Hyperlipidemia and Obesity’s Role in Immune Dysregulation Underlying the Severity of COVID-19 Infection

Khatchadourian, Christopher; Sisliyan, Christina; Nguyen, Kevin; Poladian, Nicole; Tian, Qi; Tamjidi, Faraaz; Luong, Bao; Singh, Manpreet; Robison, Jeremiah; Venketaraman, Vishwanath

doi:10.3390/clinpract11040085

Cited by 3 publications

(2 citation statements)

References 116 publications

(135 reference statements)

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“…GSH affects the expression of cytokines, this has been established by many studies which show an imbalance between pro and anti-inflammatory cytokines in disease states such as diabetes and human immunodeficiency virus ( 67 ). In a study analyzing heart failure among rabbits, those treated with NAC showed greater levels of GSH and consequently decreased expression of the transcription factor NF-κB when compared to controls.…”

Section: Role Of Vitamin D and Glutathione In Decreasing Cytokine Sur...mentioning

confidence: 97%

Type 2 Diabetes Contributes to Altered Adaptive Immune Responses and Vascular Inflammation in Patients With SARS-CoV-2 Infection

et al. 2022

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SARS-CoV-2, which initially emerged in November of 2019, wreaked havoc across the globe by leading to clinical acute respiratory distress syndrome and continues to evade current therapies today due to mutating strains. Diabetes mellitus is considered an important risk factor for progression to severe COVID disease and death, therefore additional research is warranted in this group. Individuals with diabetes at baseline have an underlying inflammatory state with elevated levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines, both of which cause these individuals to have higher susceptibility to SARS- CoV2 infection. The detrimental effects of SARS-CoV-2 has been attributed to its ability to induce a vast cell mediated immune response leading to a surge in the levels of pro-inflammatory cytokines. This paper will be exploring the underlying mechanisms and pathophysiology in individuals with diabetes and insulin resistance making them more prone to have worse outcomes after SARS- CoV2 infection, and to propose an adjunctive therapy to help combat the cytokine surge seen in COVID-19. It will also look at the immunomodulatory effects of glutathione, an antioxidant shown to reduce immune dysregulation in other diseases; Vitamin D, which has been shown to prevent COVID-19 patients from requiring more intensive care time possibly due to its ability to decrease the expression of certain pro-inflammatory cytokines; and steroids, which have been used as immune modulators despite their ability to exacerbate hyperglycemia.

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Section: Role Of Vitamin D and Glutathione In Decreasing Cytokine Sur...mentioning

confidence: 97%

Type 2 Diabetes Contributes to Altered Adaptive Immune Responses and Vascular Inflammation in Patients With SARS-CoV-2 Infection

et al. 2022

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“…Our previous paper proved that CIGB-258 showed potent anti-inflammatory activity in the normolipidemic state [ 21 ]. However, inflammation is exacerbated more by hyperlipidemia and obesity, particularly in COVID-19 patients [ 28 ]. Non-survivors displayed elevated serum C-reactive protein, ferritin, and IL-6 levels upon hospital admission [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

CIGB-258 Exerts Potent Anti-Inflammatory Activity against Carboxymethyllysine-Induced Acute Inflammation in Hyperlipidemic Zebrafish via the Protection of Apolipoprotein A-I

Cho

Nam²,

Kim³

et al. 2023

IJMS

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Inflammation and atherosclerosis are intimately associated via the production of dysfunctional high-density lipoproteins (HDL) and modification of apolipoprotein (apo) A-I. A putative interaction between CIGB-258 and apoA-I was investigated to provide mechanistic insight into the protection of HDL. The protective activity of CIGB-258 was tested in the CML-mediated glycation of apoA-I. The in vivo anti-inflammatory efficacy was compared in paralyzed hyperlipidemic zebrafish and its embryo in the presence of CML. Treatment of CML induced greater glycation extent of HDL/apoA-I and proteolytic degradation of apoA-I. In the presence of CML, however, co-treatment of CIGB-258 inhibited the glycation of apoA-I and protected the degradation of apoA-I, exerting enhanced ferric ion reduction ability. Microinjection of CML (500 ng) into zebrafish embryos resulted in acute death with the lowest survivability with severe developmental defects with interleukin (IL)-6 production. Conversely, a co-injection of CIGB-258 or Tocilizumab produced the highest survivability with a normal development speed and morphology. In hyperlipidemic zebrafish, intraperitoneal injection of CML (500 μg) caused the complete loss of swimming ability and severe acute death with only 13% survivability 3 h post-injection. A co-injection of the CIGB-258 resulted in a 2.2-fold faster recovery of swimming ability than CML alone, with higher survivability of approximately 57%. These results suggest that CIGB-258 protected hyperlipidemic zebrafish from the acute neurotoxicity of CML. Histological analysis showed that the CIGB-258 group had 37% lower infiltration of neutrophils in hepatic tissue and 70% lower fatty liver changes than those of the CML-alone group. The CIGB-258 group exhibited the smallest IL-6 expression in the liver and the lowest blood triglyceride level. CIGB-258 displayed potent anti-inflammatory activity in hyperlipidemic zebrafish by inhibiting apoA-I glycation, promoting rapid recovery from the paralysis of CML toxicity and suppression of IL-6, and lowering fatty liver changes.

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Therapeutic Potentials of Black Seeds (Nigella sativa) in the Management of COVID-19 -A Review of Clinical and In-silico Studies

Maideen

Balasubramaniam²,

Muthusamy³

et al. 2023

AIA

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Background: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS, CoV-2), and patients with COVID-19 are managed mainly using repurposed conventional drugs, which target the viral entry and viral replication of SARS CoV-2 along with standard care and supportive therapy. Objective: This review article focuses on the potential benefits of black seeds (Nigella sativa) observed in clinical and in silico molecular docking studies of COVID-19. Methods: The literature was searched using databases such as LitCOVID, Web of Science, Google Scholar, bioRxiv, medRxiv, Science Direct, EBSCO, Scopus, EMBASE, and reference lists to identify published manuscripts or preprints related to the prevention or treatment of COVID-19 with black seeds (N. sativa) or their phytoconstituents. Results: Various clinical studies and in silico molecular docking studies determined that black seeds (N. sativa) and their bioactive phytoconstituents have potential activity against SARS CoV-2 infection. Conclusion: Patients with COVID-19 could be managed using black seeds (N. sativa) along with supportive care, which would speed up the recovery and decrease the mortality rate. More randomized controlled clinical trials would further establish the safety and efficacy of N. sativa in COVID-19 patients.

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Hyperlipidemia and Obesity’s Role in Immune Dysregulation Underlying the Severity of COVID-19 Infection

Cited by 3 publications

References 116 publications

Type 2 Diabetes Contributes to Altered Adaptive Immune Responses and Vascular Inflammation in Patients With SARS-CoV-2 Infection

Type 2 Diabetes Contributes to Altered Adaptive Immune Responses and Vascular Inflammation in Patients With SARS-CoV-2 Infection

CIGB-258 Exerts Potent Anti-Inflammatory Activity against Carboxymethyllysine-Induced Acute Inflammation in Hyperlipidemic Zebrafish via the Protection of Apolipoprotein A-I

Therapeutic Potentials of Black Seeds (Nigella sativa) in the Management of COVID-19 -A Review of Clinical and In-silico Studies

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