Efeitos da colchicina sobre estresse oxidativo, neuroinflamação e disfunção mitocondrial induzidos por lipopolissacarídeo (LPS) em linhagens celulares de astrócitos e PC12: implicações para modulação da via NRF-2

Abstract

Neurodegenerative diseases and psychiatric disorders share common pathological processes such as oxidative stress, inflammation, mitochondrial dysfunction, and cell death. The transcription factor Nrf2 regulates antioxidant and cytoprotective pathways, representing a promising therapeutic target. Colchicine, traditionally used in inflammatory diseases, has shown potential to activate Nrf2, but its effects on nervous system cells are still poorly understood. This study aimed to investigate the effects of colchicine, at low concentrations, on oxidative stress, inflammation, mitochondrial function, and cell death parameters in astrocytes and PC12 (pheochromocytoma) cells stimulated with LPS (lipopolysaccharide). Cell viability (MTT) was assessed in astrocytes and PC12 cells treated with colchicine. These cells were exposed to lipopolysaccharide (LPS) (50 µg/mL) to induce apoptosis, oxidative stress, inflammation, and mitochondrial dysfunction. They were then treated with colchicine (Col) (Col1: 0.312; Col2: 0.156 and Col3: 0.07815 µM) for evaluation intracellular ROS (DCFH-DA), (NO₂⁻) (Griess), mitochondrial membrane potential (Rhodamine 123), mitochondrial swelling, and cytokine release (TNF-α, IL-6 and IL-1β) by ELISA. Colchicine significantly reduced cytosolic oxidative stress in astrocytes (LPS+ Col2: 0.9482 ± 0.05592; LPS+Col3: 0.8801 ± 0.01104) and PC12 cells (LPS: 1.654 ± 0.01617; LPS+Col1: 0.9367 ± 0.006825; LPS+Col2: 0.6795 ± 0.01; LPS+Col3: 0.6541 ± 0.01782); and TNF-α in conditioned medium from astrocytes (LPS: 3.408 ± 0.3655; LPS+Col2: 0.9707 ± 0.2598). There was also significant restoration of mitochondrial membrane potential in PC12 cells (LPS: 0.6706 ± 0.02813; LPS+Col1: 1.177 ± 0.06531; LPS+Col2: 0.9941 ± 0.01699; LPS+Col3: 1.394 ± 0.03225) and decreased mitochondrial swelling in the same cell line (LPS: 0.1397 ± 0.0008337; LPS+Col1: 0.005867; LPS+Col2: 0.005571 ± 0.0006603; LPS+Col3: 0.002700 ± 0.0004502). The results indicated that colchicine exhibits antioxidant, anti-inflammatory, and mitochondrial-protective effects in astrocyte and PC12 cell lines, reinforcing its neuroprotective role in conditions associated with neuroinflammation.