Sinapic acid ameliorates paracetamol-induced acute liver injury through targeting oxidative stress and inflammation

Rostami, Amir; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad

doi:10.1007/s11033-022-07251-1

Cited by 9 publications

(8 citation statements)

References 64 publications

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“…Proof of the principle above has been demonstrated by the increased hepatic immunoreactivity of p‐NF‐ĸB, iNOS, and INF‐β in the APAP‐intoxicated mice. As for APAP influence on NF‐ĸB, our findings were consistent with the reports by previous workers 11,37 . In the current study, the iNOS expression results support the data obtained by Jiang et al 38 .…”

Section: Discussionsupporting

confidence: 93%

Empagliflozin impact on experimentally induced acetaminophen toxicity: Imprint of mitochondrial dynamics, biogenesis, and cGAS/STING signal in amending liver insult

El‐Gohary,

Abdeen,

Ibrahim

et al. 2024

The FASEB Journal

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Acetaminophen (APAP) is one of the most clinically relevant medications associated with acute liver damage. A prolific deal of research validated the hepatoprotective effect of empagliflozin (EMPA); however, its effect on APAP‐induced hepatotoxicity has still not been investigated. In this study, the prospective hepatoprotective impact of EMPA against APAP‐induced hepatotoxicity was investigated. Twenty‐eight Balb‐C mice were assigned to four groups: control, APAP, EMPA10/APAP, and EMPA25/APAP. At the end of the experiment, serum hepatotoxicity biomarkers, MDA level, and GSH content were estimated. Hepatic mitofusin‐2 (MFN2), optic atrophy 1 (OPA1), dynamin‐related protein 1 (Drp1), and mitochondrial fission 1 protein (FIS1) were immunoassayed. PGC‐1α, cGAS, and STING mRNA expression were assessed by real‐time PCR. Histopathological changes and immunohistochemistry of INF‐β, p‐NF‐κB, and iNOS were evaluated. APAP treatment caused significant hepatic functional impairment and increased hepatic MDA levels, as well as a concomitant decrease in GSH content. Marked elevation in Drp1 and FIS1 levels, INF‐ß, p‐NF‐κB, and iNOS immunoreactivity, and reduction in MFN2 and OPA1 levels in the APAP‐injected group, PGC‐1α downregulation, and high expression of cGAS and STING were also documented. EMPA effectively ameliorated APAP‐generated structural and functional changes in the liver, restored redox homeostasis and mitochondrial dynamics balance, and enhanced mitochondrial biogenesis, remarkably diminished hepatic expression of cGAS and STING, and elicited a reduction in hepatic inflammation. Moreover, the computational modeling data support the interaction of APAP with antioxidant system‐related proteins as well as the interactions of EMPA against Drp1, cGAS, IKKA, and iNOS proteins. Our findings demonstrated for the first time that EMPA has an ameliorative impact against APAP‐induced hepatotoxicity in mice via modulation of mitochondrial dynamics, biogenesis, and cGAS/STING‐dependent inflammation. Thus, this study concluded that EMPA could be a promising therapeutic modality for acute liver toxicity.

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Section: Discussionsupporting

confidence: 93%

Empagliflozin impact on experimentally induced acetaminophen toxicity: Imprint of mitochondrial dynamics, biogenesis, and cGAS/STING signal in amending liver insult

El‐Gohary,

Abdeen,

Ibrahim

et al. 2024

The FASEB Journal

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“…Sinapic acid is abundantly found in different plant species, e.g., strawberries and cranberries, as well as cereals and vegetables; it is one of the most common compounds in the Brassicaceae family. Data found in the literature show that sinapic acid possesses antioxidant and anti-inflammatory properties [3], as well as anticancer [4], hepatoprotective [5], cardioprotective [6], renoprotective [6], neuroprotective [7], antidiabetic [8], anxiolytic [9], and antibacterial activity [10]. A review of the pharmacological and therapeutic applications of sinapic acid was recently published by Pandi et al [11].…”

Section: Methodsmentioning

confidence: 99%

Assessment of Pharmaco-Technological Parameters of Solid Lipid Nanoparticles as Carriers for Sinapic Acid

Russo

Greco

Sarpietro

2023

Micro

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Sinapic acid, 3,5-dimethoxyl-4-hydroxycinnamic acid, belonging to the class of hydroxycinnamic acids, shows antioxidant, anti-inflammatory, anticancer, hepatoprotective, cardioprotective, renoprotective, neuroprotective, antidiabetic, anxiolytic, and antibacterial activity. The aim of this work was to incorporate sinapic acid into solid lipid nanoparticles in order to improve its bioavailability. SLNs were prepared using the hot high-speed homogenization method. The pharmaco-technological properties and thermotropic profile of SLNs encapsulated with sinapic acid, as well as their interaction with biomembrane models, were evaluated. SLNs showed promising physicochemical properties and encapsulation efficiency, as well as a desirable release profile; moreover, they facilitated the interaction of sinapic acid with a biomembrane model made of multilamellar vesicles. In conclusion, this formulation can be used in further studies to assess its suitability to improve sinapic acid activity.

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“…Generally, APAP-induced oxidative stress and mitochondrial dysfunction play a central role in the pathogenesis of ALF (Jaeschke et al, 2012;Ahmad et al, 2021b). APAP overdose is a major cause leading to liver failure due to oxidative stress, mitochondrial and lysosomal dysfunction (Zubairi et al, 2014;Rostami et al, 2022). Treatment methods are also quite limited and are mainly represented by means with pronounced antioxidant and anti-inflammatory activity (Guo et al, 2019;Islam Shawon et al, 2024).…”

Section: Introductionmentioning

confidence: 99%

Plasma lipid profile and sex hormone levels in rabbits under paraceta-mol-induced oxidative stress

Vikulina,

Koshevoy,

Naumenko

et al. 2024

Ukr. Jour. of Vet. and Agr. Sci.

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Changes in the redox balance at different levels, which lead to the accumulation of toxic radicals against the background of a decrease in the content of redox-active compounds, i.e., a state of oxidative stress (OS), are considered the leading pathogenetic factor in pathological conditions. Processes of peroxide oxidation of biological substrates, especially cell membrane lipids and lipophilic compounds have both regulatory and pathological effects in the body of animals and humans. For now, it remains relevant to establish the regularities of interaction of metabolism during OS development. Among the large number of existing OS models, attention is drawn to those that can be reproduced in clinical practice, as a complication of treatment measures or an error in the medical strategy, due to a constant influence on peroxidation processes in the body. Important among such means is paracetamol (acetaminophen, APAP) – one of the most common antipyretic and analgesic drugs. In addition to the known hepato-, nephro- and neurotoxic effects of its long-term and/or excessive use, there are data on reproductive toxicity and disorders of lipid metabolism. Therefore, the aim of our work was to determine the lipid profile and the level of sex hormones in male rabbits during paracetamol-induced OS. The study was performed on male rabbits of the Khila breed. According to the principle of analogs, a control group (n = 12) was formed, which were kept on a standard diet, and an experimental group (n = 12), whose animals were simulated the state of OS by oral injection of a solution of paracetamol with food at a dose of 300 mg/kg of weight body once during 21 days. The following results were obtained by determining the dynamics of changes in biochemical indicators in the rabbit body during chronic injection of paracetamol: in the rabbits of the experimental group, after the injection of paracetamol, the level of diene conjugates was 63.0 % higher, and the content of thiobarbiturate-active products was 1.26 times higher (P ˂ 0.05). A decrease in the activity of the antioxidant defence system was also noted – the amount of reduced glutathione decreased by 35.4 %, and the activity of superoxide dismutase decreased by 25.6 % (P ˂ 0.05). The obtained changes were consistent with the comprehensive indicator of total antioxidant activity, which on the 21st day of the experiment was 34.1 % lower than the values of the control group (P ˂ 0.05). At the same time, the level of steroid hormones also changed during the study – the level of total testosterone gradually decreased (on the 21st day – by 22.8 %, and at the end of the experiment – by 30.9 %, P ˂ 0.05), while the level of 17β-estradiol had an upward trend and on the 21st day was higher than the control indicators by 10.7 % (P ˂ 0.05). Significant changes in lipid metabolism were found in male rabbits – the total cholesterol content on the 21st day of the experiment exceeded the data of control animals by 25.3 %, the level of triacylglycerols – by 42.3 %, and the content of low-density lipoprotein cholesterol also increased by 1.1 times (P ˂ 0.05), and the high-density lipoprotein cholesterol level, on the contrary, was reduced by 17.0 % (P ˂ 0.05). In general, the obtained results indicate the relationship between the development of OS with changes in lipid metabolism and the balance of sex hormones, which allows us to use the model of paracetamol-induced OS in rabbits for further research.

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Sinapic acid ameliorates paracetamol-induced acute liver injury through targeting oxidative stress and inflammation

Cited by 9 publications

References 64 publications

Empagliflozin impact on experimentally induced acetaminophen toxicity: Imprint of mitochondrial dynamics, biogenesis, and cGAS/STING signal in amending liver insult

Empagliflozin impact on experimentally induced acetaminophen toxicity: Imprint of mitochondrial dynamics, biogenesis, and cGAS/STING signal in amending liver insult

Assessment of Pharmaco-Technological Parameters of Solid Lipid Nanoparticles as Carriers for Sinapic Acid

Plasma lipid profile and sex hormone levels in rabbits under paraceta-mol-induced oxidative stress

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