Oenological tannins mitigate rotenone-induced mitochondrial impairments and oxidative stress, with concomitant detection of urolithin A in the brain.

Mitochondria are key organelles that supply energy to the brain, and their dysfunction contributes to neurotoxicity induced by environmental toxins such as rotenone. Recently, oenological tannins (OTs) and their colonic metabolite, urolithin A (UA), have been emphasized due to their potential neuroprotective activity. However, their role in counteracting toxin-induced mitochondrial impairments remains unclear. Therefore, this study aimed to investigate the administration of OTs to rotenone (ROT)-induced mitochondrial dysfunction and oxidative stress, key contributors to neurotoxicity. We measured mitochondrial membrane potential (MMP), the activity of mitochondrial complex I (Grishchuk et al.), and aldehyde dehydrogenase 2 (ALDH2) to assess mitochondria and protein carbonyl (PC) levels. We also checked the presence of UA in the brain. Our results indicate that the OTs treatment restored MMP, increased MCI and ALDH2 activity, and decreased PC content in ROT-induced rats. Furthermore, we confirmed the presence of UA in the brains of the animals. While its exact contribution to the observed mitochondrial effects remains undetermined, this finding suggests a potential role of the gut-derived metabolite in neuroprotection. Thus, we conclude that OTs administration attenuates mitochondria-related neurotoxicity. We call for further mechanistic studies and the putative contribution of metabolites, including UA, to the demonstrated mitoprotective effect of OTs treatment.