The influence of serum selenium in differential epigenetic and transcriptional regulation of CPT1B gene in women with obesity.

INTRODUCTION: The increasing prevalence of obesity has become a major health problem worldwide. The causes of obesity are multifactorial and could be influenced by dietary patterns and genetic factors. Obesity has been associated with a decrease in micronutrient intake and consequently decreased blood concentrations. Selenium is an essential micronutrient for human health, and its metabolism could be affected by obesity, especially severe obesity. This study aimed to identify differential methylation genes associated with serum selenium concentration in women with and without obesity. METHODOLOGY: Thirty-four patients were enrolled in the study and divided into two groups: Obese (Ob) n = 20 and Non-Obese (NOb) n = 14, according to the Body Mass Index (BMI). Anthropometry, body composition, serum selenium, selenium intake, and biochemical parameters were evaluated. DNA extraction and bisulfite conversion were performed to hybridize the samples on the 450k Methylation Chip Infinium Beadchip (Illumina). Bioinformatics analysis was performed using the R program and the Champ package. The differentially methylated regions (DMRs) were identified using the Bumphunter method. In addition, logarithmic conversion was performed for the analysis of serum selenium and methylation. RESULTS: In the Ob group, the body weight, BMI, fat mass, and free fat mass were higher than in the NOb group, as expected. Interestingly, the serum selenium was lower in the Ob than in the NOb group without differences in selenium intake. One DMR corresponding to the CPT1B gene, involved in lipid oxidation, was related to selenium levels. This region was hypermethylated in the Ob group, indicating that the intersection between selenium deficiency and hypermethylation could influence the expression of the CPT1B gene. The transcriptional analysis confirmed the lower expression of the CPT1B gene in the Ob group. CONCLUSION: Studies connecting epigenetics to environmental factors could offer insights into the mechanisms involving the expression of genes related to obesity and its comorbidities. Here we demonstrated that the mineral selenium might play an essential role in lipid oxidation via epigenetic and transcriptional regulation of the CPT1B gene in obesity.

Hydroxymethylnitrofurazone lymphatic uptake with nanostructured lipid carrier after oral administration in rats.

Background: Leishmaniasis, caused by the protozoan Leishmania sp., infects phagocyte cells present in lymphatic organs. This study demonstrates the influence of nanostructured lipid carrier-loaded hydroxymethylnitrofurazone (NLC-NFOH) on lymphatic uptake using a chylomicron-blocking flow model in rats. Method: Lymphatic uptake of NFOH was assessed 1 h after oral administration of dimethyl sulfoxide with NFOH or NLC-NFOH with and without cycloheximide pretreatment. Result: Dimethyl sulfoxide with NFOH and NLC-NFOH showed NFOH serum concentrations of 0.0316 and 0.0291 µg/ml, respectively. After chylomicron blocking, NFOH was not detected. Conclusion: Despite log P below 5, NFOH was successfully taken up by the lymphatic system. Long-chain fatty acids and particle size might be main factors in these findings. NLC-NFOH is a promising and convenient platform for treating leishmaniasis via oral administration.

Household Salt Storage and Seasoning Consumption Are Predictors of Insufficient Iodine Status Among Pregnant Women in Southeastern Brazil.

Iodine deficiency in pregnancy may lead to adverse maternal and fetal outcomes, including impaired child development. Sociodemographic factors and different dietary habits may be related to iodine status in pregnant women. The aim of this study was to evaluate the iodine status and its predictors among pregnant women in a city of Southeastern Brazil. This cross-sectional study was conducted with 266 pregnant women receiving prenatal care in 8 primary health care units. Sociodemographic, obstetric and health, habits of acquisition, storage and consumption of iodized salt, and dietary iodine intake data were collected through a questionnaire. The iodine content was evaluated in urinary iodine concentration (UIC), household salt and seasonings, and drinking water samples. Pregnant women were categorized into three groups according to the UIC, determined by iodine coupled plasma-mass spectrometry (ICP-MS): insufficient (< 150 µg/L), adequate (150-249 µg/L), and more than adequate iodine nutrition (≥ 250 µg/L). The median (p25-p75) UIC was 180.2 µg/L (112.8-262.7). It was found 38% and 27.8% of insufficient and more than adequate iodine nutrition, respectively. Number of gestations, KI content of supplement, alcohol consumption, salt storage, and frequency of using industrialized seasoning were associated to iodine status. Alcohol consumption (OR = 6.59; 95%CI 1.24-34.87), pack the salt in opened container (OR = 0.22; 95%CI 0.08-0.57), and use industrialized seasoning weekly (OR = 3.68; 95% CI 1.12-12.11) were predictors of iodine insufficiency. The pregnant women evaluated have adequate iodine nutrition. Household salt storage and seasoning consumption were risk factors for insufficient iodine status.

Methylmercury exposure-induced reproductive effects are mediated by dopamine in Caenorhabditis elegans.

Methylmercury (MeHg) is a neurotoxicant that exists in the natural environment, which level can be greatly increased because of human activity. MeHg exposures have the risk of being detrimental to the development of the nervous system. Studies on MeHg toxicity have largely focused on the mechanisms of its neurotoxicity following developmental exposures. Additionally, reproductive toxicity of developmental MeHg exposures has been noted in rodent models. The model organism Caenorhabditis elegans (C. elegans) is a self-fertilizing animal which has a short lifespan around 20 days. Most C. elegans are hermaphrodites that can generate both sperm and oocytes. To investigate the effects of developmental MeHg exposures on the reproduction in C. elegans, larvae stage 1 worms were exposed to MeHg (0, 0.01 or 0.05 µM) for 24 h. The laid eggs and oocytes were compared during each day at adult stages for 6 days. We showed that MeHg exposure significantly induced an increased number of eggs in day 1 adults without an effect on the timing of egg laying or the total number of eggs or oocytes over the 6-day period. The expression of dat-1 and cat-2 and dopamine levels were increased in worms exposed to MeHg. Supplementation with 100 µM dopamine recapitulated the effect of MeHg on the number of eggs present in day 1 adults. Furthermore, the effect of MeHg on the number of eggs was abrogated in the cat-2 mutant worms CB1112. The number of oocytes in the 6-day adult stages was decreased by MeHg in the dat-1 mutant RM2702. MeHg exposures did not change the mating rate or the number of offspring from mating. Combined, these novel findings show that developmental exposure to low levels of MeHg has limited effects on the reproduction in C. elegans. Furthermore, our data support a modulatory role of dopamine in MeHg-induced effects on reproduction in this model system.

Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil.

OBJECTIVES: This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. METHODS: A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. RESULTS: The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. CONCLUSIONS: The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.

Urinary iodine and sodium concentration and thyroid status in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

OBJECTIVES: To evaluate urinary iodine concentration (UIC) in civil servants aged 35-74 years of the Brazilian Study of Adults Health (ELSA-Brasil) to analyze its relationship with sociodemographic, clinical risk factors, lifestyle, urinary Na and thyroid status. DESIGN: Cross-sectional study in six Brazilian cities. METHODS: This analysis included 792 participants with information about urinary iodine concentration (UIC). Thyroid status was defined by serum levels of TSH/FT4 and the current use of antithyroid drugs for treatment of overt hyperthyroidism or levothyroxine to treat overt hypothyroidism. The determination of UIC was carried out with an inductively coupled plasma mass spectrometer (ICP-MS) and was expressed as median with Interquartile Range (IQR). RESULTS: In 792 participants, thereof 52% women, mean age was 51.9 (9.0) years. The median UIC was 219 (IQR, 166-291) for all persons studied, thereof 211 (IQR, 157-276) for women and 231 (IQR, 178-304) for men. According to the WHO classification, for all persons studied, 60% had more than adequate iodine-supply (UIC ≥200 µg/L), 37% were adequately supplied (UIC 100-199 µg/L) and <3% had a deficient iodine status (<100 µg/L). In the 35-44-year age strata, which includes women of childbearing age, 23.2% of women presented less than 150 µg/L of UIC. No differences in UIC were detected according to thyroid status. (P = 0.39) The correlation between Ur-Na and UIC showed a Spearman coefficient of 0.52 (P < 0.0001) and it was also found an association of Ur-Na with UIC: Beta of 1.76 (95% Confidence Interval (95% CI): 1.01 to 2.51. The urinary Na concentration showed a synergy with the UIC, that means medians of 57, 72, 107 and 141 mmol Na/L urine (P < 0.001) in the groups with the four UIC classes according to the WHO grading mentioned above. The very low Na content in the persons exhibiting <100 µg/L UIC seems to reflect also a higher urine volume due to the frequent use of diuretics. The strong relationship between the urinary Na concentration and the UIC points to a dependence of the UIC on the individual consumption of iodized salt, which should be more considered in future studies. The strong relationship between the urinary Na concentration and the UIC points to a dependence of the UIC on the individual consumption of iodized salt, which should be more considered in future studies. CONCLUSIONS: Euthyroid persons were dominating by more than four fifths and no significant association was found between UIC and thyroid status. Although most of the persons studied present more than adequate iodine intake it was observed that nearly a quarter of women in childbearing age are iodine deficient.

A fast and direct determination of bisphenol S in thermal paper samples using paper spray ionization mass spectrometry.

Concerns about human health regarding the large use of bisphenol A in thermal papers have led to its replacement by bisphenol S. Analyses of bisphenols require several sample pretreatment steps, which are laborious, expensive, and time-consuming. A paper spray ionization mass spectrometry (PSI-MS) was developed to detect and quantify bisphenol S in three different brands of thermal papers commercially available. Parameters such as paper size, and paper position relative to the mass spectrometer inlet were evaluated. The analyses were performed in selected ion monitoring mode on a linear ion trap mass spectrometer. The developed method presented absolute recovery values ranging from 92.2 to 109.04%, accuracy values from -1.2 to 9.0%, and inter assay precision from 1.8 to 5.6% and enabled LOD as low as 5 ng g-1. The concentration of bisphenol S in all of the three brands of BPA-free thermal papers evaluated ranged from 1.36 to 6.77 µg g-1, and the concentrarion of BPA ranged from 6.56 to 16.4 µg g-1 in all samples of thermal paper evaluated. The PSI-MS method described here was comparable to the conventional ones, such as liquid chromatography coupled with mass spectrometry and gas chromatography coupled with mass spectrometry described in the literature. The present study proved to be practical, fast, and efficient for the direct determination of bisphenol S in thermal papers. Furthermore, the methodology here described showed to be a promising alternative to replace the classical methods for determination of bisphenol S, due to its simplicity, and no needing of any sample pretreatment.

Low urinary selenium levels are associated with iodine deficiency in Brazilian schoolchildren and adolescents.

BACKGROUND: Selenium (Se) and iodine (Io) are important micronutrients for the proper functioning of the thyroid gland, as they are crucial for the synthesis and activation of the thyroid hormones (TH) triiodothyronine (T3) and thyroxine (T4). OBJECTIVE: To evaluate the Se and Io nutritional status among schoolchildren. METHODOLOGY: Cross-sectional, descriptive and analytical study conducted in 982 schoolchildren aged 6-14 years from public schools in the state of Bahia, Brazil. Sociodemographic and anthropometric variables, as well as urinary Se (USC) and Io concentrations (UIC) using the inductively coupled plasma mass spectrometry (ICP-MS) method and thyroid-stimulating hormone (TSH) from filter paper blood collection, were evaluated. RESULTS: The median USC and UIC were 38.7 and 210.0 (IQR: 26.8-52.9 and 129.3-334.1 µg/L, respectively). The prevalence of iodine deficiency and excessive UIC were observed in 17.1% and 30.9% of schoolchildren, respectively. Concomitant low USC and IoD was found in 3.9% of schoolchildren. There was a positive correlation between USC and UIC (r = 0.60; p = 0.00). The median TSH was 0.95 (IQR: 0.69-1.30 µUI/L). CONCLUSIONS: This study demonstrates that USC is a good biomarker for assessing Se status, meantime more studies are needed to establish cutoff USC in child population. Despite adequate median intake, a subgroup of schoolchildren had IoD and low USC. The correlation between UIC and USC point at the importance of two micronutrients, raising the question whether measuring Se should be included in monitoring programs that address the prevention of nutritional disturbances.

Association of Salt Iodization and Urine Iodine Concentration in Schoolchildren from Public Schools in Northeast of Brazil.

Iodine deficiency (ID) is recognized as a leading risk factor for child development. Universal salt iodization (USI) is an effective and well-established intervention strategy for the prevention of iodine deficiency disorders (IDD). To evaluate the levels of iodine in household salt samples and the urinary iodine concentration (UIC) in schoolchildren aged 6 to 14 years in public schools in Bahia, Brazil. A cross-sectional study was conducted with 1231 students (6 to 14 years old) from 17 public schools in Bahia. The iodine concentration was evaluated in salt and UIC samples. The adapted Sandell-Kolthoff reaction was used to determine urinary iodine levels. A spectrophotometer (UV-Vis) was used to examine the reduction of ceric ammonium sulfate. A standard iodine solution using a potassium iodate was used to extrapolate the iodine concentrations. The total of 665 salt samples had a median iodine concentration of 24 mg/kg (25th-75th percentile 17.0 to 28.5 mg/kg). The largest proportion (79.6%) of salt samples had iodine concentration in the recommended range, 17.6% of the samples presented iodine at a salt concentration below the established level (<15 mg/kg) and a small proportion was above it (2.8%). The general mean urinary iodine concentration (MUIC) was 217.53 ± 28.30 µg/L and median was 205.50 µg/L. The students evaluated and the salt samples analyzed showed satisfactory results, as recommended by Brazilian legislation and nutritional recommendations of the World Health Organization (WHO).

Occurrence and abundance of clinically relevant antimicrobial resistance genes in environmental samples after the Brumadinho dam disaster, Brazil.

On January 25th 2019, the structure damming a pond containing ore mining wastes and iron burst at Brumadinho City, Brazil. About 11.7 million m3 of a tailings-mud mixture was released from the dam, causing destruction along 300 km of the Paraopeba River toward the São Francisco River. The environments with a high content of metals may provide a suitable environment for horizontal gene transfer, including antimicrobial resistance genes (ARGs). Therefore, this study aimed to detect and quantify clinically relevant ARGs in environmental samples after the Brumadinho dam disaster. Soil, sediment, and water samples were collected within 300 km of the Brumadinho dam disaster at unaffected and affected sites. Physical-chemical parameters of water samples were measured. Total DNA was extracted and 65 clinically relevant ARGs were researched by PCR. The most prevalent ARGs were selected for real-time quantitative PCR analysis. The average of the physical-chemical parameters was higher in the affected sites when compared to the unaffected sites, especially turbidity, concentration of Fe and Al. A total of 387 amplicons from 29 ARGs were detected, which confer resistance to ß-lactams, quinolones, aminoglycosides, tetracyclines, sulphonamides, phenicols, macrolides, glycopeptides, and polymyxins, including extended-spectrum ß-lactamases-encoding genes, and mcr-7.1. The sul1 gene had higher total concentrations than blaTEM, tetB and qnrB in the environmental samples, and the diversity and abundance of ARGs increased at the sites affected by the Brumadinho dam disaster. Therefore, we point out that the contamination by the Brumadinho dam disaster tailings resulted in an increase in the amount and abundance of ARGs in the environment.

Edible weeds: Are urban environments fit for foraging?

Foraging wild-growing edible plants (WEPs) is a re-emerging practice with increasing popularity worldwide, including in urban areas. However, in cities, this practice raises questions about the safety of foraging these plants for human consumption, due to the potential exposure of plants to higher levels of pollutants. In this study, the concentration of 12 elements (Al, V, Cr, Mn, Co, Ni, Zn, As, Rb, Cd, Ba and Pb) in three different WEPs (Amaranthus spp., Plantago tomentosa and Taraxacum officinale) were determined according to different traffic categories in the municipality of São Paulo. Additionally, plants were sampled within the inner areas of three municipal parks in the same study region. Different gradients of elemental concentrations were obtained according to the traffic categories. Freeways presented higher concentrations of several elements than local roads or parks. For the WEPs collected along freeways and some plants along arterial roads, the concentrations of Pb exceeded safety levels for human consumption. Our data suggest that foraging in large urban centres should be performed preferentially in low-traffic areas.

Baru Almonds Increase the Activity of Glutathione Peroxidase in Overweight and Obese Women: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Obesity-induced inflammation is frequently associated with higher oxidative stress. In vitro and experimental studies have considered baru almonds (Dipteryx alata Vog) as a legume seed with high antioxidant capacity. The aim of this study was to evaluate whether baru almonds are capable of improving the inflammatory and antioxidant status in overweight and obese women. METHODS: In a parallel-arm, randomized placebo-controlled trial, 46 overweight and obese women (age: 40 ± 11 years; body mass index: 33.3 ± 4.3) were randomly assigned to receive advice to follow a normocaloric and isoenergetic diet with placebo (PLA, n = 22) or similar advice plus 20 g baru almonds (BARU, n = 24) for 8 wk. Malondialdehyde (MDA), adiponectin, tumor necrosis factor-α, interleukin-6, interleukin-10, antioxidant enzymes activities (catalase-CAT; glutathione peroxidase-GPx; superoxide dismutase-SOD), and minerals were analyzed in plasma samples. RESULTS: At baseline, groups were similar regarding the body composition, oxidative, and inflammatory parameters. The BARU group increased the activity of GPx (+0.08 U/mg, 95%CI + 0.05 to +0.12 vs. -0.07, 95%CI -0.12 to -0.03, p < 0.01) and plasma copper concentration (p = 0.037) when compared to the PLA group. No differences were observed between groups in CAT and SOD activity or MDA and cytokines concentrations. CONCLUSIONS: Baru almond supplementation increased the GPx activity in overweight and obese women.

Consumption of Brazil nuts with high selenium levels increased inflammation biomarkers in obese women: A randomized controlled trial.

OBJECTIVE: Increased inflammatory response is an important factor in the pathophysiology of obesity. The mineral selenium (Se), of which one of the main food sources is the Brazil nut, has important antioxidant and anti-inflammatory functions through the action of selenoproteins. Thus, the evaluation of the influence of this micronutrient in this context is of great relevance. The aim of this study was to evaluate the effects of Brazil nut intake with high Se concentrations on inflammatory biomarkers and its relation to Se status in obese women. METHODS: A randomized controlled clinical trial was carried out with 55 women recruited at Clinical Hospital in São Paulo, Brazil. Patients were randomly assigned to either the Brazil nut group (BN) or the control group (CO) and followed up for 2 mo. The BN group consumed 1 unit/d of Brazil nuts (∼ 1261 µg/Se); the CO group did not receive any intervention. At baseline and after 2 mo, analysis of biochemical parameters related to Se status, oxidative stress, and inflammatory biomarkers were performed. RESULTS: At baseline, both groups did not present Se deficiency. In the BN group, a significant increase (P < 0.05) in all Se biomarkers and in gene expression of several proinflammatory parameters (interleukin-6, tumor necrosis factor-α, and Toll-like receptors 2 and 4) were observed after the intervention period. No changes were observed for the CO group. CONCLUSION: Although there were no changes in plasma inflammatory biomarkers levels, a significant increase in gene expression may be an indication of a proinflammatory stimulus in obesity, induced by the consumption of Brazil nuts with high Se levels.

Sexual differentiation and reproductive development of female rat offspring after paternal exposure to the anti-tumor pharmaceutical cisplatin.

Cisplatin (CP) is used to treat a number of cancers, including testicular cancer. Studies indicate that CP-treatment can impair spermatogenesis in humans and rodents by germ cell DNA binding, through different modes of action. CP-paternal exposure resulted in adverse effects in F1 male offspring. In this study, F1 female offspring was assessed for reproductive development after CP-paternal exposure. Peri-pubertal male rats, treated with 1mg/Kg/day of CP or vehicle for 3 weeks, were mated with unexposed females. F1 female offspring of CP-treated fathers showed a decrease in fetal ovary germ cells, in estrous cycle length and FSH levels, and an increase in the percentage of antral follicles in adults. Based on our previous results and the findings of the present work we concluded that CP-paternal exposure leads to adverse effects on rat male and female reproductive development, raising concern, in humans, for children born to men exposed to CP.

A longer time of exposure to antiretroviral therapy improves selenium levels.

BACKGROUND & AIMS: Selenium is an essential mineral for immunological function, performing crucial functions at the cellular level. This micronutrient has been determined to be frequently deficient in HIV infected patients, with correlations between reduced immunological function and greater susceptibility to opportunistic infections. Our aim was to evaluate the influence of time of exposure to antiretroviral therapy (ART) on the biochemical profile of selenium in HIV-infected patients. METHODS: We performed a cross-sectional study on 50 HIV-positive men with different quantitations of viral load and CD4+ T cells, who were either receiving or not receiving ART. Dual energy X-ray absorptiometry (DXA) to determine body composition, biochemical analysis of selenium and albumin, anthropometric measurements were performed. The subjects were divided into groups according to the use of ART or not: The Control Group (CG) was 10 treatment-naïve volunteers, Group G < 2 was 20 volunteers on ART for less than 2 years, and Group G > 2 was 20 volunteers on ART for >2 years. RESULTS: The body mass index showed that all subjects were of normal weight. The group with a longer time of exposure to ART (G > 2) had undetectable viremia and a higher CD4+ T cell count: 593.1 ± 234.6 mm(3). Selenium values (µg/L) were 55.9 ± 11.9 for CG, 52.1 ± 10.5 for G < 2, and 66.9 ± 20.8 for G > 2, with a significant difference between groups G < 2 and G > 2 (p < 0.05), and only G > 2 showed normal selenium values. CONCLUSIONS: Most of the men studied showed selenium deficiency, except for the subjects with a longer exposure to antiretroviral treatment. Thus, an adequate selenium concentration is related to better control of virology and of immunologic function.

Quercetin protects human-derived liver cells against mercury-induced DNA-damage and alterations of the redox status.

Aim of this study was to investigate the cytotoxic and genotoxic properties of inorganic and organic mercury compounds, i.e., HgCl(2) and methylmercury (MeHg). In addition, the DNA-protective and antioxidant effects of the flavonoid quercetin (QC) were studied. All experiments were conducted with human-derived liver cells (HepG2), which possess antioxidant and drug-metabolizing enzymes in an inducible form. 8-Hydroxydeoxyguanosine (8-OHdG) and comet formation were monitored as endpoints of DNA damage. The impact of the metal compounds on the redox status was also investigated, since it is assumed that their toxic effects are due to oxidative damage. A number of biochemical parameters related to oxidative stress, namely glutathione, malondialdehyde, protein carbonyl and formation of reactive oxygen species (ROS) were measured after treatment of the cells with the mercury compounds in the presence and absence of quercetin. To elucidate the mechanisms that underlie the effects of QC, three protocols (pre-, simultaneous and post-treatment) were used. Both mercury compounds (range 0.1-5.0µM) caused induction of DNA migration and formation of 8-OHdG. In combination with the flavonoid (range 0.1-5.0µM), DNA-protective effects of QC were observed after pre- and simultaneous treatment but not when the flavonoid was added after treatment with the metal compounds. Exposure to the metal compounds led also to substantial changes of all parameters of the redox status and co-treatment experiments with QC showed that these alterations are reversed by the flavonoid. Taken together, the results of our experiments indicate that these two mercury compounds cause DNA damage and oxidative stress in human-derived liver cells and that the flavonoid reduces these effects. Since the concentrations of the metals and of the flavonoids used in the present work reflect human exposure, our findings can be taken as an indication that QC may protect humans against the adverse effects caused by the metal.

Effect of JNK inhibition on cisplatin-induced renal damage.

BACKGROUND: Cisplatin therapy is effective against many tumours, however, the nephrotoxicity of this drug is a dose-limiting factor. Apoptosis and necrosis of tubular cells and inflammatory events contribute to the cisplatin-induced nephrotoxicity. Cisplatin promotes increased production of reactive oxygen species, which can activate c-jun N-terminal kinase (JNK) that is a mediator of apoptosis and can lead to increased expression of proinflammatory mediators that could intensify the cytotoxic effects of cisplatin. In this study, we evaluated the effect that SP600125, a selective inhibitor of phosphorylated JNK (p-JNK), has on the renal damage caused by cisplatin use. METHODS: A total of 33 male Wistar rats received SP600125 (15 mg/kg/day, s.c., diluted in polyethylene glycol) for 4 days. At 24 h after the first dose, those 33 rats, plus an additional 30, were injected with cisplatin (5 mg/kg, i.p.). In addition, 18 control rats were injected with saline, and 12 rats with polyethylene glycol. At 2 and 5 days after saline or cisplatin injection, blood and urine samples were collected for measurement of creatinine, sodium and potassium, and the kidneys removed for histological, immunohistochemical and Western blot studies. RESULTS: Cisplatin-treated rats presented higher plasma creatinine, as well as greater immunostaining for ED1 (macrophages/monocytes), p-JNK, apoptotic cells, and tubular cell necrosis in the renal cortices and outer medullae. The increase of p-JNK expression was also confirmed by Western blot analysis. All of these alterations were attenuated by treatment with SP600125. CONCLUSION: The protective effect of SP600125 on cisplatin-induced renal damage seems to be related to the reduction in the apoptotic cell death and to the restriction of renal inflammation.