Search

Heart failure (HF) is one of the major cardiovascular causes of death worldwide. In this study, we explored the effects of folic acid (FA) on cardiometabolic, oxidative stress biomarker changes, and the activity of proliferation marker Ki67 in monocrotaline-induced HF. The research was conducted during a 4 week period using five experimental groups (eight animals per group): blank solution exposed controls (C1:1 mL/kg physiological saline, 1 day; C2:1 mL/kg physiological saline, 28 days), monocrotaline (MCT) induced HF (50 mg/kg MCT), FA (5 mg*[kg.sup.-1]*[day.sup.-1] FA), and MCT+FA (50 mg/kg MCT, 5 mg*[kg.sup.-1]*[day.sup.-1] FA). Superoxide dismutase and glutathione peroxidase activities together with total glutathione and parameters of oxidative damage of proteins were determined in cardiac tissue as well as cardiometabolic parameters in plasma or serum. The total glutathionylation was determined by Western blot and proliferation marker Ki67 was assessed by immunohistochemistry. The right ventricular (RV) wall hypertrophy and Ki67 positivity, accompanied by a significant increase of troponin T, has been shown in MCT-induced HF. The antioxidant effect of FA was reflected through superoxide dismutase activity, reduced Ki67 positivity in the RV wall, and a slightly decreased total glutathionylation level. Key words: heart failure, monocrotaline, oxidative stress, folic acid, Ki67, rat. L'insuffisance cardiaque (IC) est l'une des principales causes cardiovasculaires de deces a l'echelle mondiale. Cette etude portait sur les effets de l'acide folique (AF) sur les variations de marqueurs cardiometaboliques et du stress oxydatif, ainsi que sur l'activite du marqueur de proliferation Ki67 dans l'IC engendree par la monocrotaline (MCT). Nous avons mene l'etude pendant 4 semaines sur cinq groupes experimentaux de huit animaux chacun : temoins exposes a une solution a blanc (T1 : solution saline physiologique a 1 mL/kg sur 1 jour; T2 : salin physiologique a 1 mL/kg sur 28 jours), IC engendree par la MCT (a 50 mg/kg), AF (a 5 mg*[kg.sup.-1]*[jour.sup.-1]) et MCT+AF (a 50 mg/kg et a 5 mg*[kg.sup.-1]*[jour.sup.-1], respectivement). Nous avons mesure l'activite de la superoxyde dismutase et de la glutathion peroxydase de pair avec les taux de glutathion total et des parametres des dommages oxydatifs aux proteines dans le tissu cardiaque, ainsi que certains parametres cardiometaboliques dans le plasma ou le serum. Nous avons mesure la glutathionylation totale a l'aide de l'immunobuvardage de Western, et evalue les taux du marqueur de proliferation Ki67 a l'aide de l'immunohistochimie. Nous avons montre une hypertrophie de la paroi du ventricule droit (VD) et la presence du marqueur Ki67 (positivite), avec une augmentation notable des taux de troponine T dans l'IC engendree par la MCT. L'effet antioxydant de l'AF se manifestait par l'activite de la superoxyde dismutase, une diminution de la positivite au marqueur Ki67 dans la paroi du VD, ainsi que par une legere diminution du taux de glutathionylation totale. [Traduit par la Redaction] Mots-cles: insuffisance cardiaque, monocrotaline, stress oxydatif, acide folique, Ki67, rat., Introduction Heart failure (HF), as a chronic heart disease, is one of the leading causes of mortality worldwide. The metabolic requirements of the body are not satisfied because of the [...]

Purpose: To clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) in individual susceptibility to urinary bladder cancer. Methods: Case-control study consisting of 187 patients with histologically confirmed transitional cell carcinoma (TCC) of urinary bladder and 140 age- and gender-matched cancer-free controls was carried out. Genotyping of GSTO1 and GSTO2 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: We found that carriers of mutant GSTO2*G/G genotype were at increased risk of the development of TCC (OR 2.6, 95 % CI 1.2-5.8, p = 0.041), while GSTO1 rs4925 polymorphism was not significantly associated with TCC risk ( p = 0.450). According to smoking status, smokers with GSTO2*G/G genotype had significantly higher risk of TCC of urinary bladder (OR 4.3, 95 % CI 1.6-11.2, p = 0.003) compared to wild-type carriers with no smoking history. We further analyzed the effects of GSTO1/ GSTO2 haplotypes on TCC risk, based on the linkage disequilibrium found for GSTO1 (rs4925) and GSTO2 (rs156697) ( D′ = 0.309, p = 0.001). The study subjects with GSTO1*C/ GSTO2*G ( GSTO1 wild-type/ GSTO2 mutant) haplotype were at the highest risk of the development of transitional cell carcinoma of urinary bladder (OR 2.8, 95 % CI 1.5-5.2, p = 0.002). Conclusions: Our results indicate that GSTO1*C/ GSTO2*G haplotype is associated with increased risk of TCC. The modifying effect of GSTO2*G/G genotype on individual susceptibility to TCC is more pronounced, when associated with smoking. [ABSTRACT FROM AUTHOR]

Omega class glutathione transferases, GSTO1-1 and GSTO2-2, exhibit different activities involved in regulation of inflammation, apoptosis and redox homeostasis. We investigated the the prognostic significance of GSTO1 (rs4925) and GSTO2 (rs156697 and rs2297235) polymorphisms in clear cell renal cell carcinoma (ccRCC) patients. GSTO1-1 and GSTO2-2 expression and phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ /mammalian target of rapamycin (mTOR) and Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathways in non-tumor and tumor ccRCC tissue, as well as possible association of GSTO1-1 with signaling molecules were also assessed. GSTO genotyping was performed by quantitative PCR in 228 ccRCC patients, while expression and immunoprecipitation were analyzed by Western blot in 30 tissue specimens. Shorter survival in male carriers of GSTO1 *C/C wild-type genotype compared to the carriers of at least one variant allele was demonstrated ( p = 0.049). GSTO1 *C/C genotype independently predicted higher risk of overall mortality among male ccRCC patients ( p = 0.037). Increased expression of GSTO1-1 and GSTO2-2 was demonstrated in tumor compared to corresponding non-tumor tissue ( p = 0.002, p = 0.007, respectively), while GSTO1 expression was correlated with interleukin-1β (IL-1β)/pro-interleukin-1β (pro-IL-1β) ratio ( r = 0.260, p = 0.350). Interaction of GSTO1 with downstream effectors of investigated pathways was shown in ccRCC tumor tissue. This study demonstrated significant prognostic role of GSTO1 polymorphism in ccRCC. Up-regulated GSTO1-1 and GSTO2-2 in tumor tissue might contribute to aberrant ccRCC redox homeostasis.