Potential roles of mitochondrial cofactors in the adjuvant mitigation of proinflammatory acute infections, as in the cas
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Inflammation Research
REVIEW
Potential roles of mitochondrial cofactors in the adjuvant mitigation of proinflammatory acute infections, as in the case of sepsis and COVID‑19 pneumonia Giovanni Pagano1 · Carla Manfredi1 · Federico V. Pallardó2 · Alex Lyakhovich3,4 · Luca Tiano5 · Marco Trifuoggi1 Received: 11 August 2020 / Revised: 29 October 2020 / Accepted: 11 November 2020 © The Author(s) 2020
Abstract Background The mitochondrial cofactors α-lipoic acid (ALA), coenzyme Q10 (CoQ10) and carnitine (CARN) play distinct and complementary roles in mitochondrial functioning, along with strong antioxidant actions. Also termed mitochondrial nutrients (MNs), these cofactors have demonstrated specific protective actions in a number of chronic disorders, as assessed in a well-established body of literature. Methods Using PubMed, the authors searched for articles containing information on the utilization of MNs in inflammatory disorders as assessed from in vitro and animal studies, and in clinical trials, in terms of exerting anti-inflammatory actions. Results The retrieved literature provided evidence relating acute pathologic conditions, such as sepsis and pneumonia, with a number of redox endpoints of biological and clinical relevance. Among these findings, both ALA and CARN were effective in counteracting inflammation-associated redox biomarkers, while CoQ10 showed decreased levels in proinflammatory conditions. MN-associated antioxidant actions were applied in a number of acute disorders, mostly using one MN. The body of literature assessing the safety and the complementary roles of MNs taken together suggests an adjuvant role of MN combinations in counteracting oxidative stress in sepsis and other acute disorders, including COVID-19-associated pneumonia. Conclusions The present state of art in the use of individual MNs in acute disorders suggests planning adjuvant therapy trials utilizing MN combinations aimed at counteracting proinflammatory conditions, as in the case of pneumonia and the COVID-19 pandemic. Keywords Sepsis · Pneumonia · α-Lipoic acid · Coenzyme Q10 · Carnitine · COVID-19
Introduction
Responsible Editor: John Di Battista. * Giovanni Pagano [email protected] 1
Department of Chemical Sciences, Federico II Naples University, Via Cintia, 80126 Naples, Italy
2
Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia-INCLIVA, CIBERER, 46010 Valencia, Spain
3
Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain
4
Institute of Molecular Biology and Biophysics of the “Federal Research Center of Fundamental and Translational Medicine”, 630117 Novosibirsk, Russia
5
Department of Life and Environmental Sciences, Polytechnical University of Marche, 60100 Ancona, Italy
Acute pathological conditions display well-established links with oxidative stress (OS), through a number of different or complementary mechanistic features, as early studies have reported [1–4]. Fighting acute diseases has long been a target in medicine and over time has come to enc
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