Epigenetic changes, in particular DNA methylation processes, play a role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM) linking genetic and environmental factors. To clarify this role, we have analyzed in patients with different duration of T2DM: (i) expression levels of methyl-CpG-binding domain protein 2 (MBD2) as marker of DNA methylation, and ii) methylation changes in 22 genes connected to cellular stress and toxicity. We have analyzedMBD2mRNA expression levels in16 patients and 12 controls and the methylation status of stress and toxicity genes in four DNA pools: (i) controls; (ii) newly-diagnosed T2DM patients; (iii) patients with T2DM duration of 5 years. TheMBD2expression levels were 10.4-times increased on average in T2DM patients compared to controls. Consistent increase in DNA methylation fraction with the increase in T2DM duration was observed inPrdx2andSCARA3genes, connected to oxidative stress protection and inBRCA1andTp53tumor-suppressor genes. In conclusion, increasedMBD2expression in patients indicated general dysregulation of DNA methylation in T2DM. The elevated methylation ofPrdx2andSCARA3genes suggests disturbance in oxidative stress protection in T2DM. The increased methylation ofBRCA1andTp53genes unraveled an epigenetic cause for T2DM related increase in cancer risk.

The toxin 6-hydroxydopamine (6-OHDA) is a highly oxidizable dopamine (DA) analog that is widely used for reproducing several cell processes identified in Parkinson’s disease (PD). Due to the close similarity of its neurotoxic mechanism to those of DA, it is suitable as a model for testing the effects of potentially neuroprotective drugs. This study aimed to evaluate the effect of alpha-lipoic acid (LA) on brain oxidative stress (OS) in unilateral intrastriatal (6-OHDA) injected rats. Forty male Wistar rats, four months old (220–260 g), were evaluated. Half of them received LA (35 mg/kg i.p.) from the start to the end of the experiment. On day 2 of the trial, ten LA-supplemented rats and ten non-LA-supplemented rats were subjected to the apomorphine test. Brain homogenates were evaluated for thiobarbituric acid-reactive substances (TBARS) and glutathione peroxidase (GPx) activity. The same evaluation procedures were repeated on day 14 with the remaining animals. An increased TBARS level and decreased GPx activity, suggestive for OS, were recorded in homogenates on day 14 vs. day 2 of the experiment in the 6-OHDA treated rats. The simultaneous application of LA mitigated these changes. Our study demonstrates that the low dose of LA could be of value for decreasing the OS of the neurotoxic 6-OHDA, supporting the need for further studies of the benefit of LA treatment in PD.