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1. Introduction Suberoylanilide hydroxamic acid (SAHA) or vorinostat is one of the histone deacetylase inhibitors introduced to clinical trials as an anti-cancer drug and confirmed by the U.S. Food and [...], The comorhidity of depression and high risk of cardiovascular diseases (CVD) have been reported as major health problems. Our previous study confirmed that fluoxetine (FLX) therapy had a significant influence on brain function hut not on the heart in depression. In the present study, suheroyanilide hydroxamic acid (SAHA) was proposed as another therapeutic candidate for treatment of depression comorhid CVD in maternal separation model, following behavioral analyses and gene expression level in the heart. Our data demonstrated that SAHA significantly attenuates the NOX-4 gene expression level in treated mice with SAHA and FLX without significant change in NOX-2 expression level. SAHA decreased the gene expression level of peroxisome proliferator-activated receptor-gamma coactivator (PGC-1[alpha]) and nuclear respiratory factors (Nrf2) in heart tissues of maternally separated mice. It supposed that non-effectiveness of FLX on mitochondrial hiogenesis and NOX gene expression level in the heart of depressed patient can he related to recurrence of depression. It revealed that SAHA not only reversed the depressivelike hehavior similar to our previous data hut also recovered the heart mitochondrial function via effect on NOX-2, NOX-4, and mitochondrial hiogenesis genes' (PGC-1[alpha], Nrf-2, and peroxisome proliferator-activated receptor-[alpha] (PPAR- [alpha])) expression levels. We suggest performing more studies to confirm SAHA as a therapeutic candidate in depression comorhid CVD. Key words: vorinostat (SAHA), depression, NADPH oxidase, mitochondrial hiogenesis, maternal separation (MS), heart On a rapporte que la comorhidite entre la depression et le risque accru de maladies cardiovasculaires (MCV) constitue un prohleme de sante majeur. Notre etude precedente est venue confirmer que l'administration de fluoxetine (FLX) exerce une influence importante sur le fonctionnement du cerveau, mais pas sur le coeur pendant la depression. Dans la presente etude, nous avons propose que l'acide suheranilohydroxamique (SAHA) puisse constituer un autre candidat therapeutique contre la comorhidite entre la depression et les maladies cardiovasculaires dans un modele de separation maternelle (SM) avec l'ajout d'etudes comportementales et de mesures des taux d'expression genique dans le coeur. Nos donnees ont montre que le SAHA entraine une attenuation marquee des taux d'expression du gene NOX-4 chez des souris auxquelles etaient administres du SAHA et de la FLX sans variation appreciahle des taux d'expression de NOX-2. Le SAHA a entraine une diminution des taux d'expression genique de PGC-1[alpha] et de Nrf2 dans le tissu cardiaque des souris du modele de SM. Il est possihle que le manque d'efficacite de la FLX sur la hiogenese mitochondriale et les taux d'expression genique de NOX dans le coeur des patients deprimes puissent etre lies a la recidive de la depression. Nous revelons qu'en plus d'inverser des comportements s'apparentant a la depression un peu comme dans nos donnees anterieures, le SAHA permettrait au fonctionnement mitochondrial du coeur de se retahlir par l'intermediaire d'un effet sur NOX-2, NOX-4 et des taux d'expression des genes de la hiogenese mitochondriale (PGC-1[alpha], Nrf-2 et PPAR-[alpha]). Nous suggerons d'effectuer d'autres etudes en vue de confirmer que le SAHA puisse constituer un agent therapeutique candidat dans la comorbidite entre la depression et les maladies cardiovasculaires. [Traduit par la Redaction] Mots-cles : vorinostat (SAHA), depression, oxydase de la NADPH, biogenese mitochondriale, separation maternelle, coeur

In the present study, cadmium (Cd) and lead (Pb) were monitored in different juice samples including orange, grape, apple and multi-fruit juices collected from Zanjan, Iran. The collected fruit juice samples were digested by using a microwave digestion system and their metals content was determined under graphite furnace atomic absorption spectrometry (GFAAS). In addition, carcinogenic and non-carcinogenic risk resulting from Cd and Pb entered through fruit juice consumption were evaluated. Cd and Pb were detected in more than 41% and 80% of analysed fruit juices. The highest concentration of Pb and Cd was observed in orange juice (99 and 9.4 µg/l). Furthermore, incidence of Pb and Cd in 58.9% and 4.9% of fruit juices were higher than the established Codex maximum permissible level. The data showed that total hazard quotients (THQ) for Pb and Cd metals in fruit juices were less than 1 in adults and children, meaning that no major non-carcinogenic risk is resulted from consumption of fruit juice samples. In Cd, the highest calculated CR at the 95th percentile for carcinogenic risk was 1.47 × 10−5 (multi-fruits for children) and 1.43 × 10−5 (orange juice for children) as determined by Monte Carlo simulation model. In addition, for the carcinogenic risk of Pb in adults and children, the safest risk value (≤10−6) was indicated. The calculated CR of Cd and Pb in juices for adults and children was lower than the permissible carcinogenic risk value set by USEPA (1 × 10−5). Based on the results, fruit juices are not the major source of Cd and Pb intake by Iranian consumers. [ABSTRACT FROM AUTHOR]

4-methylimidazole (4-MEI) as the main by-product of many foods like drink colas, beverages, soy sauce, meats, candy, vinegar and caramel color which is formed in a high temperature following millard reaction. Other data revealed that 4-MEI is a neurotoxic and carcinogenic agent in animals but the obscure mechanistic pathway on the liver of wistar rats after two month administration. Therefore, sub-chronic effects of 4-MEI (32 µg kg−1–64 mg kg−1) were conducted on the cytotoxicity and inflammatory biomarkers in the liver and then histopathological changes were evaluated following oral administration. Our data revealed that 4-MEI exposure enhanced protein and lipid oxidation, and decreased reduced glutathione and total antioxidant level (FRAP) with histopathological changes in rats in higher doses of 320 µg kg−1. Our data explored the potentially toxic role of 4-MEI on the liver via induction of oxidative stress, mitochondrial dysfunction with negative impacts on glutathione and Frap level, and a raise in protein carbonylation and lipid peroxidation in the different doses of 4-MEI which leads to cell death signaling in the liver. Increased nitric oxide (NO) levels suggested the involvement of inflammation in 4-MEI mechanistic toxicity. Our data explored the potential hepatotoxic of 4-MEI by considering its possible role in oxidative stress, inflammation, and mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]