değişimlerine ve Melatoninin uzun süreli kullanımına bağlı olabileceği düşünüldü. Çalışmamızın kadmiyum tedavisine ya da korumasına katkı sağlamasını ve yeni tedavi yollarına basamak teşkil etmesini umuyoruz. Aim: Cadmium which is discovered in 1817 is a toxic heavy metal and found in phosphate fertilizers, detergents and refined petroleum and it's one of the major components of cigarette smoking. Selenium is an element, derived from unsaturated fatty acids, thought to degrade peroxides and needed to reduce - prevent the production of free radicals. Melatonin is the major hormone of the pineal gland and it is develops an antioxidant defense system to prevent cell damage caused by free radicals in organism. In our study, it was aimed to determine whether Selenium and Melatonin show antioxidant properties on the toxicity that cadmium accumulates on tissues in the body. Material Method: Experimental groups; Control (Group I), Cadmium (Cd) (Group II), Melatonin (Group III), Selenium (Group IV), Cadmium+Melatonin (Group V), Cadmium+Selenium (Group VI), Melatonin+Selenium (Group VII) and Cadmium + Melatonin + Selenium (Group VIII) were arranged to be8 female rats in each group. Cadmium (2 mg / kg / daywith gavage), Melatonin (3 mg / kg / day, intraperitoneal)30 days were applied once a day and seleneium wasapplied 6 times in 30 days, 5 days a day. At the end ofthe experiment, over, tuba uterine and uterus tissues weretaken. Some of the receiving tissues were in 10% neutralformaldehyde for histochemical and immunohistochemicalevaluation and the other were in phosphate buffer forbiochemical study and bloods were taken into the EDTAtube for apoptotic cell and DNA fragmentation assay.Results and Discussion: At the end of our study, MDAlevels were increased in the over, tubal uterine anduterine tissues according to the cadmium administrationgroup and also increase in GSPx and CAT activity valueswas detected, similar parameters were also observed ingroup III, group VII, group VIII. But in group V and groupVI, were found to inhibit lipid peroxidation of antioxidantsand decrease MDA, GSPx and CAT levels comparedto cadmium. As a result of the analysis with DNA ladderkit, DNA fragmentation and consequently apoptotic cellsnumber were observed only in the cadmium-administeredgroup. Histological and immunohistochemical findingsgave parallel results to biochemical analyzes and DNAladder values. in all the tissues of the cadmium group were observed; High MT-3 accumulation, damage (degeneration of ovarian follicles, haemorrhagic areas, mononuclear cell infiltration and increased connective tissue; degeneration in tuba uterina epithelium and degeneration in tubules; degeneration in the uterine epithelium, dilate fields in the endometrium layer and degeneration in the endometrial glands) and increase in E-cadherin, NCAM synthesis. When significant improvements were observed in group VI and group VIII, there were no improvement in the group V. We have seen that cadmium brings damage to the female genital system organs and while selenium has protective effect for tissues from this damage, Melatonin has not a protective or corrective effect but we think, the cause of this event because of to hormonal changes of female rats and the long-term use of Melatonin. At last, we hope that our work will contribute to cadmium treatment or protection and will provide a stepping stone to new ways of treatment.

Background: Silibinin is a bioactive flavonolignan extracted from milk thistle, known as Silybum marianum. Silibinin exerts strong antiproliferative, proapoptotic, and anti-inflammatory effects. Many studies have shown that silibinin inhibits experimentally induced malignancies of the liver, prostate, skin, and colon as well as promotes inhibition of the proliferation of cancer cell lines in vitro. This study aimed to investigate the effects of silibinin on the human breast carcinoma cell lines MDA-MB-231 and MCF-7 in monolayer and spheroid cultures. Method: The MDA-MB-231 and MCF-7 cell lines were cultured in both monolayer and spheroid cultures. Cells were treated with silibinin at 24, 48, and 72 h of incubation. The 5-bromo-2′-deoxyuridine labeling index was used to determine the cells of the synthesis phase. Poly-ADP-ribose-polimerase immunohistochemical staining and the terminal deoxynucleotidyl transferase dUTP nick and labeling assay were used to determine the death of cells in both the monolayer and spheroid cultures. Results: An half maximal inhibitory concentration dose of silibinin in MDA-MB-231 and MCF-7 cells was 100 µM/mL at 24, 48, and 72 h of incubation. Terminal deoxynucleotidyl transferase dUTP nick and labeling positive cells and active poly-ADP-ribose-polimerase were detected after treatment with silibinin in both the monolayer and spheroid cultures. The dead cell count was higher in the MDA-MB-231 and MCF-7 cell lines with silibinin applied than in the controls. Conclusions: Our study demonstrated that silibinin applications enhanced terminal deoxynucleotidyl transferase dUTP nick and labeling positive cells and active poly-ADP-ribose-polimerase in comparison to the control in both the monolayer and spheroid cultures.

Background/aim: To investigate the efficiency of Capparis ovata as a protective agent against acute paracetamol toxicity of the liver. Materials and methods: A total of 36 Wistar albino rats were divided into 4 groups: 1) paracetamol, 2) Capparis ovata + paracetamol, 3) Capparis ovata, and 4) control. Groups 2 and 3 were given Capparis ovata and Groups 1 and 4 distilled water for 8 days. On day 8, 3000 mg kg-1 paracetamol was administered orally to Groups 1 and 2. Samples were taken on day 9. AST, ALT, total bilirubin, direct bilirubin, GGT, and ALP levels were assessed. Lipid peroxidation markers and thiobarbituric acid-reactive substance (TBARS) levels were measured in the blood and liver. Liver tissues were evaluated histologically. Results: AST, ALT, and total bilirubin levels were lower in Group 2 than in Group 1 (P < 0.05). TBARS levels were lower in Groups 2 (P = 0.000), 3 (P = 0.001), and 4 (P = 0.001) than in Group 1. Degenerative findings were lower in the Capparis ovata + paracetamol group than in the paracetamol group (P < 0.05). Conclusion: It can be concluded that Capparis ovata has a protective effect on the liver, both histopathologically and biochemically, against paracetamol-induced liver injury.

WOS: 000376564200036 A previously healthy 55-year-old man with right sided lateral chest pain admitted to clinic. It was found a solid and painful mass at the right 4th rib in physical examination. Chest X-ray and thoracic computarized tomography showed an opacity measured 60x33 mm within the right chest wall destructing the 4th rib. Needle aspiration was performed from tumor and cytologic examination showed atypic plasma cell infiltration. The patient was scheduled for a chest wall resection and reconstructive surgery. Examination of a permanent section showed that the chest wall tumor was solitary plasmacytoma. There was no evidence of multiple myeloma recurrence after two years from the operation.