Meta-Analysis of the Association Between the rs228570 Vitamin D Receptor Gene Polymorphism and Arterial Hypertension Risk.

The association between FokI polymorphism in the vitamin D receptor (VDR) gene and susceptibility to arterial hypertension (HT) is controversial. Thus, we evaluated the relation between FokI and HT according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using MEDLINE® (Medical Literature Analysis and Retrieval System Online)/PubMed, Scopus, and Cochrane Library CENTRAL databases. Data from case-control studies, including the number of participants, age, 25-hydroxyvitamin D concentrations, systolic and diastolic blood pressure values, FokI allele, and genotype frequency were extracted by 2 independent authors and OR was calculated with the 95% CI to assess the strength of the association between the FokI variant and odds of HT. In general and subgroup analyses, we used allelic (f compared with F), common (ff compared with FF + Ff), risk (ff + Ff compared with FF), and additive (ff compared with FF) models. Six case-control studies including 3140 cases and 3882 controls were reviewed in the meta-analysis. Global assessment revealed a correlation between FokI and reduced odds of HT in the additive/homozygote model (ff compared with FF; OR: 0.65; 95% CI: 0.45-0.94) and common/recessive model (ff compared with FF + Ff; OR: 0.75; 95% CI: 0.57-0.99). In Asian subjects, there was a significant reduction in the odds of HT in additive (ff compared with FF; OR: 0.84; 95% CI: 0.73-0.98) and risk models (ff + Ff compared with FF; OR: 0.87, 95% CI: 0.78-0.97), in particular, for Indians (South). In Africans, the statistically significant association occurred in the additive and common models. Allele f in the FokI polymorphism of the VDR gene was associated with reduced odds of HT in the general population based on the risk model. Thus, nutritional genomics can help understand the influence of nutrition on metabolic homeostasis pathways and the clinical consequences of hypertension. This study shows the need for healthy, anti-inflammatory, and antioxidant compounds to prevent or treat chronic complications.

Serine protease inhibition and modulatory-antibiotic activity of the proteic extract and fractions from Amburana cearensis.

This study investigated the inhibitory activity of serine protease, as well as antibacterial and antibiotic modifying activities of the crude extract and fractions of A. cearensis seeds. Microdilution assay was used to evaluate the antibacterial activity and the antibiotic resistance-modulating effects of samples against multiresistant bacteria Staphylococcus aureus (SA10) and Escherichia coli (EC06). In the inhibition test for serine protease, all the samples showed inhibition of enzymatic activity. Crude extract and fractions of A. cearensis seeds showed a Minimum Inhibitory Concentration ≥1024 µg/mL for all microorganisms tested. However, the samples acted as resistance modifying agent, presenting synergism when associated with gentamicin, norfloxacin and penicillin. The present study provides data indicating a possible use of the seeds extract of A. cearensis in association with antibiotics in the fight against bacterial infections.

Association of Phytol with Toxic and Cytotoxic Activities in an Antitumoral Perspective: A Meta-Analysis and Systemic Review.

BACKGROUND: Phytol have various pharmacological activities such as antimicrobial, cytotoxic, antitumoral, antimutagenic, anti-atherogenic, antidiabetic, lipid-lowering, antispasmodic, antiepileptic, antinociceptive, antioxidant, anti-inflammatory, anxiolytic, antidepressant and immunoadjuvant. Several studies point to an association of phytol with implications for apoptosis and necrosis at cellular levels in cancer, yet no clear conclusions were drawn. METHOD: To clarify this, we conducted a meta-analysis of non-clinical studies of phytol and its associations with toxicity and cytotoxicity emphasizing the mechanisms of apoptosis and necrosis induction and its importance in tumor therapy. Relevant studies were systematically searched in PubMed and Web of Science. The association between phytol and cyto-/toxicity was assessed by odds ratio (ORs) and 95% confidence intervals (CI). Twentythree studies were finally included in the meta-analysis. A significant association between phytol and toxicity (OR: 1.47; 95% CI = 0.86-2.48) was found among in vivo studies and cytotoxicity (OR: 1.81; 95% CI = 1.12- 2.65, p<0.05) in in vitro and ex vivo studies. In in vitro studies, 24% of them indicate that phytol at high doses induces apoptosis by several mechanisms; while about 40% of ex vivo studies indicate that phytol induces reactive oxygen species generation. But, Phytol does not act as a direct oxidant, unlike its metabolite phytanic acid. The 24% of in vivo studies also highlighted the mechanisms for apoptosis-like including expression of Bcl2 protein or mutations in pro-apoptotic protein Bax. Of them, 8% studies show necrosis and hepatotoxicity. However, in 24% of the articles, the mechanisms of toxicity and cytotoxicity are still not well elucidated. CONCLUSION: This study confirms that the association between phytol and cyto-/toxicity depends on the dose/concentration used in the given experimental conditions. Thus, there are still great prospects for new research aimed at the use of phytol and its metabolite as anticancer agents.

Assessment of chemotherapy on various biochemical markers in breast cancer patients.

Chemotherapy is a standard treatment method for the patients with locally advanced breast cancer. Lately, cyclophosphamide (CYP) and doxorubicin (DOX) are used as the major chemotherapeutic agents especially for the treatment of breast cancer. Till date, no serum biomarker has been able to provide an early diagnosis of breast cancer. This study aimed to assess inflammatory, cardiac, renal and hematological markers in 56 breast cancer patients (BCP) before, during and after termination of chemotherapy with CYP and DOX. Blood samples were collected from the patients at the each treatment stages mentioned above. These samples were assessed for interleukin 6 (IL-6), interleukin 10 (IL-10), lactate dehydrogenase (LDH), creatine kinase (CK), creatinine, hemoglobin (Hb), leukocyte, platelet and Na+ /K+ -ATPase levels either by ELISA or colorimetric methods. The results suggest a significant increase in IL-6 level at all the stages in BCP as compared to control group. On the other hand, IL-10, CK and Na+ /K+ -ATPase levels were found to be significantly declined during all the stages. Moreover, the majority of hematological parameters remained unchanged throughout the treatment period with the exception of creatinine and Hb which showed slight modulation in their level at different stages. Based on the results, we conclude that breast cancer and co-treatment with CYP and DOX, interfere arious biological markers, thereby, showing the physiological imbalance.

The influence of heavy metals on toxicogenetic damage in a Brazilian tropical river.

Anthropogenic activities in tropical rivers favor the eutrophication process, which causes increased concentration of heavy metals. The presence and bioaccumulation of metals are directly related to the presence of genotoxic damage in aquatic organisms. Thus, we evaluated the presence of heavy metals (Fe, Zn, Cr, Cu and Al) and performed toxicogenetic tests in surface (S) and bottom (B) of water samples of the Poti river (Piaui/Brazil). Cytotoxicity and genotoxicity tests were performed in Allium cepa, and micronucleus (MN) and comet assay were performed in Oreochromis niloticus. The chemical analysis showed concentrations above the limit for Cu, Cr, Fe and Al according to Brazilian laws, characterizing anthropogenic disturbance in this aquatic environment. Toxicogenetic analysis presented significant cytotoxic, mutagenic and genotoxic effects in different exposure times and water layers (S and B), especially alterations in mitotic spindle defects, MN formations, nuclear bud and DNA strand breaks. Correlations between Fe and cytotoxicity, and Al and mutagenicity were statistically significant and point out to the participation of heavy metals in genotoxic damage. Therefore, Poti river water samples presented toxicogenetic effects on all bioindicators analyzed, which are most likely related to heavy metals pollution.

Evaluation of Antioxidant Activity of Phytol Using Non- and Pre-Clinical Models.

BACKGROUND: Phytol (3,7,11,15-tetramethylhexadec-2-en-1-ol; PHY), the alcoholic diterpenoid is particularly interesting due to its diverse activities found in literature. This study evaluated in vitro and in vivo antioxidant capacity of PHY. METHODS: We conducted DPPH• (2,2-diphenyl-1-picrylhydrazyl) and ABTS•+ (2,2&#039;-azino-bis(3- ethylbenzthiazoline-6-sulphonic acid)) radical scavenging tests as in vitro, while Saccharomyces cerevisiae test as in vivo. For in vitro tests, trolox and for in vivo test hydrogen peroxide (H2O2) were taken as standard and stressor, respectively. Additionally, we measured the superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), lipid peroxidation (LP) and nitrite (NO2 -) contents in mouse hippocampus taking 0.05% Tween 80 dissolved in 0.9% saline (0.25 ml) and ascorbic acid (250 mg/kg; AA) as vehicle and standard, respectively. PHY was administered at doses 25, 50 and 75 mg/kg. In the latter case, all the treatments were administered via intraperitoneal (i.p.) route. RESULTS: PHY at 7.2 µg/ml exhibited 59.89 ± 0.73% and 62.79 ± 1.99% scavenging capacity of DPPH• and ABTS•+, respectively. In S. cerevisiae strains, PHY showed prominent protective effects. Moreover, in Swiss mouse hippocampus; PHY reduced the LP and NO2 - contents, while increased in GSH, SOD and CAT activities. CONCLUSION: PHY exerted antioxidant potential in our current non- and preclinical test systems and can be a good candidate for the development of treatments of oxidative stress mediated diseases.

Genotoxic and Mutagenic Activity of PT-31.

Toxicity assessment is an important tool in drug discovery and development. PT-31 (3-(2-chloro-6-fluorobenzyl)-imidazolidine-2,4-dione) is an imidazolidine- 2,4-dione analogue of clonidine that displays a dose-dependent analgesic profile and synergism with morphine. This study investigated genotoxic and mutagenic effects of PT-31 in Swiss mice. For this, ten mice (M1:F1) per group were treated with PT-31 intraperitoneally (i.p.) at 0.5, 1.0 and 5.0 mg/kg. The dimethyl sulfoxide (0.5%) and 50 mg/kg cyclophosphamide (i.p.) were taken as negative (NC) and positive controls, respectively. The bone marrow cells were collected after 24 h, while peripheral blood after 30 min, 12 h and 24 h of the treatment for the comet assay. Micronucleus (MN) test was performed only on bone marrow cells collected after 24 h of i.p. treated animals. A hundred cells were considered for the comet assay and quantification of the index of damage and frequency of damage. Lack of genotoxicity with 0.5 mg/kg of PT-31 and DNA repair ability with 0.5 and 1.0 mg/kg doses at 12 h and 24 h in comparison to NC group was observed (P<0.05). There was an increase in MN formation by PT-31 1.0 and 5.0 mg/kg treated female and male mice, respectively. PT-31 induced genotoxic and mutagenic effects only in higher doses.