Crocetin ameliorative effect on diabetic nephropathy in rats through a decrease in transforming growth factor-ß and an increase in glyoxalase-I activity.

BACKGROUND & AIMS: Glycation, oxidative stress, and inflammation due to the elevation of transforming growth factor-ß1 (TGF-ß1) participate in diabetic nephropathy (DN). Thus, we investigated for the first time the effect of crocetin (Crt) on the renal histopathological parameters, TGF-ß1 and glycation, oxidative stress, as well as inflammatory markers in the DN rat model. METHODS: Forty male Wistar rats were randomly divided into 4 equal groups: normal (N), N + Crt, DN, and DN + Crt. DN was induced in rats with a combination of nephrectomy and streptozotocin. Treated groups received 100 mg/kg of Crt via intraperitoneal injection monthly for 3 months. Different glycation (glycated albumin, glycated LDL, Methylglyoxal, and pentosidine), oxidative stress (advanced oxidation protein products, malondialdehyde, glutathione, and paraoxonase-I (PON-1)), and inflammatory markers (tumor necrosis factor-α, myeloperoxidase, and TGF-ß1), blood glucose, insulin, lipid profile, creatinine in the serum, and proteinuria, as well as the glyoxalase-1 (GLO-1) activity, was determined. RESULTS: Crt decreased renal biochemical (Cre and PU) and histopathological (glomerulosclerosis) renal dysfunction parameters, diverse glycation, oxidative stress, and inflammatory markers in the DN rats. Furthermore, the treatment corrected glycemia, insulin resistance, and dyslipidemia as well as induced the activities of GLO-1 and PON-1. Over and above, the treatment decreased TGF-ß1 in their serum (p > 0.001). CONCLUSIONS: Crocetin improved DN owing to an advantageous effect on metabolic profile. Further, the treatment with a reducing effect on TGF-ß1, oxidative stress, glycation, and inflammation markers along with an increase in Glo-1 activity showed multiple protective effects on kidney tissue.

Inhibitory effects of Ficus carica and Olea europaea on pro-inflammatory cytokines: A review.

Objectives: Ficus carica (fig) and Olea europaea (olive) are valuable nutritional plants that are widely used in diet and traditional medicine. Different parts of the plants such as fruit and leaves contain beneficial compounds with diverse pharmacological properties, among which anti-inflammatory activities are remarkable. The purpose of this review is to discuss the anti-inflammatory effects of F. carica and O. europaea with emphasis on their impact on pivotal pro-inflammatory cytokines including IL-1, IL-6, and TNF-α. Materials and Methods: To prepare the present review, the sites utilized included Scopus, PubMed, Science Direct, and Google Scholar and studied relevant articles from 2000 until 2021. Results: As a result, we observed that most of the compounds in fig and olive including polyphenols, flavonoids, etc., exert their anti-inflammatory effects through inhibiting or decreasing pro-inflammatory cytokines. Moreover, some natural antioxidants are common between these two plants. Conclusion: We suggest that consuming figs and olives simultaneously or alone can be useful in the prevention or treatment of inflammatory diseases.

Protection of CCl4-induced hepatic and renal damage by linalool.

The aim of the current study is to determine the protective and therapeutic effects of linalool against carbon tetrachloride (CCl4)-induced hepatoxicity and nephrotoxicity. Six-week-old male Wistar rats were divided into five groups: Control group (a regular diet); CCl4 group (1 ml/kg dissolved in olive oil, intraperitoneally at 14th day); pretreatment group (25 mg/kg linalool daily + CCl4 14thday); post-treatment group (25 mg/kg linalool 2, 6, 24, and 48 h after the injection of CCl4 at 14th day); and linalool group (25 mg/kg linalool daily, orally). All animals were sacrificed, tissue and blood samples were collected to analysis. Administration of CCl4 resulted in a marked increase in hepatic (aspartate aminotransferase, alanine transaminase, and alkaline phosphatase) and renal (blood urea nitrogen and creatinine) markers. Also, CCl4 resulted in pathological damages, a significant increase in the concentration of malondialdehyde , tumor necrosis factor-alpha, and Interleukin 6 , expression of nuclear factor kappa-light-chain-enhancer of activated B cells and a significant decrease in the levels of serum total protein, serum albumin, and antioxidants. However, in pretreatment and post treatment groups, linalool significantly inhibited CCl4- induced hepatic and nephric damages. These results demonstrate that linalool has protective and therapeutic effects in an in vitro model of CCL4-induced hepatic and nephric damage, proposing linalool as a potential therapeutic agent against chemical and drug induced hepatotoxicity and nephrotoxicity.

The protective effect of cinnamon and ginger hydro-alcoholic extract on carbon tetrachloride-induced testicular damage in rats.

Sexual dysfunction of men is one of the most serious problems in human society. This study aimed to evaluate the protective effect of cinnamon and ginger extract on testicular damages induced by carbon tetrachloride (CCl4). Thirty-six male Wistar rats were randomly divided into 6 groups (n = 6): 1. Normal control; 2. Carbon tetrachloride (CCl4); 3. CCl4 + Cinnamon; 4. CCl4 + Ginger; 5. CCl4 + Cinnamon and Ginger; and 6. Cinnamon + Ginger. CCl4 (1 ml/kg) was injected intraperitoneally on the 14th day, and cinnamon (50 mg/kg, orally) and ginger (250 mg/kg, orally) were administered daily for 14 days. Fifty hours after the CCl4 injection, the testicles and epididymis were separated and examined as to histological alterations and oxidative stress markers. CCl4 significantly increased malondialdehyde level and decreased total antioxidant capacity when compared to the normal control group (p < .05). In addition, degenerative alterations in the testicular and epididymal tissue were observed in CCl4 group. The pre-treatment with ginger and cinnamon extract significantly improved these parameters when compared to the CCl4 group (p < .05). The results of this study indicated that co-treatment of ginger and cinnamon reduces the damages induced by CCl4 in testicular tissue by increasing antioxidant capacity and reducing lipid peroxidation.

2,4-D causes oxidative stress induction and apoptosis in human dental pulp stem cells (hDPSCs).

2,4-Dicholorophenoxy acetic acid (2,4-D) is a worldwide used hormone herbicide. Human dental pulp stem cells (hDPSCs) as a potential source of mesenchymal stem cells provide a confident model system for the assessments of chemicals in vitro. The main objective of this study was to examine the biological effects and damages attributed to 2,4-D on hDPSCs. hDPSCs were isolated from third molar pulp tissues and their mesenchymal identity were evaluated. Then, hDPSCs were treated with increasing concentrations of 2,4-D (0.1 µM-10 mM). Cell viability assay and cumulative cell counting were carried out to address 2,4-D effects on biological parameters of hDPSCs. Cell cycle distribution, ROS level and ALP activity were measured before and after treatment. AO/EB staining and caspase 3/7 activity were investigated to detect the possible mechanisms of cell death. Flow-cytometric immunophenotyping and differentiation data confirmed the mesenchymal identity of cultivated hDPSCs. 2,4-D treatment caused a hormetic response in the viability and growth rate of hDPSCs. G0/G1 cell cycle arrest, enhanced ROS level, and reduced ALP activity were detected in hDPSCs treated with EC50 dose of 2,4-D. AO/EB staining showed a higher percentage of alive cells in lower concentrations of the herbicide. The increment in 2,4-D dose and the number of early and late apoptotic cells were increased. DAPI staining and caspase 3/7 assay validated the induction of apoptosis. 2,4-D concentrations up to 100 µM did not affect hDPSCs viability and proliferation. The intense cellular oxidative stress and apoptosis were observed at higher concentration.

Effect of L-carnitine and conjugated linoleic acid supplements on haemoglobin levels and haptoglobin genotype in chronic kidney disease.

OBJECTIVE: To investigate the efficacy of L-carnitine (LC) and conjugated linoleic acid (CLA) supplements on haemoglobin levels and inflammatory markers in chronic kidney disease (CKD) patients with different haptoglobin (HP) genotypes. METHODS: This clinical trial study was conducted at Imam Khomeini Hospital, Ardabil, and Labbafinejad Hospital, Tehran, Iran, from March 2014 to March 2015, and comprised male patients with CKD and anaemia. Anthropometric factors were recorded and demographic data was collected using general questionnaires. LC (1 g/day) and CLA (2.4 g/day) supplements were given to the patients for a month. Blood samples were taken to measure haematological and inflammatory markers at the beginning and end of the study. Haptoglobin genotypes were determined using polymerase chain reaction (PCR). SPSS 21 was used for data analysis. RESULTS: Among the 40 patients in the study, HP2-2 genotype was the most prevalent genotype (62.5%). The level of haemoglobin was significantly increased in the patients at the end of the study (p< 0.05). No significant changes were found in the weight, body mass index and serum levels of Interleukin-6, high-sensitivity C-reactive protein, ferritin, total iron-binding capacity and iron (p>0.05 each). CONCLUSIONS: Regular diet supplementation with LC plus CLA can improve haemoglobin levels in CKD patients with anaemia.

The effect of probiotic yoghurt consumption on oxidative stress and inflammatory factors in young females after exhaustive exercise.

OBJECTIVE: To evaluate the effect of probiotic yoghurt consumption on oxidative stress and inflammatory factors in young females after exhaustive exercise. METHODS: TThis study included 27 healthy participants with an age range of 18-25. For two weeks, 450 grams of probiotic yoghurt and 450 grams of ordinary yoghurt were given to the supplement and control groups, respectively. Fasting blood samples were taken at baseline and at the end of study. At the end of the intervention, the participants were given one exhaustive exercise and then fasting blood samples were taken to test for blood antioxidant enzymes, inflammatory markers, and oxidative markers. Data were analyzed using descriptive statistics as well as paired and independent samples t-test. RESULTS: In supplement group, the glutathione peroxidise (GPX) blood levels and serum levels of total antioxidant capacity (TAC) significantly increased at the end of two weeks of intervention (p<0.05). After intense physical activity, the blood levels of superoxide dismutase (SOD), GPX and serum levels of TAC significantly increased, whereas the serum level of tumour necrosis factor alpha (TNF-?), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and malondialdehyde (MDA) significantly decreased in the supplement group compared to the control group (p<0.05). Besides, there were no significant changes in other biochemical factors. CONCLUSIONS: Regular probiotic yoghurt consumption significantly modulated MMP2, MMP9 and some inflammatory factors, and thus guarded against exhaustive exercise-inducing oxidative injury in young healthy females.

Molecular mechanism and cytotoxicity of allicin and all-trans retinoic acid against CD44+ versus CD117+ melanoma cells.

BACKGROUND: All-trans retinoic acid (ATRA) is a differentiating agent that inhibits cancer cell growth during the cell cycle. However, despite its potent antitumor properties, some melanoma cells are resistant to ATRA therapy. PURPOSE: Here, we hypothesized that allicin can sensitize malignant melanoma cells to ATRA treatment. To clarify this mechanism, we determined the sensitivity to ATRA, allicin and allicin/ATRA in CD44+ and CD117+ melanoma cell subpopulations. METHODS: The CD44+and CD117+cells were sorted from A375 melanoma cell line using the magnetic-activated cell sorting (MACS). The potential anticancer effects of ATRA, allicin and allicin/ATRA were examined using cell proliferation MTT assay. In addition, flow cytometry was used to detect cell cycle arrest. The efficacy of the treatments in controlling cancer cell proliferation was assessed by quantitative realtime polymerase chain reaction (RT-PCR). RESULTS: Here, we demonstrated that CD44+ melanoma cells were more resistant to allicin and ATRA than CD117+ cells. Importantly, we observed that allicin sensitized melanoma cell to ATRA-induced cell death. The combination treatment with allicin and ATRA significantly reduced the IC50 value obtained for ATRA alone in CD44+ melanoma cells. In CD44+ cells, the IC50 value of ATRA was 37.43 ±â€¯0.54, while the IC50 value of allicin/ATRA treatment was 17.53 ±â€¯0.2 µM. Allicin treatment resulted in significant increases in the percentage of cells at the G2/M and G0/G1 phases in the CD44+ and CD117+ cells, respectively. The combination treatment caused the inhibition of CD44+ and CD117+ melanoma cells at the S phases compared to ATRA alone. Allicin, ATRA, and allicin/ATRA increased the expression of cyclin D1 mRNA in both CD44+ and CD117+ cells. Allicin combination with ATRA increased the mRNA level of RARß in CD117+ cells. Furthermore, allicin alone caused a remarkable reduction of MMP-9 mRNA expression in both CD44+ and CD117+ cells. In contrast, ATRA and the combination treatment significantly increased MMP-9 gene expression in CD44+ cells. CONCLUSION: Overall, our results indicate that allicin reinforces the ATRA-mediated inhibitory effects on CD44+ and CD117+ melanoma cells and may provide a new approach for the treatment of malignant melanoma.

Mesenchymal Stromal Stem Cell-Derived Microvesicles Enhance Tumor Lysate Pulsed Dendritic Cell Stimulated Autologous T lymphocyte Cytotoxicity

Background: Immunotherapy is one promising therapeutic strategy against glioma, an aggressive form of brain cancer. Previous studies have demonstrated that multiple tumor antigens exist and can be used to induce tumor specific T cell responses. Furthermore, recently it was shown that TLR4-primed mesenchymal stem cells (MSCs), also known as MSC1, mostly elaborate pro-inflammatory mediators. Compared to MSCs, MSC-derived microvesicles (MVs) have advantageous properties that present them as stable, long lasting effectors with no risk of immune rejection. Therefore, peripheral blood monocyte derived dendritic cells (MoDCs) have been used to load tumor antigens and stimulate T cell mediated responses in the presence of MSC1-derived MVs in vitro. Methods: The B92 tumor cell line was heated to 43°C for 90 min prior to preparation of tumor cell lysates. MVs were purified by differential ultracentrifugation after isolation, stimulation of proliferation and treatment of MSCs. Autologous T cells isolated from non-adherent cells were harvested during the procedure to generate MoDCs and then incubated with heat stressed tumor cell lysate pulsed DCs in the presence of MSC1-derived MVs. T cells were then co-cultured with tumor cells in 96-well plates at a final volume of 200 µl CM at an effector: target ratio of 100:1 to determine their specific cytotoxic activity. Results: Flow cytometric analysis, T cell mediated cytotoxicity showed that heat stressed tumor antigen pulsed MoDCs and MSC1-derived MVs primed T cells elicited non-significantly enhanced cytotoxic activity toward B92 tumor cells (P≥0.05). Conclusion: These findings may offer new insights into tumor antigen presenting technology involving dendritic cells and MSC1-derived MVs. Further exploration of the potential of such nanoscale particles in immunotherapy and in novel cancer vaccine settings appears warranted.

Ral signaling pathway in health and cancer.

The Ral (Ras-Like) signaling pathway plays an important role in the biology of cells. A plethora of effects is regulated by this signaling pathway and its prooncogenic effectors. Our team has demonstrated the overactivation of the RalA signaling pathway in a number of human malignancies including cancers of the liver, ovary, lung, brain, and malignant peripheral nerve sheath tumors. Additionally, we have shown that the activation of RalA in cancer stem cells is higher in comparison with differentiated cancer cells. In this article, we review the role of Ral signaling in health and disease with a focus on the role of this multifunctional protein in the generation of therapies for cancer. An improved understanding of this pathway can lead to development of a novel class of anticancer therapies that functions on the basis of intervention with RalA or its downstream effectors.

Anti-inflammatory effects of conjugated linoleic acid on young athletic males.

OBJECTIVE: To explore the efficacy of conjugated linoleic acid supplementation on some inflammatory factors in young healthy males during exhaustive exercise. METHODS: The randomised double-blind controlled study was conducted at Ardabil University of Medical Sciences, Iran, from December 2012 to March2013, and comprised healthy male athletes 18-24 years of age. The subjects were randomly distributed into control and intervention groups. About 5.6 g/day conjugated linoleic acid supplement and oral paraffin (placebo) were given to intervention and control groups respectively daily for two weeks. Fasting blood samples were taken at baseline and at the end of the two weeks of intervention. The subjects underwent exhaustive exercise and then fasting blood samples were taken. Serum levels of tumour necrosis factor alpha, interleukin-6, high-sensitivity C-reactive protein, matrix metalloproteinases-2 and 9 were measured. RESULTS: There were 23 subjects in the study, with 13(56.5%) in the supplemented group and 10(43.4%) in the control group. Serum levels of matrix metalloproteinases-2 and tumour necrosis factor alpha were significantly decreased in the supplemented group (p<0.05). After exhaustive exercise, serum levels of matrix metalloproteinases-2, high-sensitivity C-reactive protein and tumour necrosis factor alpha significantly decreased in the supplemented group compared to the control group(p<0.05). CONCLUSIONS: Two-week administration of conjugated linoleic acid reduced the inflammatory factors following exhaustive exercise in young healthy males.

Low-dose all-trans retinoic acid enhances cytotoxicity of cisplatin and 5-fluorouracil on CD44(+) cancer stem cells.

Cis-diamminedichloridoplatinum(II)(CDDP)-based combination chemotherapy is frequently used in gastrointestinal cancer. The synergistic mechanism of all-trans retinoic acid (ATRA), cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear. Despite their potent antitumor properties, resistance to CDDP and 5-FU develops frequently in tumors. To clarify this mechanism, we determined the sensitivity to each drug and their combination in two gastrointestinal cancer stem cells (CSCs) subpopulation. Here, we report the identification and separation of CD44(+) cells from human gastric carcinoma (AGS) and human esophageal squamous cell carcinoma (KYSE-30) cancer cell lines by magnetic activated cell sorting (MACS). We allowed the CD44(±) cells to grow 6 days at a subtoxic concentration of ATRA and then treated with different concentration of CDDP and 5-FU for 24h. The cytotoxicity was examined by cell proliferation MTT assay. Additionally, AO/EB staining was used for detection of apoptotic cells. In order to determine whether the growth inhibition was also associated with changes in cell cycle distribution, cell cycle analysis was performed using flow cytometry. Low concentration of ATRA (1µM, 6days) followed by 5-FU and CDDP was found to be more effective than either drugs alone, thus resulting in synergistic cytotoxicity in Kyse-30 and AGSCD44(±) cells. Furthermore, there was an indication that the combination of ATRA with 5FU and CDDP caused an increase in cell cycle arrest in G2/M and G0/G1. We conclude that low concentration of ATRA enhances the cytotoxicity of CDDP and 5FU by facilitating apoptosis and cell cycle arrest in gastrointestinal CSCs and provide a rational basis for the design of novel, well-tolerated CDDP- and 5FU-based chemotherapy in human gastrointestinal carcinoma.

Pre-administration of turmeric prevents methotrexate-induced liver toxicity and oxidative stress.

BACKGROUND: Methotrexate (MTX) is an antimetabolite broadly used in treatment of cancer and autoimmune diseases. MTX-induced hepatotoxicity limits its application. We investigated hepatoprotective effects of turmeric in MTX-induced liver toxicity. METHODS: All experiments were performed on male Wistar albino rats that were randomly divided into six groups. Group one received saline orally for 30 days (control group), groups two and three received turmeric extract (100, 200 mg/kg respectively) orally for 30 days, group four received single dose, of MTX IP at day 30, groups five and six received turmeric extract 100 and 200 mg/kg orally respectively for 30 days and single dose of methoterxate IP (20 mg/kg) at day 30. Four days after MTX injection animals were sacrificed and evaluated. Blood ALT and AST (indicators of hepatocyte injury), ALP and bilirubin (markers of biliary function), albumin (reflect liver synthetic function) as well as the plasma TAS concentration (antioxidant defenses) were determined. The cellular antioxidant defense activities were examined in liver tissue samples using SOD, CAT, and GSH-Px for the oxidative stress, and MDA for lipid peroxidation. In addition, liver damage was evaluated histopathologically. RESULTS: MTX significantly induced liver damage (P<0.05) and decreased its antioxidant capacity, while turmeric was hepatoprotective. Liver tissue microscopic evaluation showed that MTX treatment induced severe centrilobular and periportal degeneration, hyperemia of portal vein, increased artery inflammatory cells infiltration and necrosis, while all of histopathological changes were attenuated by turmeric (200 mg/kg). CONCLUSION: Turmeric extract can successfully attenuate MTX-hepatotoxicity. The effect is partly mediated through extract's antinflammatory activity.

Cytotoxic Effects of Newly Synthesized Palladium(II) Complexes of Diethyldithiocarbamate on Gastrointestinal Cancer Cell Lines.

As a part of a drug development program to discover novel therapeutic and more effective palladium (Pd) based anticancer drugs, a series of water-soluble Pd complexes have been synthesized by interaction between [Pd (phen)(H2O)2(NO3)2] and alkylenebisdithiocarbamate(al-bis-dtc) disodium salts. This study was undertaken to examine the possible cytotoxic effect of three novel complexes (0.125-64 µg/mL) on human gastric carcinoma (AGS), esophageal squamous cell carcinoma (Kyse-30), and hepatocellular carcinoma (HepG2) cell lines. The cytotoxicity was examined using cell proliferation and acridine orange/ethidium bromide (AO/EB) assay. In order to examine the effects of new Pd(II) complexes on cell cycle status, we performed cell cycle analysis. The complexes were found to have completely lethal effects on the cell lines, and the half maximal inhibitory concentration (IC50) values obtained for the cell lines were much lower in comparison with cisplatin. We demonstrated that the three new Pd(II) complexes are able to induce G2/M phase arrest in AGS and HepG2; in addition, the Pd(II) complexes caused an S phase arrest in Kyse-30 cell line. Our results indicate that newly synthesized Pd(II) complexes may provide a novel class of chemopreventive compounds for anticancer therapy.

Protective effect of turmeric extract on ethotrexate-induced intestinal damage and oxidative stress.

AIM: The most important side effect of methotrexate (MTX) is mucositis. The purpose of this study was to evaluate the effect of turmeric extract on intestinal damage and oxidative stress in rats receiving methotrexate. METHODS: Experiments were performed on male Wistar albino rats divided into six groups. First group received normal saline orally, the second group received turmeric extract (100 mg·kg(-1)) orally for 30 days, the third group received turmeric extract (200 mg·kg(-1)) orally for 30 days, the fourth group received a single dose of methotrexate (20 mg·kg(-1)) i.p. at day 30, the fifth group received turmeric extract (100 mg·kg(-1)) orally for 30 days and a single dose of methotrexate (20 mg·kg(-1)) i.p. at day 30, and the sixth group received turmeric extract (200 mg·kg(-1)) orally for 30 days and single dose of methotrexate (20 mg·kg(-1)) i.p. at day 30. Four days after methotrexate injection, animals were anesthetized, blood samples were taken to determine total antioxidant status (TAS) and jejunum samples were taken for glutathione peroxidase (GPx), superoxidase dismutase (SOD), catalase (CAT), aldehyde malondialdehyde (MDA), and histopathological assessment. RESULTS: Microscopic evaluation from intestinal tissues of the MTX treated group, showed severe villus shortening and blunting, inflammatory cell infiltration and hemorrhage in lamina propria, along with epithlial cell necrosis. Levels of SOD, GSH-Px and CAT decreased in the MTX received group, but increased significantly (P < 0.05) in the turmeric + MTX groups. MTX increased lipid peroxidation, however, turmeric decreased peroxidation significantly (P < 0.05). CONCLUSION: These results suggest that turmeric extract may protect the small intestine of rats from methotrexate-induced damage. Turmeric effects could result from its antioxidant properties.

Decrease in gastric cancer susceptibility by MTHFR C677T polymorphism in Ardabil Province, Iran.

BACKGROUND/AIMS: Gastric cancer, as the fourth most frequent malignancy worldwide, has the highest rate among cancer-related disorders in Ardabil province, located in North-West Iran. Methylene tetrahydrofolate reductase is one of the cancer susceptibility genes with considerable polymorphisms. Methylene tetrahydrofolate reductase C677T leads to a decrease of about 30% in its product activity and is reported to have an effect on cancer susceptibility. MATERIALS AND METHODS: Methylene tetrahydrofolate reductase C677T genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism on peripheral blood DNA from 76 gastric cancer patients and 91 healthy controls. The statistical significance was calculated by logistic regression analysis. RESULTS: The mean age was 64.2±11.1 and 62.1±9.8 years for cases and controls, respectively. Among tumors, 35.5% were diffuse type and others were intestinal. The frequency of genotypes was 61.8%, 32.9%, and 5.3% among cases and 45.1%, 50.6%, and 4.4% among controls for Ala/Ala, Ala/Val, and Val/Val, respectively. CT heterozygotes had lower susceptibility to gastric cancer (p=0.02). This relationship of significance was detected considering gender and age. CONCLUSIONS: It was found that T allele has a protective association with age in the Ardabil province.

Effects of zinc supplementation on antioxidant status and lipid peroxidation in hemodialysis patients.

OBJECTIVES: This study was designed to determine the effects of zinc supplementation on oxidative stress in hemodialysis (HD) patients through evaluating total antioxidant capacity (TAC), whole blood glutathione peroxidase (GSH) level, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) level. DESIGN AND SETTING: Double-blinded randomized controlled trialfrom October 2006 to December 2007 at Tabriz Imam Khomeini Hospital. SUBJECTS: Sixty-five HD patients were randomly enrolled into 2 groups. INTERVENTION: Patients received placebo in group A and zinc (100 mg/day) in group B for 2 months. After a washout period for 2 months, the groups were crossed over and the study was continued for an additional 2 months. MAIN OUTCOME MEASURES: Serum zinc concentration was measured using atomic absorption spectrophotometry. TAC, GSH level, and SOD activity were determined by commercial enzyme-linked immunosorbent assay kits. MDA level was measured using a thiobarbituric acid method. RESULTS: The levels of serum zinc, TAC, GSH (P < .001 for all), and SOD activity (P < .001 for group A and P = .003 for group B) significantly increased after zinc supplementation whereas the serum level of MDA decreased after the same period (P = .003 for group A and P < .001 for group B). CONCLUSIONS: Zinc supplementation for 2 months improved the serum levels of zinc, antioxidant status, and lipid peroxidation in HD patients.

Cytotoxicity of methylsulfonylmethane on gastrointestinal (AGS, HepG2, and KEYSE-30) cancer cell lines.

PURPOSE: This study was conducted to assay cytotoxic effects of methylsulfonylmethane (MSM) on gastrointestinal cancer cell lines. METHODS: Human gastric carcinoma (AGS), human hepatocellular carcinoma (HepG2), and human esophageal squamous cell carcinoma (KYSE-30) cancer cell lines were treated by MSM and incubated for 24, 48, and 72 h. Cytotoxicity was examined through MTT, neutral red uptake, and protein measurement assays. Ethidium bromide/acridine orange (EB/AO) staining was used for apoptotic cell detection. A diamidino-2-phenylindole staining method was used to analysis cell cycle by flow cytometry. RESULTS: IC(50) of MSM on AGS, HepG2, and KYSE-30 cell lines were 28.04, 21.87 and 27.98 mg/ml after 72 h, respectively. The EB/AO staining showed an increase in apoptotic cells. Cell cycle analysis showed a significant increase in cell density at G2/M phase. CONCLUSION: MSM had cytotoxic effect on cancer cell lines but HepG2 cell line was more susceptible. This study suggests that MSM may induce cytotoxic effect on gastrointestinal cancer cell lines by apoptosis and cell cycle arrest.