A new treatment approach: Melatonin and ascorbic acid synergy shields against sepsis-induced heart and kidney damage in male rats

Üstündağ, Hilal; Doğanay, Songül; Kalındemirtaş, Ferdane Danışman; Demir, Özlem; Huyut, Mehmet Tahir; Kurt, Nezahat; Özgeriş, Fatma Betül; Akbaba, Özge

doi:10.1016/j.lfs.2023.121875

Cited by 13 publications

(7 citation statements)

References 48 publications

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“…Historically, Vit C has been studied extensively for its antioxidant properties. Its role in combating oxidative stress and inflammation has been corroborated by several studies in the past 5,21,25 . Similarly, CoQ10, an endogenously produced lipid-soluble component, has shown significant potential in cellular energy production and acts as a strong antioxidant, defending against oxidative damage 41 .…”

Section: Discussionmentioning

confidence: 72%

“…However, during sepsis, this production is overwhelmingly amplified 46 . Historically, increased lipid peroxidation has been recorded in septic www.nature.com/scientificreports/ patients 47 , in juxtaposition with a decline in cardinal antioxidant enzymes 5 . This escalated oxidant milieu wreaks havoc at the cellular level in cardiac tissues, damaging proteins, lipids, and nucleic acids, culminating in severe endothelial dysfunction, which is especially detrimental in the context of heart health 48,49 .…”

Section: Discussionmentioning

confidence: 99%

“…Among the affected organs, the cardiovascular system is subjected to severe stress during sepsis, often culminating in what is referred to as septic cardiomyopathy, a finding well-supported by pre-clinical research 2 , 3 . This cardiac dysfunction, resulting in both direct and indirect damage to the heart, is a multifactorial process, stemming from various pathophysiological mechanisms that operate during sepsis, as demonstrated in both animal models and human studies 4 , 5 .…”

Section: Introductionmentioning

confidence: 99%

“…As a combination, these agents may offer a more comprehensive approach to modulating the intricate pathophysiological mechanisms underlying sepsis and associated cardiac dysfunction. This potential stems from their joint capacity to scavenge ROS, bolster the antioxidant defense system, and reduce inflammation, thereby potentially improving cardiac function and overall outcomes in sepsis, as evidenced by both pre-clinical and clinical research 5,22,23 .Previous studies have extensively explored the effects of Vit C and CoQ10 on sepsis-induced cardiac injury 17,18,21,24,25 . However, these investigations predominantly focused on their individual impacts rather than their combined efficacy.…”

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confidence: 99%

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Investigating the individual and combined effects of coenzyme Q10 and vitamin C on CLP-induced cardiac injury in rats

Üstündağ,

Demir,

Huyut

et al. 2024

Sci Rep

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Sepsis-induced cardiac injury represents a major clinical challenge, amplifying the urgency for effective therapeutic interventions. This study aimed to delve into the individual and combined prophylactic effects of Vitamin C (Vit C) and Coenzyme Q10 (CoQ10) against inflammatory heart injury in a cecal ligation and puncture (CLP) induced polymicrobial sepsis rat model. Thirty adult female Sprague–Dawley rats were randomly divided into five groups: Control, CLP, Vitamin C, CoQ10, and Vit C + CoQ10, each consisting of six rats. Treatments were administered orally via gavage for 10 days prior to the operation. Eighteen hours post-sepsis induction, the animals were euthanized, and specimens were collected for analysis. The study examined variations in oxidative (TOS, OSI, MDA, MPO) and antioxidative markers (TAS, SOD, CAT, GSH), histopathological changes, inflammatory cytokine concentrations (TNF-α, IL-1β), nitric oxide (NO) dynamics, and cardiac indicators such as CK-MB. Impressively, the combined regimen markedly diminished oxidative stress, and antioxidative parameters reflected notable enhancements. Elevated NO levels, a central player in sepsis-driven inflammatory cascades, were effectively tempered by our intervention. Histological examinations corroborated the biochemical data, revealing diminished cardiac tissue damage in treated subjects. Furthermore, a marked suppression in pro-inflammatory cytokines was discerned, solidifying the therapeutic potential of our intervention. Interestingly, in certain evaluations, CoQ10 exhibited superior benefits over Vit C. Collectively, these findings underscore the potential therapeutic promise of Vit C and CoQ10 combination against septic cardiac injuries in rats.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Investigating the individual and combined effects of coenzyme Q10 and vitamin C on CLP-induced cardiac injury in rats

Üstündağ,

Demir,

Huyut

et al. 2024

Sci Rep

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“…The study by Üstündağ et al. showcased that such a combined treatment reduced inflammation and cellular damage markers, improved NO, and vascular endothelial growth factor (VEGF) levels, alongside an increased SIRT1 expression, indicating a synergistic role in alleviating sepsis-induced inflammation, cellular damage, and oxidative stress - an assertion confirmed through histopathological analyses of the heart and kidneys ( 159 ).…”

Section: Drugs Targeting the Sirts In Sepsis-induced Modsmentioning

confidence: 96%

The role and therapeutic potential of SIRTs in sepsis

You,

Li,

Chong

2024

Front. Immunol.

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Sepsis is a life-threatening organ dysfunction caused by the host’s dysfunctional response to infection. Abnormal activation of the immune system and disturbance of energy metabolism play a key role in the development of sepsis. In recent years, the Sirtuins (SIRTs) family has been found to play an important role in the pathogenesis of sepsis. SIRTs, as a class of histone deacetylases (HDACs), are widely involved in cellular inflammation regulation, energy metabolism and oxidative stress. The effects of SIRTs on immune cells are mainly reflected in the regulation of inflammatory pathways. This regulation helps balance the inflammatory response and may lessen cell damage and organ dysfunction in sepsis. In terms of energy metabolism, SIRTs can play a role in immunophenotypic transformation by regulating cell metabolism, improve mitochondrial function, increase energy production, and maintain cell energy balance. SIRTs also regulate the production of reactive oxygen species (ROS), protecting cells from oxidative stress damage by activating antioxidant defense pathways and maintaining a balance between oxidants and reducing agents. Current studies have shown that several potential drugs, such as Resveratrol and melatonin, can enhance the activity of SIRT. It can help to reduce inflammatory response, improve energy metabolism and reduce oxidative stress, showing potential clinical application prospects for the treatment of sepsis. This review focuses on the regulation of SIRT on inflammatory response, energy metabolism and oxidative stress of immune cells, as well as its important influence on multiple organ dysfunction in sepsis, and discusses and summarizes the effects of related drugs and compounds on reducing multiple organ damage in sepsis through the pathway involving SIRTs. SIRTs may become a new target for the treatment of sepsis and its resulting organ dysfunction, providing new ideas and possibilities for the treatment of this life-threatening disease.

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Molecular mechanisms of resveratrol and its silver nanoparticle conjugate in addressing sepsis-induced lung injury

Üstündağ,

Kara,

Doğanay

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Sepsis is a life-threatening condition characterized by a systemic inflammatory response to infection. Despite extensive research on its pathophysiology, effective therapeutic approaches remain a challenge. This study investigated the potential of resveratrol (RV) and silver nanoparticle–enhanced resveratrol (AgNP-RV) as treatments for sepsis-induced lung injury using a rat model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The study focused on evaluating changes in oxidative status (TAS, TOS, and OSI) and the expression of inflammatory and apoptotic markers (IL-1β, TNF-α, P2X7R, TLR4, Caspase-3, and Bcl-2) in lung tissue. Both RV and AgNP-RV demonstrated potential in mitigating oxidative stress, inflammation, and apoptosis, with AgNP-RV exhibiting greater efficacy than RV alone (p < 0.05). These findings were corroborated by histopathological analyses, which revealed reduced tissue damage in the RV- and AgNP-RV-treated groups. Our study highlights the therapeutic potential of RV and, particularly, AgNP-RV in combating sepsis-induced oxidative stress, inflammation, and apoptosis. It also underscores the promise of nanoparticle technology in enhancing therapeutic outcomes. However, further investigations are warranted to fully understand the mechanisms of action, especially concerning the role of the P2X7 receptor in the observed effects. Nonetheless, our research suggests that RV and AgNP-RV hold promise as novel strategies for sepsis management.

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A new treatment approach: Melatonin and ascorbic acid synergy shields against sepsis-induced heart and kidney damage in male rats

Cited by 13 publications

References 48 publications

Investigating the individual and combined effects of coenzyme Q10 and vitamin C on CLP-induced cardiac injury in rats

Investigating the individual and combined effects of coenzyme Q10 and vitamin C on CLP-induced cardiac injury in rats

The role and therapeutic potential of SIRTs in sepsis

Molecular mechanisms of resveratrol and its silver nanoparticle conjugate in addressing sepsis-induced lung injury

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