In vitro beneficial effects of N-acetylcysteine and Coenzyme Q10 in Niemann-Pick type C patient-derived fibroblasts

Background: Niemann Pick type C (NP-C) is an inborn error of metabolism (IEM), classified as a lysosomal storage disease (LSD) caused by a dysfunction in NPC transport protein, that leads to intracellular accumulation of non-esterified cholesterol and other lipids. Clinical manifestations are ample, with visceral and neurological symptoms. Studies demonstrated the influence of oxidative stress and inflammation in IEM, as well as in animal models of NP-C disease, and the possible beneficial effects of antioxidant complementary therapy for this disease. Methods: In this way, we aimed to investigate the in vitro effect of N-acetylcysteine (NAC) and Coenzyme Q10 (CoQ10) in patients-derived fibroblasts. We performed an in vitro study with antioxidants NAC (1 mM and 2.5 mM) and CoQ10 (5 µM and 10 µM), and we determined its effect on inflammatory parameters, as well as in cholesterol accumulation. This study was performed in line with the principles of the Declaration of Helsinki and the project was approved by the Research Ethics Committee of the Hospital de Clínicas de Porto Alegre (CEP/HCPA 2018-0648). Results: Both treatments, NAC and CoQ10, showed good results in the evaluated parameters, reducing the intracellular accumulation of non-esterified cholesterol [F(5, 15)= 6.780; p<0.05] [F(5, 15)= 6.780; p<0.05]. Although the mechanism of this effect is not completely clear, it can be related to restoration in lipid traffic and a decrease in oxidative stress caused by the antioxidants. NAC also demonstrated inflammatory protection, since the pro-inflammatory cytokines were reduced in fibroblasts from NP-C patients after the in vitro treatment IL-6[F (2, 8)= 4.816, p<0.05] and TNF-α [F(2, 7)= 4.940, p<0.05]. Conclusion: Taken together our results indicate the potential of antioxidant therapy for NP-C patients, however in vivo studies are still needed to confirm these results.