Unraveling the intrinsic and photodynamic effects of aluminum chloride phthalocyanine on bioenergetics and oxidative state in rat liver mitochondria

Previous research has revealed that mitochondria are an important target for photodynamic therapy (PDT), which might be employed as a therapeutic approach for several malignancies, including hepatocellular carcinoma (HCC). In this study, we investigated both intrinsic toxicity and photodynamic effects of the photosensitizer (PS) aluminum chloride phthalocyanine (AlClPc) on mitochondrial functions. Several aspects of mitochondrial bioenergetics, structure, and oxidative state were investigated in the isolated mitochondria obtained from rat liver by differential centrifugation. Additionally, experiments were conducted to demonstrate the intrinsic and photodynamic effects of AlClPc on the viability of HepG2 cells. AlClPc interacted with mitochondria regardless of photostimulation; however, at the maximum utilized concentration (40 μM), photostimulation reduced its interaction with mitochondria. Although AlClPc hindered catalase (CAT) and glutathione reductase (GR) activities intrinsically, it had no discernable capacity to generate oxidative stress or impact bioenergetics in mitochondria without photostimulation, as one would anticipate from an ideal PS. When exposed to light, however, AlClPc had a substantially unfavorable influence on mitochondrial function, strengthening its intrinsic inhibitory action on CAT, producing oxidative stress, and jeopardizing mitochondrial bioenergetics. In terms of oxidative stress parameters, AlClPc induced lipid peroxidation and decreased the level of reduced glutathione (GSH) in mitochondria. Regarding bioenergetics, AlClPc promoted oxidative phosphorylation uncoupling and photodynamic inactivation of complex I, complex II, and the F_oF₁–ATP synthase complex, lowering mitochondrial ATP production. Lastly, AlClPc exhibited a concentration-dependent decrease in the viability of HepG2 cells, regardless of the presence or absence of photostimulation. While the harmful photodynamic effects of AlClPc on mitochondrial bioenergetics hold promise for treating HCC and other malignancies, the inherent toxic impacts on HepG2 cells underscore the need for caution in its application for this purpose.