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Lycium barbarum (goji berry) has long been used as a food and traditional herbal medicine. This study aimed to investigate the beneficial effect of the goji berry on dry eye disease in rats. Male Sprague-Dawley rats with induced dry eye disease were randomly assigned to four groups: Vehicle (control), low-dose goji berry extract [GBE; 250 mg/kg/body weight (bw)], median-dose GBE (350 mg/kg/bw), and high-dose GBE (500 mg/kg/bw). Three methods, Schirmer's test, tear break-up time (BUT) measurement and keratoconjunctival fluorescein staining, were used to evaluate the effect of GBE on symptoms of dry eye disease experienced by the rats. The results of the present study revealed that both the Schirmer's test score and tear BUT significantly increased following 1 week of GBE administration. Furthermore, the severity of the keratoconjunctival staining decreased significantly. In addition, the results suggested that administration of GBE may ameliorate dry eye disease symptoms in a dose-dependent manner. There were no mortalities and no apparent abnormal histopathology changes in the liver or kidney tissues of rats administered GBE for 21 consecutive days. Polysaccharides and betaine present in GBE may have important effects in alleviating dry eye disease induced by oxidative stress and inflammation. In conclusion, the goji berry is a safe, functional food with beneficial effects in alleviating dry eye disease. [ABSTRACT FROM AUTHOR]

Geniposide and genipin have been found in Gardenia jasminoides Ellis, a traditional Chinese medicine that exhibits multiple biological functions. However, no report showing the effects of geniposide and genipin on gastric protection in Helicobacter pylori infections in vitro and in vivo has been done. In this study, we clarified how geniposide and genipin suppress H. pylori-mediated inflammation in gastric AGS cells and C57BL/6 mice. Our results demonstrated that genipin shows a strong ability to inhibit H. pylori growth and is able to reduce vacA and cagA gene expression of H. pylori in infected AGS cells. Genipin also attenuates the abilities of adhesion and invasion of H. pylori to AGS cells. An attenuation of interleukin (IL)-8 and IFN-γ production caused by genipin was observed to inhibit cell inflammatory responses. In the in vivo experiments, geniposide and genipin both showed suppressive effects on the vacA gene expression in mice after H. pylori infection. The serum levels of IFN-γ, IL-1β, immunoglobulin A, and Immunoglobulin M were decreased by geniposide and genipin in infected mice. The inflammatory maker COX2 was downregulated in H. pylori-infected mice after exposure to geniposide and genipin. Together, geniposide and genipin effectively exert a healthy promotion to reduce H. pylori infections in vivo by interfering with the growth and virulence of H. pylori as well as attenuating the gastric inflammation caused by an H. pylori infection. Practical Application Geniposide and genipin have a healthy promotion to eradicate H. pylori infections by interfering with the growth and virulence of H. pylori and to attenuate the gastric inflammation caused by an H. pylori infection. [ABSTRACT FROM AUTHOR]

Epigallocatechin gallate (EGCG) is a green tea polyphenol that presents anticancer activities in multiple cancer cells, but no available report was addressed for the underling molecular mechanism of cytotoxic impacts on drug-resistant oral squamous cell carcinoma cells. In the present study, the inhibitory effects of EGCG were experienced on cisplatin-resistant oral cancer CAR cells. EGCG inhibited cell viability in a time- and concentration-dependent manner by a sulforhodamine B (SRB) assay. EGCG induced CAR cell apoptosis and autophagy by 4′,6-diamidino-2-phenylindole (DAPI) dye, acridine orange (AO) staining and green fluorescent protein (GFP)-tagged LC3B assay, respectively. EGCG also significantly enhanced caspase-9 and caspase-3 activities by caspase activity assay. EGCG markedly increased the protein levels of Bax, cleaved caspase-9, cleaved caspase-3, Atg5, Atg7, Atg12, Beclin-1, and LC3B-II, as well as significantly decreased the expression of Bcl-2, phosphorylated AKT (Ser473) and phosphorylation of STAT3 on Tyr705 by western blotting in CAR cells. Importantly, the protein and gene expression of multidrug resistance 1 (MDR1) were dose-dependently inhibited by EGCG. Overall, downregulation of MDR1 levels and alterations of AKT/STAT3 signaling contributed to EGCG-induced apoptosis and autophagy in CAR cells. Based on these results, EGCG has the potential for therapeutic effect on oral cancer and may be useful for long-term oral cancer prevention in the future. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 845-855, 2017. [ABSTRACT FROM AUTHOR]

The article presents a list of reviewers of the journal including Koushik Adhikari, Kadri Koppel and Robert Tyler.

ABSTRACT Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist and lipid-lowering agent, has been used worldwide for treatment of hyperlipidemia. The clinical trials demonstrate that fenofibrate possesses multiple pharmacological activities, including antitumor effects. However, the precise mechanisms in oral squamous cell carcinoma (OSCC) remain unclear. In this study, we investigated the anticancer effects of fenofibrate on the migration and invasion of human oral cancer CAL 27 cells. Fenofibrate inhibited the cell migration and invasion of CAL 27 cells by the wound healing and Boyden chamber transwell assays, respectively. In addition, fenofibrate reduced the protein expressions of MMP-1, MMP-2, MMP-7, and MMP-9 by Western blotting and inhibited enzyme activities of MMP-2/-9 using gelatin zymography assay. Results from immunoblotting analysis showed that the proteins of p-LKB1 (Ser428), LKB1, p-AMPKα (Thr172), p-AMPKα1/α2 (Ser425/Ser491), p-AMPKβ1 (Ser108), and AMPKγ1 were upregulated by fenofibrate; the levels of p-IKKα/β (Ser176) and p-IκBα were reduced in fenofibrate-treated cells. Also, fenofibrate suppressed the expressions of nuclear NF-κB p65 and p50 by immunoblotting and NF-κB DNA binding activity by EMSA assay. The anti-invasive effect of fenofibrate was attenuated by compound C [an adenosine 5′-monophosphate-activated protein kinase (AMPK) inhibitor] or dominant negative form of AMPK (DN-AMPKα1). Thus, fenofibrate considerably inhibited metastatic behaviors of CAL 27 cells might be mediated through blocking NF-κB signaling, resulting in the inhibition of MMPs; these effects were AMPK-dependent rather than PPARα signaling. Our findings provide a molecular rationale, whereby fenofibrate exerts anticancer effects and additional beneficial effects for the treatment of cancer patients. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 866-876, 2016. [ABSTRACT FROM AUTHOR]

Casticin, a polymethoxyflavone occurring in natural plants, has been shown to have anticancer activities. In the present study, we aims to investigate the anti-skin cancer activity of casticin on melanoma cells in vitro and the antitumor effect of casticin on human melanoma xenografts in nu/nu mice in vivo. A flow cytometric assay was performed to detect expression of viable cells, cell cycles, reactive oxygen species production, levels of and caspase activity. A Western blotting assay and confocal laser microscope examination were performed to detect expression of protein levels. In the in vitro studies, we found that casticin induced morphological cell changes and DNA condensation and damage, decreased the total viable cells, and induced G2/M phase arrest. Casticin promoted reactive oxygen species (ROS) production, decreased the level of , and promoted caspase-3 activities in A375.S2 cells. The induced G2/M phase arrest indicated by the Western blotting assay showed that casticin promoted the expression of p53, p21 and CHK-1 proteins and inhibited the protein levels of Cdc25c, CDK-1, Cyclin A and B. The casticin-induced apoptosis indicated that casticin promoted pro-apoptotic proteins but inhibited anti-apoptotic proteins. These findings also were confirmed by the fact that casticin promoted the release of AIF and Endo G from mitochondria to cytosol. An electrophoretic mobility shift assay (EMSA) assay showed that casticin inhibited the NF-B binding DNA and that these effects were time-dependent. In the in vivo studies, results from immuno-deficient nu/nu mice bearing the A375.S2 tumor xenograft indicated that casticin significantly suppressed tumor growth based on tumor size and weight decreases. Early G2/M arrest and mitochondria-dependent signaling contributed to the apoptotic A375.S2 cell demise induced by casticin. In in vivo experiments, A375.S2 also efficaciously suppressed tumor volume in a xenotransplantation model. Therefore, casticin might be a potential therapeutic agent for the treatment of skin cancer in the future. [ABSTRACT FROM AUTHOR]

Arsenic trioxide is an old drug and has been used for a long time in traditional Chinese and Western medicines. However, the cancer treatment of arsenic trioxide has heart and vascular toxicity. The cytotoxic effects of arsenic trioxide and its molecular mechanism in human umbilical mesenchymal stem cells (HUMSC) and human bone marrow-derived mesenchymal stem cells (HMSC-bm) were investigated in this study. Our results showed that arsenic trioxide significantly reduced the viability of HUMSC and HMSC-bm in a concentration- and time-dependent manner. Arsenic trioxide is able to induce apoptotic cell death in HUMSC and HMSC-bm, as shown from the results of morphological examination, flow cytometric analyses, DAPI staining and comet assay. The appearance of arsenic trioxide also led to an increase of intracellular free calcium (Ca2+) concentration and the disruption of mitochondrial membrane potential (ΔΨm). The caspase-9 and caspase-3 activities were time-dependently increased in arsenic trioxide-treated HUMSC and HMSC-bm. In addition, the proteomic analysis and DNA microarray were carried out to investigate the expression level changes of genes and proteins affected by arsenic trioxide treatment in HUMSC. Our results suggest that arsenic trioxide induces a prompt induction of ER stress and mitochondria-modulated apoptosis in HUMSC and HMSC-bm. A framework was proposed for the effect of arsenic trioxide cytotoxicity by targeting ER stress. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 314-328, 2016. [ABSTRACT FROM AUTHOR]

ABSTRACT The authors' previous study has shown that water extract of Hedyotis diffusa Willd (HDW) promoted immune response and exhibited anti-leukemic activity in BALB/c leukemic mice in vivo. In this study, the anti-proliferation effects of ethanol extract of H. diffusa Willd (EEHDW) on lung cancer cell lines (A549, H1355, and LLC), leukemia cell lines (HL-60, WEHI-3), and a mouse melanoma cell line (B16F10) in vitro were investigated. The results demonstrated that EEHDW suppressed the cell proliferation of A549, H1355, HL-60, WEHI-3, and B16F10 cells as well as reduced cell viability in a concentration-dependent manner. We found that EEHDW inhibited the cell proliferation of HL-60 cells in concentration-dependent manner. In addition, EEHDW triggered an arrest of HL-60 cells at G0/G1 phase and sub-G1 population (apoptotic cells). EEHDW provoked DNA condensation and DNA damage in HL-60 cells. The activities of caspase-3, caspase-8, and caspase-9 were elevated in EEHDW-treated HL-60 cells. DNA microarray to investigate and display the gene levels related to cell growth, signal transduction, apoptosis, cell adhesion, cell cycle, DNA damage and repair, transcription and translation was also used. These findings suggest that EEHDW may be a potential herbal medicine and therapeutic agent for the treatment of leukemia. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1162-1177, 2015. [ABSTRACT FROM AUTHOR]

ABSTRACT Irinotecan HCl (CPT-11) is an anticancer prodrug, but there is no available information addressing CPT-11-inhibited leukemia cells in in vitro and in vivo studies. Therefore, we investigated the cytotoxic effects of CPT-11 in promyelocytic leukemia HL-60 cells and in vivo and tumor growth in a leukemia xenograft model. Effects of CPT-11 on HL-60 cells were determined using flow cytometry, immunofluorescence staining, comet assay, real-time PCR, and Western blotting. CPT-11 demonstrated a dose- and time-dependent inhibition of cell growth, induction of apoptosis, and cell-cycle arrest at G0/G1 phase in HL-60 cells. CPT-11 promoted the release of AIF from mitochondria and its translocation to the nucleus. Bid, Bax, Apaf-1, caspase-9, AIF, Endo G, caspase-12, ATF-6b, Grp78, CDK2, Chk2, and cyclin D were all significantly upregulated and Bcl-2 was down-regulated by CPT-11 in HL-60 cells. Induction of cell-cycle arrest by CPT-11 was associated with changes in expression of key cell-cycle regulators such as CDK2, Chk2, and cyclin D in HL-60 cells. To test whether CPT-11 could augment antitumor activity in vivo, athymic BALB/c nu/nu nude mice were inoculated with HL-60 cells, followed by treatment with either CPT-11. The treatments significantly inhibited tumor growth and reduced tumor weight and volume in the HL-60 xenograft mice. The present study demonstrates the schedule-dependent antileukemia effect of CPT-11 using both in vitro and in vivo models. CPT-11 could potentially be a promising agent for the treatment of promyelocytic leukemia and requires further investigation. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 803-815, 2015. [ABSTRACT FROM AUTHOR]

Many anticancer drugs are obtained from phytochemicals and natural products. However, some phytochemicals have mutagenic effects. Safrole, a component of Piper betle inflorescence, has been reported to be a carcinogen. We have previously reported that safrole induced apoptosis in human oral cancer cells in vitro and inhibited the human oral tumor xenograft growth in vivo. Until now, there is no information addressing if safrole promotes immune responses in vivo. To evaluate whether safrole modulated immune function, BALB/c mice were intraperitoneally injected with murine myelomonocytic WEHI-3 leukemia cells to establish leukemia and then were treated with or without safrole at 4 and 16 mg/kg. Animals were sacrificed after 2 weeks post-treatment with safrole for examining the immune cell populations, phagocytosis of macrophages and the natural killer (NK) cells' cytotoxicity. Results indicated that safrole increased the body weight, and decreased the weights of spleen and liver in leukemic mice. Furthermore, safrole promoted the activities of macrophages phagocytosis and NK cells' cytotoxicity in leukemic mice when compared with untreated leukemic mice. After determining the cell marker population, we found that safrole promoted the levels of CD3 (T cells), CD19 (B cells) and Mac-3 (macrophages), but it did not affect CD11b (monocytes) in leukemic mice. In conclusion, safrole altered the immune modulation and inhibited the leukemia WEHI-3 cells in vivo. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28:601-608, 2013. [ABSTRACT FROM AUTHOR]

Our earlier studies have demonstrated that gallic acid (GA) induced cytotoxic effects including induction of apoptosis and DNA damage and inhibited the cell migration and invasion in human cancer cells. However, GA-affected DNA damage and repair gene expressions in human prostate cancer cells are still unclear. In this study, we investigated whether or not GA induces DNA damage and inhibits DNA repair gene expression in a human prostate cancer cell line (PC-3). The results from flow cytometric assay indicated that GA decreased the percentage of viable PC-3 cells in a dose- and time-dependent manner. PC-3 cells after exposure to different doses (50, 100, and 200 μM) of GA and various periods of time (12, 24, and 48 h) led to a longer DNA migration smear (comet tail) occurred based on the single cell gel electrophoresis (comet assay). These observations indicated that GA-induced DNA damage in PC-3 cells, which also confirmed by 4,6-diamidino-2-phenylindole dihydrochloride staining and DNA agarose gel electrophoresis. Alternatively, results from real-time polymerase chain reaction assay also indicated that GA inhibited ataxia telangiectasia mutated, ataxia-telangiectasia and Rad3-related, O6-methylguanine-DNA methyltransferase, DNA-dependent serine/threonine protein kinase, and p53 mRNA expressions in PC-3 cells. Taken together, the present study showed that GA caused DNA damage and inhibited DNA repair genes as well as both effects may be the critical factors for GA-inhibited growth of PC-3 cells in vitro. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 579-587, 2013. [ABSTRACT FROM AUTHOR]

Antrodia camphorata has been recognized to be a traditional Chinese medicine for abdominal pain, diarrhea, and to protect against hepatitis virus infection. Several ingredients derived from A. camphorata possess various pharmacological and biological activities such as antioxidant and anticancer. In this study, its ability to promote immune responses and to exhibited antileukemia activity in WEHI-3 leukemia BALB/c mice were investigated. The results indicated A. camphorata significantly prolonged the survival rate and prevented the body weight loss in leukemia mice. Four mg/kg of A. camphorata treatment significantly decreased the weight of the spleen. Both doses (2 and 4 mg/kg) of A. camphorata did not affect Mac-3 marker in leukocytes. However, the 4 mg/kg of A. camphorata decreased the levels of CD11b and both doses of treatment increased CD3 and CD19. With lipopolysaccharide stimulation, the 4 mg/kg of A. camphorata promoted the significant proliferation of leukocytes; but with concanavalin A stimulation, both doses promoted the significant proliferation of leukocytes. YAC-1 target cells were killed by NK cells from the mice after treatment with A. camphorata at 4 mg/kg in target cells at a ratio of 50:1. The percentage of macrophages with phagocyted at A. camphorata treatment increased, and these effects were in dose-dependent manners. [ABSTRACT FROM AUTHOR]

In this study, we investigated the effects of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one (CHM-1) on cell viability, cell cycle arrest and apoptosis in CT-26 murine colorectal adenocarcinoma cells. For determining cell viability, the MTT assay was used. CHM-1 promoted G2/M arrest by PI staining and flow cytometric analysis. Apoptotic cells were evaluated by DAPI staining. We used CDK1 kinase assay, Western blot analysis and caspase activity assays for examining the CDK1 activity and proteins correlated with apoptosis and cell cycle arrest. The in vivo anti-tumor effects of CHM-1-P were evaluated in BALB/c mice inoculated with CT-26 cells orthotopic model. CHM-1 induced CT-26 cell viability inhibition and morphologic changes in a dose-dependent and time-dependent manner and the approximate IC50 was 742.36 nM. CHM-1 induced significant G2/M arrest and apoptosis in CT-26 cells. CHM-1 inhibited the CDK1 activity and decreased CDK1, Cyclin A, Cyclin B protein levels. CHM-1 induced apoptosis in CT-26 cells and promoted increasing of cytosolic cytochrome c, AIF, Bax, BAD, cleavage of pro-caspase-9, and -3. The significant reduction of caspase-9 and -3 activity and increasing the viable CT-26 cells after pretreated with caspase-9 and -3 inhibitor indicated that CHM-1-induced apoptosis was mainly mediated a mitochondria-dependent pathway. CHM-1-P improved mice survival rate, and enlargement of the spleen and liver metastasis were significantly reduced in groups treated with either 10 mg/kg and 30 mg/kg of CHM-1-P and 5-FU in comparison to these of CT-26/BALB/c mice. Taken together, CHM-1 acted against colorectal adenocarcinoma cells in vitro via G2/M arrest and apoptosis, and CHM-1-P inhibited tumor growth in vivo. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat inflammation and pain and even to prevent the progression of cardiovascular disease. They have become widely used because of their effectiveness, especially among athletes performing high-intensity training. Indomethacin is used for pain management in sports medicine and is highly effective and versatile. However, several clinical studies have reported that indomethacin induces acute renal damage. In the present study, we determined that indomethacin reduced human embryonic kidney 293 (HEK293) cell viability in a concentration-dependent manner by triggering apoptosis. In addition, we demonstrated the effect of quercetin on indomethacin-treated HEK293 cells by inactivating the caspase-3 and caspase-9 signals. Furthermore, quercetin reduced ROS production and increased mitochondrial membrane potential (ΔΨm) in indomethacin-treated HEK293 cells. Our results indicate that quercetin can interrupt the activated caspase and mitochondrial pathway induced by indomethacin in HEK293 cells and affect apoptotic mRNA expression. Quercetin can protect against indomethacin-induced HEK293 cell apoptosis by regulating abnormal ΔΨm and apoptotic mRNA expression. [ABSTRACT FROM AUTHOR]

Dracorhodin can be isolated from the exudates of the fruit of Daemonorops draco. Previous studies suggested that dracorhodin perchlorate can promote fibroblast proliferation and enhance angiogenesis during wound healing. In the present study, the potential bioactivity of dracorhodin perchlorate in human HaCaT keratinocytes, were investigated in vitro, with specific focus on HaCaT wound healing. The results of in vitro scratch assay demonstrated the progressive closure of the wound after treatment with dracorhodin perchlorate in a time-dependent manner. An MTT assay and propidium iodide exclusion detected using flow cytometry were used to detect cell viability of HaCaT cells. Potential signaling pathways underlying the effects mediated by dracorhodin perchlorate in HaCaT cells were clarified by western blot analysis and kinase activity assays. Dracorhodin perchlorate significantly increased the protein expression levels of β-catenin and activation of AKT, ERK and p38 in HaCaT cells. In addition, dracorhodin perchlorate did not induce HaCaT cell proliferation but promoted cell migration. Other mechanisms may yet be involved in the dracorhodin perchlorate-induced wound healing process of human keratinocytes. In summary, dracorhodin perchlorate may serve to be a potential molecularly-targeted phytochemical that can improve skin wound healing. [ABSTRACT FROM AUTHOR]

Glucocorticoids are widely used anti-inflammatory drugs in clinical settings. However, they can induce skeletal muscle atrophy by reducing fiber cross-sectional area and myofibrillar protein content. Studies have proven that antioxidants can improve glucocorticoid-induced skeletal muscle atrophy. Quercetin is a potent antioxidant flavonoid widely distributed in fruits and vegetables and has shown protective effects against dexamethasone-induced skeletal muscle atrophy. In this study, we demonstrated that dexamethasone significantly inhibited cell growth and induced cell apoptosis by stimulating hydroxyl free radical production in C2C12 skeletal muscle cells. Our results evidenced that quercetin increased C2C12 skeletal cell viability and exerted antiapoptotic effects on dexamethasone-treated C2C12 cells by regulating mitochondrial membrane potential (ΔΨm) and reducing oxidative species. Quercetin can protect against dexamethasone-induced muscle atrophy by regulating the Bax/Bcl-2 ratio at the protein level and abnormal ΔΨm, which leads to the suppression of apoptosis. [ABSTRACT FROM AUTHOR]

Phenolic compounds gained great interest due to their preventative role against certain diseases such as diabetes, Alzheimer diseases and cancer. Therefore recent studies have focus on the investigation of bioactivity of phenolic compound found in plant. In this study, we aimed to determine the phenolic composition of Gypsophila lepidioides as well as its antioxidant and anti-cancer potentials. Phenolic and flavonoid content of the extracts were determined by Folin ciocalteu method and Aluminium chloride colorimetric method, respectively. In addition, HPLC technique was used to detect the most abundant individual phenolic compounds in G. Lepidioides. In order to determine the antioxidant activity of the species, water and methanolic extracts were prepared and four assay, namely ABTS, DPPH CUPRAC and Fe2+ chelating activity assays, were performed. For anticancer activity, the extracts were tested against three cancerous cell lines namely, human breast carcinoma MCF-7 cells, colorectal carcinoma HT-29 cells and hepato carcinoma HepG2 cells by XTT cell proliferation assays. The result showed that, in parallel to the total phenolic and flavonoid contents, methanolic extract of G. Lepidioides showed higher antioxidant activity, except for CUPRAC assay, as compared to water extract in all antioxidant assays. IC50 (mg/ml) values for methanolic extract of G. Lepidioides were 0,556 mg/ml, 145,79 μg/ml and 0,551 mg/ml for DPPH, ABTS and Fe2+ chelating activity of G. Lepidioides, respectively. HPLC analsysis indicated that the most abundant individual phenolic compounds in water extact of G. Lepidioides are pyrogallol (0,160 μg/g ext.), 3,4- dihidroxybenzoic acid (0,133 μg/g ext.) and phidroxybenzoic acid (0,0086 μg/g ext). Similarly, methanolic extract was found to contain pyrogallol (0,715 μg/g ext.), 3,4- dihidroxybenzoic acid (0,170 μg/g ext.) and p-hydroxybenzoic acid (0,0262 μg/g ext.) as well as vanillin (0,0166 μg/g ext.). Parallel to the antioxidant activity, methanolic extract of G. Lepidioides indicated a better anti proliferative activity against MCF-7, HT-29 and HepG2 cells with IC50 (mg/ml) values of 1,11 mg/ml 0,644 mg/ml and 0,772 mg/ml, respectively. The result of this study suggest that G. Lepidioides has moderate bioactivity with four major phenolic content. [ABSTRACT FROM AUTHOR]

Oleuropein is the most prevalent phenolic component in olive leaves, seed, pulp and peel of unripe olives. Oleuropein's antioxidant potential is mainly related to its ability to improve radical stability through the formation of an intramolecular hydrogen bond between the free hydrogen of the hydroxyl group and its phenoxyl radicals. Indomethacin, one of the most prescribed nonsteroidal anti-inflammatory drug, can cause oxidative damage in gastric tissue. Here, we investigated the anti-oxidative properties of oleuropein in rats with indomethacin induced gastric ulcer. A total of 56 adult male Wistar rats were divided into seven groups of eight animals as follows: control, indomethacin 25 mg/kg, oleuropein 12 mg/kg, lansoprazole 30 mg/kg as well as indomethacin 25 mg/kg with oleuropein 6 mg/kg, oleuropein 12 mg/kg and oleuropein 18 mg/kg. Gastric ulcers were induced by oral administration of indomethacin, after which the differing doses of oleuropein were administered by oral gavage. The efficacy of oleuropein was compared with lansoprazole. Activities of superoxide dismutase, catalase and myeloperoxidase, as well as malondialdehyde and glutathione levels were determined in stomach tissue. Samples of the stomach tissue were also taken for pathological investigations. Histopathological method was used to detect morphological damage. The results showed that 18 mg/kg oleuropein significantly decreased high malondialdehyde level and myeloperoxidase activity, and increased the activity of antioxidant enzymes (with the exception of catalase) in tissue. Tissue damage in the stomachs of the rats correlated with the biochemical and histopathological findings. In conclusion, these results indicated that oleuropein might have a protective effect against indomethacin induced gastric ulcer and oxidative stress in rats. [ABSTRACT FROM AUTHOR]

The table of contents for the March 2017 issue of the journal is presented.

The table of contents for the July 2016 issue of the journal "Environmental Toxicology" is presented.

The table of contents for the March 2016 issue of "Environmental Toxicology" is presented.

Transient Receptor Potential Vanilloid 1 (TRPV1) is the most investigated member of the TRP superfamily of ion channels which is expressed on many different cell types (Benham et al 2002). When TRPV1 is activated, calcium influx takes place and cell-specific intracellular changes occur. The functions of TRPV1 has not been clarified in cancer cells yet (Tominaga et al, 1998; Fernandes et al, 2012). There are few studies examining the relationship between TRPV1 and breast cancer. In this study we investigated the effects of TRPV1 antagonist AMG-9810 on proliferation of liver (4TLM), brain (4TBM) and heart (4THM) metastatic and non-metastatic (67NR) breast carcinoma cells. 67NR, 4TLM, 4TBM and 4THM carcinoma cells were cultured with DMEM-F12 (%5 FBS) (Erin et al, 2013). TRPV1 agonists and antagonists used for cell treatment. Extents of proliferation of the cells were determined with WST-1 test, 72 hours after treatment. TRPV1 agonist capsaicin was effective at inhibiting cell proliferation but antagonists were generally more effective and AMG-9810 was most effective agent. In conclusion, all four breast carcinoma cells responded well to TRPV1 antagonist AMG-9810. Further studies are required to determine the mechanisms of antitumor effects of AMG-9810 under both in-vitro and in-vivo conditions. [ABSTRACT FROM AUTHOR]