Fig. 4.
Mitochondrial dysfunction in CIPN and role of its pharmacological modulation: the common factors associated with oxidative stress induced mitochondrial dysfunction are disruption of calcium homeostasis, increased mitochondrial outer membrane permeability (MOMP), defective mitochondrial ATP synthesis, alteration in the mitochondrial membrane potential (↓ΔΨm), induction of mPTP, release of Cyt c (since it loose its binding ability by oxidative induced damage to the cardiolipin), mitochondrial swelling etc. [26]. All these steps occur together or one orchestrates with other and forms a vicious cycle which further disrupts mitochondrial function. This finally leads to the cell death via apoptosis or necrosis. Pharmacological manipulation of mitochondrial toxicity with mitochondria-targeted antioxidants could help us to get the better therapeutic outcome in CIPN through alleviation of mitochondria mediated oxidative stress [20], [27], [38].