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Hypoxia-induced oxidative stress contributes to neuronal damage leading to many neurodegenerative disorders. Hypoxia promotes many downstream effectors such as hypoxia-inducible factor-1α (HIF-1α) in order to restore respiratory homeostasis due to low oxygen availability and increased ROS. Use of histone deacetylase (HDAC) inhibitors may modulate hypoxia-induced neuronal cell damage.  In this study, we used two chemically diverse HDAC inhibitors to investigate their effect on hypoxia-exposed neuronal cells. Human pluripotent NT-2 stem cell-derived neuronal differentiated cells were exposed to CoCl2 pre-treatment for 6h to induce hypoxia, prior to supplementation of HDAC inhibitor (SAHA or MGCD0103). Treatment with HDAC inhibitor improved cell viability in hypoxia-induced neuronal cells. The increased HIF1α expression in hypoxia-induced neuronal cells was blunted by these HDAC inhibitors with a concomitant decrease in ROS production. CoCl2 treatment caused an increase in IL-1β, which was significantly inhibited by these HDAC inhibitors. Furthermore, apoptosis induced in these CoCl2 treated neuronal cells was mitigated by SAHA as well MGCD0103 suggesting that these HDAC inhibitors are capable of reducing cellular toxicity, inflammation and apoptosis, and thus, could be beneficial as therapeutic molecules for many neuropathological conditions.

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Fishes are excellent subjects for the study of the mutagenic and carcinogenic potential of contaminants present in water. Herbicides are one of the toxic contaminants that cause lethal effects in fish. In this context, the present study was designed to study the sub‐lethal toxic effect (low dose [LD] 25 mg/L, medium dose‐50 mg/L, and high dose [HD] 100 mg/L) of a commonly used herbicide, pyrazosulfuron ethyl (PE), on erythrocytes of tilapia. The genotoxic effect was studied to understand the sub‐lethal potential by means of (a) the nuclear abnormalities, including the micronucleus (MN) frequency; (b) further, each stage of the cell cycle was analysed using flow cytometry and (c) finally, the targets of PE was deciphered using in silico analysis. The results showed that there were significant effects of time (7 and 14 days) and doses in the increase in the frequency of MN in erythrocytes of fish treated with PE, compared to the control group. After exposing fish to PE for 7 and 14 days, there was a proportional increase in the frequency of the apoptotic population of erythrocytes for LD to HD. During both time exposures (7 and 14 days), the highest cell death was accounted for in HD. Moreover, the majority of the cells showed a dysregulated cell cycle in the G1 phase in all the treated groups of PE, compared to the control group. This study showed that PE might initiate genotoxicity in non‐target species (tilapia) of the aquatic ecosystem near agricultural fields.