Spectroscopic and molecular modeling studies on the interactions of N-Methylformamide with superoxide dismutase.

N-Methylformamide, a polar solvent has a wide industrial applications and it is well-known for hepatotoxicity. The interaction between NMF with superoxide dismutase, an antioxidant defense enzyme has been studied for the first time using spectroscopic methods including Fourier transform infrared (FT-IR) spectroscopy, Circular dichroism (CD) spectroscopy and UV-visible spectroscopy under simulative physiological conditions and also by molecular modelling. Fourier Transform Infra Red analysis showed that the change in peak positions and shapes revealed that the secondary structure of SOD had been changed by the interaction with NMF. The data of CD spectra also confirmed that NMF decreased the degree of secondary structure of SOD, which directly resulted in destabilization of enzyme. We studied the inhibitory effect of NMF on enzyme kinetics by pyrogallol autoxidation revealed that protein-ligand complex caused structural unfolding which resulted in enzymatic inhibition. Thus the spectral behaviour of superoxide dismutase provides data concerning its conformational changes in the presence of NMF. Furthermore, molecular docking was applied to explore the binding mode between the protein-ligand complex. This suggested that Asn54 and Val302 residues of dimeric protein were predicted to interact with NMF. The present study provides direct evidence at a molecular level to show that exposure to NMF cause perturbation in its structure and function.

Effect of acute exposure of N,N-dimethylformamide, an industrial solvent on lipid peroxidation and antioxidants in liver and kidney of rats.

N,N-Dimethylformamide (DMF), an industrial solvent widely used throughout the world is a known toxic compound. Here, we studied the effects of acute exposure of DMF on liver and kidney in rats. Rats were treated intraperitoneally with a single dose of DMF (1.5 g/kg) for 24 and 48 h. Hepatic and nephrotoxicity was confirmed based on the significant increase in the serum levels of aspartate amino transferase, alanine amino transferase, alkaline phosphatase, gamma-glutamyl transferase, urea, creatinine and electrolytes. Oxidative stress was assessed by determining the levels of lipid peroxidation (LPO) and antioxidants in liver and kidney. The LPO levels were elevated in both the tissues upon DMF exposure, whereas the activities of enzymatic antioxidants SOD, CAT and Gpx and non-enzymatic antioxidants (glutathione and vitamin C) were declined. The hepatic- and nephrotoxicity was further confirmed by the increasing incidence of inflammation in the histopathological studies. The findings indicate that acute exposure of DMF results in oxidative stress, antioxidant deficiency, attenuating liver and kidney marker enzymes, resulting in tissue inflammation and damage.