Antioxidants and pentoxifylline as coadjuvant measures to standard therapy to improve prognosis of patients with pneumonia by COVID-19

Chavarría, Adrián Palacios; Vázquez, Rafael Ricardo Valdez; Cherit, José Guillermo Domínguez; Bello, Héctor Herrera; Suastegui, Humberto Castillejos; Moreno-Castañeda, Lidia; Estrada, Gabriela Alanís; Hernández, Fabián; González-Marcos, Omar; Saucedo-Orozco, Huitzilihuitl; Manzano-Pech, Linaloe; Márquez-Velasco, Ricardo; Guarner-Lans, Verónica; Pérez-Torres, Israel; Soto, Marí­a Elena

doi:10.1016/j.csbj.2021.02.009

Cited by 62 publications

(82 citation statements)

References 76 publications

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“…Fifteen FIASMAs [ 20 , 25 , 29 , 30 , 31 , 32 , 46 , 53 , 54 , 73 , 75 , 76 , 77 , 78 , 82 , 88 , 101 , 102 , 103 ] have been studied using epidemiological-clinical studies or case reports (amiodarone, amitriptyline, amlodipine, carvedilol, chlorpromazine, clomipramine, desloratadine, fluoxetine, fluvoxamine, hydroxyzine, loperamide, loratadine, melatonine, paroxetine, and sertraline). Among the 15 FIASMAs, only amlodipine [ 32 ] and fluvoxamine [ 75 ] were studied using randomized double-blind clinical studies (see Table 2 ).…”

Section: Update (16 June 2021) On Studies With Fiasmas In the Sars-cov-2 Infectionmentioning

confidence: 99%

Update on Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) in SARS-CoV-2 Infection

Loas

Corre

2021

Pharmaceuticals

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The SARS-CoV-2 outbreak is characterized by the need of the search for curative drugs for treatment. In this paper, we present an update of knowledge about the interest of the functional inhibitors of acid sphingomyelinase (FIASMAs) in SARS-CoV-2 infection. Forty-nine FIASMAs have been suggested in the treatment of SARS-CoV-2 infection using in silico, in vitro or in vivo studies. Further studies using large-sized, randomized and double-blinded controlled clinical trials are needed to evaluate FIASMAs in SARS-CoV-2 infection as off-label therapy.

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Section: Update (16 June 2021) On Studies With Fiasmas In the Sars-cov-2 Infectionmentioning

confidence: 99%

Update on Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) in SARS-CoV-2 Infection

Loas

Corre

2021

Pharmaceuticals

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“…This receptor induces inflammation and aggravates tissue damage. During acute inflammation, free radicals are generating that may lead to lipid hydroperoxides derived from the LOX pathway ( Chavarría et al, 2021 ). These hydroxyl acids are metabolites that derivate from LA and AA, and may be esterified into CT esters, triacylglycerol, and PL in oxLDL, oxHDL which may contribute to hypertriglyceridemia ( Sorokin et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that these PL could be used in the formation of both viral membrane and for reparation of the host’s own membrane after of the budding process. PL are also highly susceptible to oxidation by free radicals which results in oxidized PL (oxPL) and favor lipid peroxidation ( Chavarría et al, 2021 ). The oxPL are recognized as important bioactive lipid mediators playing an active role as modulators in signaling events in inflammation, immunity, infection, and biomarkers of atherosclerosis and other pathologies ( Rogero et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…The protocol was registered (TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 04570254). During the pre-treatment and post-treatment evaluation of the study ( Chavarría et al, 2021 ), we observed that the lipid levels were below the normal range since the admission of the patients. It was therefore considered that, in addition to the main objective, the evaluation if this decrease needed to be explored as part of the mechanism of damage by SARS-CoV-2.…”

Section: Methodsmentioning

confidence: 97%

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Alteration in the Lipid Profile and the Desaturases Activity in Patients With Severe Pneumonia by SARS-CoV-2

et al. 2021

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The kidnapping of the lipid metabolism of the host’s cells by severe acute respiratory syndrome (SARS-CoV-2) allows the virus to transform the cells into optimal machines for its assembly and replication. Here we evaluated changes in the fatty acid (FA) profile and the participation of the activity of the desaturases, in plasma of patients with severe pneumonia by SARS-CoV-2. We found that SARS-CoV-2 alters the FA metabolism in the cells of the host. Changes are characterized by variations in the desaturases that lead to a decrease in total fatty acid (TFA), phospholipids (PL) and non-esterified fatty acids (NEFAs). These alterations include a decrease in palmitic and stearic acids (p ≤ 0.009) which could be used for the formation of the viral membranes and for the reparation of the host’s own membrane. There is also an increase in oleic acid (OA; p = 0.001) which could modulate the inflammatory process, the cytokine release, apoptosis, necrosis, oxidative stress (OS). An increase in linoleic acid (LA) in TFA (p = 0.03) and a decreased in PL (p = 0.001) was also present. They result from damage of the internal mitochondrial membrane. The arachidonic acid (AA) percentage was elevated (p = 0.02) in the TFA and this can be participated in the inflammatory process. EPA was decreased (p = 0.001) and this may decrease of pro-resolving mediators with increase in the inflammatory process. The total of NEFAs (p = 0.03), PL (p = 0.001), cholesterol, HDL and LDL were decreased, and triglycerides were increased in plasma of the COVID-19 patients. Therefore, SARS-CoV-2 alters the FA metabolism, the changes are characterized by alterations in the desaturases that lead to variations in the TFA, PL, and NEFAs profiles. These changes may favor the replication of the virus but, at the same time, they are part of the defense system provided by the host cell metabolism in its eagerness to repair damage caused by the virus to cell membranes.

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“…More recently, it has been suggested that the supplementation of vitamin D, zinc, melatonin, and possibly additional nutraceuticals could reduce the risk and aid control of COVID-19 and a range of other viral infections [221]. Therefore, in the context of "antioxidant therapy", a cocktail with antioxidant supplements such as vitamins C and E, N-acetylcysteine, and melatonin in combination with the hemorrheologic agent pentoxifylline could contribute to the mitigation of the aggressive and lethal development COVID-19 [222]. Likewise, given the rich evidence that this extensive literature compiles and the international prestige of some of the personalities that bona fide endorse this clinical strategy, it is difficult for us to find resounding words and a new convincing voice to persuade public health dealers and professionals about the urgency of undertaking standardized clinical trials.…”

Section: Melatonin In Adjuvant Therapy Combination Against Sars-cov-2 Infectionmentioning

confidence: 99%

The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy

et al. 2021

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Viral infections constitute a tectonic convulsion in the normophysiology of the hosts. The current coronavirus disease 2019 (COVID-19) pandemic is not an exception, and therefore the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, like any other invading microbe, enacts a generalized immune response once the virus contacts the body. Melatonin is a systemic dealer that does not overlook any homeostasis disturbance, which consequently brings into play its cooperative triad, antioxidant, anti-inflammatory, and immune-stimulant backbone, to stop the infective cycle of SARS-CoV-2 or any other endogenous or exogenous threat. In COVID-19, the corporal propagation of SARS-CoV-2 involves an exacerbated oxidative activity and therefore the overproduction of great amounts of reactive oxygen and nitrogen species (RONS). The endorsement of melatonin as a possible protective agent against the current pandemic is indirectly supported by its widely demonstrated beneficial role in preclinical and clinical studies of other respiratory diseases. In addition, focusing the therapeutic action on strengthening the host protection responses in critical phases of the infective cycle makes it likely that multi-tasking melatonin will provide multi-protection, maintaining its efficacy against the virus variants that are already emerging and will emerge as long as SARS-CoV-2 continues to circulate among us.

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Antioxidants and pentoxifylline as coadjuvant measures to standard therapy to improve prognosis of patients with pneumonia by COVID-19

Abstract: Graphical abstract

Cited by 62 publications

References 76 publications

Update on Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) in SARS-CoV-2 Infection

Update on Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) in SARS-CoV-2 Infection

Alteration in the Lipid Profile and the Desaturases Activity in Patients With Severe Pneumonia by SARS-CoV-2

The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy

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