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Monographs of fragrance chemicals and extracts that have caused contact allergy / allergic contact dermatitis
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Diethyl maleate is a colorless clear liquid; its odor type is fruity and its odor at 100% is described as ‘fruity banana citrus’ (www.thegoodscentscompany.com). It is prohibited by IFRA and the EU because of sensitization (8) and is not used anymore as fragrance.
Histological and biochemical investigation of the renoprotective effects of metformin in diabetic and prostate cancer model
Published in Toxicology Mechanisms and Methods, 2021
Pınar Koroglu-Aydın, Bertan Boran Bayrak, Ilknur Bugan, Omur Karabulut-Bulan, Refiye Yanardag
Reduced GSH, a cysteine containing natural tripeptide, is one of the most powerful intracellular antioxidant. It neutralizes reactive oxygen species (ROS) that causes oxidative stress, as well as detoxifies xenobiotics in cancer cells (Bansal and Simon, 2018). Contrastly, LPO levels as malondialdehyde (MDA) equivalent are useful marker for assessing the level of oxidative damage (Kangari et al. 2018). In the current study, GSH and LPO levels were measured in all experimental groups, so as to determine the level of oxidative damage resulting from diabetes and PCa in kidney tissues. Compared to control animals, GSH levels in diabetic, cancer, and DC group declined, whereas LPO levels were enhanced. Reduction of GSH and rising in LPO levels in diabetic, cancer, and DC groups may be a response to higher ROS formation. In a study assessing the effects of hydrogen peroxide and diethyl maleate on oxidative stress adaptation in aggressive PCa, it was demonstrated that GSH levels in human PCa cell lines (PC3 and HPV10) were lower, but were higher in normal prostate epithelium cells (RPWE1) when compared tocontrol group (Freitas et al. 2012). On the other hand, LPO levels were found to be almost twice in newly diagnosed breast cancer subjects as compared to control subjects (Kangari et al. 2018). In the present paper, GSH and LPO levels of metformin administed rats were found to be near normal levels (close to that of control animals). The reverting effect of metformin can be as a result of its anticancer and antioxidant properties (Zaidi et al. 2019).
Toxicity mechanism-based prodrugs: glutathione-dependent bioactivation as a strategy for anticancer prodrug design
Published in Expert Opinion on Drug Discovery, 2018
Xin-Yu Zhang, Adnan A. Elfarra
AVTP and AVTG indeed exhibited high reactivity toward GSH and excellent conversion rates to yield 6-MP and 6-TG in comparison with azathioprine (AZA), a prodrug of 6-MP that has long been used clinically (Figure 3) [60]. In incubation with GSH in buffer, the parent drugs were rapidly produced; approximately 60% of prodrugs were converted to 6-MP and 6-TG at 10 min [60]. When two human renal carcinoma cell lines were treated with AVTG, intracellular GSH concentrations rapidly decreased and reached the lowest at 20 min; at this time point the GSH concentrations were only ~10% of those before incubation. On the other hand, intracellular 6-TG concentrations increased over time and reached the highest at 10 min, and virtually kept constant from 10 to 20 min. The conversion to 6-TG was clearly GSH-dependent, because GSH-depleted cells by preincubation with diethyl maleate (DEM) showed much lower 6-TG concentrations in comparison to the cells untreated with DEM. Importantly, the intracellular 6-TG concentrations in AVTG-treated cells were approximately 7-fold higher than those observed in cells incubated with equimolar 6-TG concentrations, indicating that the prodrug delivered more 6-TG to cells than did 6-TG itself. Therefore, the prodrug significantly increased the efficiency of drug delivery. Interestingly, the prodrugs had comparable or lower IC50 values in more than 50 tumor cell lines in the National Cancer Institute’s anticancer drug screen, compared to their corresponding parent drugs (Table 1) [61]; in fact, their IC50 values in tumor cells tested were much lower than AZA [60].
Aflatoxin B1 reduces non-enzymatic antioxidant defenses and increases protein kinase C activation in the cerebral cortex of young rats
Published in Nutritional Neuroscience, 2018
Naiéli Schiefelbein Souto, Ana Claudia Monteiro Braga, Mayara Lutchemeyer de Freitas, Michele Rechia Fighera, Luiz Fernando Freire Royes, Mauro Schneider Oliveira, Ana Flávia Furian
It has been suggested that the deleterious effects of AFB1 are mediated by the increased production of reactive species, such as superoxide anion, hydroxyl radical, and hydrogen peroxide, at least in part, during the hepatic metabolism of the mycotoxin.30 However, only a few studies have investigated the effect of AFB1 on brain oxidative stress and antioxidant defenses. For instance, it has been shown that administration of AFB1 (25 mg/kg/p.o./90 days) does not alter the activity of glutathione reductase, catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) and malondialdehyde (MDA) levels in brain.31 A possible pro-oxidant effect of AFB1 (1250 μg/kg bw/day/14 days) was suggested by,32 who demonstrated an increase in SOD activity and a decreased GSH-Px activity in the brain, without concomitant alterations in MDA levels and CAT activity. Recently, Karabacak et al., 201533 also showed increased MDA levels, SOD, CAT, and GSH-Px activities in brain after AFB1 (400 μg/kg.bw/day/28days) exposition to Sprague–Dawley female rats. Altogether, the present study is in agreement with the fact that AFB1 exposure alters the brain redox state, since NPSH and ascorbic acid levels decrease after AFB1. Importantly, these results add to the literature because they indicate that even a single exposure to AFB1 is able to cause acute imbalance in the brain non-enzymatic antioxidant defenses. In this context, it is worth mentioning that depletion of glutathione storage has been proposed as one potential mechanism of aflatoxins,34 which is in line with the presently reported decrease in brain NPSH levels. Regarding this point, it is important to note that treatment with diethyl maleate, which decreases brain glutathione, potentiates the toxicity of 6-hydroxydopamine in rats.35 Moreover, the currently reported decrease in ascorbic acid may also be of importance, since this water-soluble antioxidant plays a pivotal role in the CNS, by supporting the regeneration of other antioxidants, such as vitamin E and GSH and also by modulation of neurotransmission.36 Accordingly, changes in the levels of ascorbic acid produce large impacts in brain physiology. For instance, it has been shown that heterozygous knockout mice for the sodium vitamin C transporter 2 present decreased levels of ascorbic acid in the brain, and it is highly susceptible to pentylenetetrazol-induced seizures and oxidative stress.37