Potential roles of mitochondrial cofactors in the adjuvant mitigation of proinflammatory acute infections, as in the case of sepsis and COVID-19 pneumonia

Giovanni Pagano,Alex Lyakhovich,Carla Manfredi,Luca Tiano,Marco Trifuoggi,Federico V Pallardó

doi:10.1007/s00011-020-01423-0

Abstract

BackgroundThe 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.MethodsUsing 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.ResultsThe 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.ConclusionsThe 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.

Highlights

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]
This means that mitochondria may be dysfunctional and unable to cope with the hypermetabolic demands associated with COVID-19 sepsis
We have reported previously on the combined features of mitochondrial dysfunction (MDF), prooxidant state and prospective use of mitochondrial nutrients (MNs) in an extensive number of chronic, age-related or genetic disorders [6, 63–67]

Summary

Introduction

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]. The most recent work by Gibellini et al [48] shows a decrease in ATP and MDF levels in patients infected with SARS-CoV-2 This means that mitochondria may be dysfunctional and unable to cope with the hypermetabolic demands associated with COVID-19 sepsis. CARN, when tested in rat renal cells or cardiomyocytes, was found to enhance SOD2 expression and to counteract OS and inflammation [76, 77] Taken together, these studies of the in vitro MNassociated antioxidant effects provide a body of evidence suggesting a protective antioxidant action of MNs at the organismal level.

Conclusions

Compliance with ethical standards