Zinc Deficiency and Oxidative Stress Involved in Valproic Acid Induced Hepatotoxicity: Protection by Zinc and Selenium Supplementation

Valproic acid (VPA) is an antiepileptic drug, which its usage is limited due to its hepatotoxicity. The present study was conducted to investigate the efficacy of zinc (Zn) and selenium (Se), necessary trace elements, against VPA-induced hepatotoxicity in Wistar rats. The animals were divided into five groups: control, VPA 200 mg/kg, VPA + Zn (100 mg/kg), VPA + Se (100 mg/kg), and VPA + Zn + Se. The administration of VPA for four consecutive weeks resulted in decrease in serum level of Zn in rats. Also, an increase in liver marker enzymes (ALT and AST) and also histological changes in liver tissue were shown after VPA administration. Oxidative stress was evident in VPA group by increased lipid peroxidation (LPO), protein carbonyl (PCO), glutathione (GSH) oxidation, and reducing total antioxidant capacity. Zn and Se (100 mg/kg) administration was able to protect against deterioration in liver enzyme, abrogated the histological change in liver tissue, and suppressed the increase in oxidative stress markers. Zn and combination of Zn plus Se treatment showed more protective effects than Se alone. These results imply that Zn and Se should be suggested as effective supplement products for the prevention of VPA-induced hepatotoxicity.     

Monitoring mitochondrial translation in living cells

Mitochondria possess a small genome that codes for core subunits of the oxidative phosphorylation system and whose expression is essential for energy production. Information on the regulation and spatial organization of mitochondrial gene expression in the cellular context has been difficult to obtain. Here we devise an imaging approach to analyze mitochondrial translation within the context of single cells, by following the incorporation of clickable non‐canonical amino acids. We apply this method to multiple cell types, including specialized cells such as cardiomyocytes and neurons, and monitor with spatial resolution mitochondrial translation in axons and dendrites. We also show that translation imaging allows to monitor mitochondrial protein expression in patient fibroblasts. Approaching mitochondrial translation with click chemistry opens new avenues to understand how mitochondrial biogenesis is integrated into the cellular context and can be used to assess mitochondrial gene expression in mitochondrial diseases.     

Investigation of intermolecular hydrogen bond interactions in crystalline l-Cysteine by DFT calculations of the oxygen-17, nitrogen-14, and hydrogen-2 EFG tensors and AIM analysis

A systematic computational study is carried out to investigate hydrogen bond (HB) interactions in the real crystalline structures of l-Cysteine at 30 and 298 K by density functional theory (DFT) calculations of electric field gradient (EFG) tensors at the sites of O-17, N-14, and H-2 nuclei. One-molecule (monomer) and nine-molecule (cluster) models of l-Cysteine are created by available crystal coordinates at both temperatures and the EFG tensors are calculated for both models to indicate the effect of HB interactions on the tensors. The calculated EFG tensors at the level of B3LYP and B3PW91 DFT methods and 6-311++G?? and cc-pVTZ basis sets are converted to those experimentally measurable nuclear quadrupole resonance (NQR) parameters i.e. quadrupole coupling constants (qcc) and asymmetry parameters (η_Q). The evaluated NQR parameters reveal that the EFG tensors of ¹⁷O, ¹⁴N, and ²H are influenced and show particular trends from monomer to the target molecule in the cluster due to the contribution of target molecule to classic N–H…O, and non-classic S–H…O and S–H…S types of HB interactions. On the other hand, atoms in molecules (AIM) analyses confirm the presence of HB interactions and rationalize the observed EFG trends. The results indicate different contribution of various nuclei to HB interactions in the cluster where O2 and N1 have major contributions. The EFG tensors as well as AIM analysis at the H6 site show that the N1-H6…O2 HB undergoes a significant change from 30 to 298 K where changes in other N–H…O interactions are almost negligible. There is a good agreement between the calculated ¹⁴N NQR parameters and reported experimental data.