Indole-3-carbinol exerts neuroprotective effect in cerebral ischaemia/reperfusion through the modulation of Nrf2-mediated antioxidant responses and the restoration of chaperone activity

Cerebral ischaemia is the primary cause of stroke. The restoration of blood flow, known as reperfusion, has been observed to exacerbate the pathological changes caused by ischaemia and lead to a significant increase in the formation of reactive oxygen species. Cellular defense against reactive molecules is facilitated by the antioxidant system. The nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor is considered to be the primary regulator of this system. One of the exogenous antioxidants that has the potential to enhance the redox status in tissues experiencing oxidative stress is indole-3-carbinol (I3C). The objective of the present study was to analyze the transcriptional regulation of antioxidant enzyme functioning under conditions of I3C administration to rats with cerebral ischaemia/reperfusion injury (CIRI). The findings of this study demonstrated that the administration of I3C to rats with CIRI resulted in the normalization of the lactate/pyruvate ratio and the reduction of brain tissue damage. These outcomes could be attributed to the improvement of the redox status caused by the tested compound. Furthermore, I3C altered the activity of antioxidant enzymes and the number of Nrf2-positive neurons, leading to a shift towards control values. It has been demonstrated that I3C is also capable of restoring chaperone activity. This capacity may play a pivotal role in correcting dysfunction in the proteostasis system and in maintaining adequate protein folding during the course of a disease. Consequently, I3C demonstrated a neuroprotective effect in CIRI by normalizing oxidative status, regulating Nrf2-mediated antioxidant response, and enhancing chaperone activity.