Enhancement of Vitamin C’s Protective Effect against Thimerosal-Induced Neurotoxicity in the Cerebral Cortex of Wistar Albino Rats: An In Vivo and Computational Study

Abstract

Vitamin C was examined to ameliorate the neurotoxicity of thimerosal (THIM) in an animal model (Wistar albino rats). In our work, oxidative and antioxidative biomarkers such as SOD, LPO, and GSH were investigated at various doses of THIM with or without concurrent vitamin C administration. Furthermore, the adverse effects of THIM on hepatic tissue and cerebral cortex morphology were examined in the absence or presence of associated vitamin C administration. Also, we studied the effect of vitamin C on the metallothionein isoforms (MT-1, MT-2, and MT-3) in silico and in vivo using the RT-PCR assay. The results showed that the antioxidant biomarker was reduced as the THIM dose was raised and vice versa. THIM-associated vitamin C reduced the adverse effects of the THIM dose. The computation studies demonstrated that vitamin C has a lower ΔG of −4.9 kcal/mol compared to −4.1 kcal/mol for THIM to bind to the MT-2 protein, which demonstrated that vitamin C has a greater ability to bind with MT-2 than THIM. This is due to multiple hydrogen bonds that exist between vitamin C and MT-2 residues Lys31, Gln23, Cys24, and Cys29, and the sodium ion represents key stabilizing interactions. Hydrogen bonds involve electrostatic interactions between hydrogen atom donors (e.g., hydroxyl groups) and acceptors (e.g., carbonyl oxygens). The distances between heavy atoms are typically 2.5−3.5 Å. H-bonds provide directed, highaffinity interactions to anchor the ligand to the binding site. The five H-bonds formed by vitamin C allow it to form a stable complex with MT, while THIM can form two H-bonds with Gln23 and Cys24. This provides less stabilization in the binding pocket, contributing to the lower affinity compared to vitamin C. The histopathological morphologies in hepatic tissue displayed an expansion in the portal tract and the hepatocytes surrounding the portal tract, including apoptosis, binucleation, and karyomegaly. The histopathological morphologies in the brain tissue revealed a significant decrease in the number of Purkinje cells due to THIM toxicity. Interestingly, THIM toxicity was associated with hemorrhage and astrogliosis. Both intracellular and vasogenic edema appeared as the concentrations of THIM rose. Finally, vitamin C ameliorated the adverse effect on the cerebral cortex in Wistar albino rats.

Glycyrrhizic Acid Nanoparticles Subside the Activity of Methicillin-Resistant Staphylococcus aureus by Suppressing PBP2a

“…The bacterial inoculums were diluted twice using a 100 mL stock solution of GA-NPs (500 µM/mL) in 100 mL of MHB. After that, a resazurin solution was added to each well, and they were all incubated at 37 • C for 24 h. Should the hue shift from purple to pink, it would suggest the presence of bacteria [19].…”

“…Penicillin-binding proteins play multiple roles in protein's transpeptidase (TPase) domain, contributing to the survival and growth of MRSA bacteria. The main function of PBP2 in MRSA strains is interchanged with that of PBP2A, which serves as a surrogate transpeptidase [19]. During this study, we prepared GA nanoparticles (GA-NPs) using the hydrothermal method and characterized them using physiochemical techniques.…”