Antioxidants and selenocompounds inhibit 3,5-dimethylaminophenol toxicity to human urothelial cells

Abstract

Exposure to alkyl anilines may lead to bladder cancer, which is the second most frequent cancer of the urogenital tract. 3,5-dimethylaniline is highly used in industry. Studies on its primary metabolite 3,5-dimethylaminophenol (3,5-DMAP) showed that this compound causes oxidative stress, changes antioxidant enzyme activities, and leads to death of different mammalian cells. However, there is no in vitro study to show the direct effects of 3,5-DMAP on human bladder and urothelial cells. Selenocompounds are suggested to decrease oxidative stress caused by some chemicals, and selenium supplementation was shown to reduce the risk of bladder cancer. The main aim of this study was to investigate whether selenocompounds organic selenomethionine (SM, 10 µmol/L) or inorganic sodium selenite (SS, 30 nmol/L) could reduce oxidative stress, DNA damage, and apoptosis in UROtsa cells exposed to 3,5-DMAP. 3,5-DMAP caused a dose-dependent increase in intracellular generation of reactive oxygen species, and its dose of 50 µmol/L caused lipid peroxidation, protein oxidation, and changes in antioxidant enzyme activities in different cellular fractions. The comet assay also showed single-strand DNA breaks induced by the 3,5-DMAP dose of 50 µmol/L, but no changes in double-strand DNA breaks. Apoptosis was also triggered. Both selenocompounds provided partial protection against the cellular toxicity of 3,5-DMAP. Low selenium status along with exposure to alkyl anilines can be a major factor in the development of bladder cancer. More mechanistic studies are needed to specify the role of selenium in bladder cancer.

Selenium in cereals: Insight into species of the element from total amount

“…SeMet acted as an antioxidant to prevent cholestasis‐induced liver damage and inflammation (Brzački et al., 2019), and it also alleviated T‐2 toxin (type A trichothecenes)‐induced oxidative stress, inflammatory response, intestinal barrier damage, and kidney injury (Liu, Dong, et al., 2020; Liu, Yang, et al., 2020). SeMet and selenite both reduced 3,5‐dimethylaminophenol‐induced oxidative stress, DNA damage, and apoptosis in human urothelial cells, and SeMet at a concentration of 10 μmol/L exerted protecting effect equal to that of selenite at a concentration of 30 μmol/L (Erkekoglu et al., 2019). SeMet supplementation resulted in a higher feed intake and higher levels of total Se, SELENOP, SeAlb, and SeMet in sow colostrum than selenite supplementation (Falk et al., 2019).…”

Effects of Atypical Neurotoxins on the Developing Fetal Brain

“…Accordingly, oxidation of alkyl anilines is generally regarded as a critical bioactivation. Indeed, studies have shown that the major metabolite of 3,5-DMA and 3,5-dimethylaminophenol (3,5-DMAP) is responsible for the ROS production, which contributes to the apoptotic cytotoxicity in mammalian cell lines [113,114]. Furthermore, a recent in vivo study has shown that 3,5-DMA-induced ROS production disrupts the dendrites patterning of the cortical cells and causes the abnormal cortical layer distribution in developing fetal brain [115].…”

Selenomethionine Alleviates Intestinal Ischemia Reperfusion Injury by Inhibiting Mitochondrion-mediated Apoptosis in Mice 

“…SeMet provides Se for the synthesis of selenoproteins such as Gpx1. Se-Met can enhance antioxidant capacity and reduce oxidative stress 13,14 .…”