New potential biomarkers of acetaminophen-induced hepatotoxicity

Siemionow, Katarzyna; Teul, Joanna; Drągowski, Paweł; Pałka, Jerzy; Miltyk, Wojciech

doi:10.1016/j.advms.2016.05.001

Cited by 12 publications

(7 citation statements)

References 45 publications

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“…Holmberg et al [32] reporting that the mean APRI values rose significantly with successive fibrosis levels in agreement with Ansar et al [33]. This finding might be due to a reduction in AST clearance with increasing in its release as liver fibrosis progress [34]. The mitochondrial injury could responsible for the marked release of AST (mitochondria and cytoplasm) to ALT during advanced liver disease as recorded by Okuda et al [35].…”

Section: Discussionsupporting

confidence: 74%

Biochemical and molecular study on the beneficial effect of Solubilized coenzyme Q10 on thioacetamide-induced liver fibrosis in adult male rats

Abd-Elmoniem

Zaki²

2021

Egypt. J. Chem.

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The present work aimed to evaluate the combined therapeutic effect of both solubilized Coenzyme Q10 and Silymarin on thioacetamide (TAA) induced liver injury. A total of thirty adult male albino rats, weighing 200±10 g were allocated into five groups. Hepatic injury was induced by Thioacetamide (TAA) 20 mg/ kg b wt for 28 days by intraperitoneal injection twice a week. On the other hand, solubilized Coenzyme Q10 (20 mg/kg) & Silymarin (50 mg/kg) were taken orally for 28 days. Upon using the aspartate and platelet ratio index (APRI) & aspartate aminotransferase-alanine aminotransferase ratio (AAR), the TAA group recording the highest values while treatments using Coenzyme Q10 and or Silymarin could decrease theirs values near the control one. However, solubilized CoQ10 could attenuate liver injury induced by TAA via balanced oxidative stress symbols (GSH, GSSG), NO level, and down-regulation gene expression of fibrotic markers TGF-β, collagen-1α, and, TIMP1 as well as enhanced the expression for MMP2 and cytochrome P 450 (CYP 2E1& CYP 3A2). Collectively, solubilized CoQ10 singly or combined with Silymarin showed higher therapeutic impacts more than or equivalents to Silymarin singly treatment for liver fibrosis induced by TAA.

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Section: Discussionsupporting

confidence: 74%

Biochemical and molecular study on the beneficial effect of Solubilized coenzyme Q10 on thioacetamide-induced liver fibrosis in adult male rats

Abd-Elmoniem

Zaki²

2021

Egypt. J. Chem.

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“…However, a fraction of AAP undergoes metabolization by the cytochrome P 450 system, generating the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) which, under normal conditions, is conjugated with GSH and eliminated. Nonetheless, increased NAPQI production results in the depletion of GSH and, consequently, oxidative liver damage [ 96 ]. Thus, we investigated for the first time the possible protective effect of Ro on AAP-induced hepatotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Rosemary (Rosmarinus officinalis L.) Glycolic Extract Protects Liver Mitochondria from Oxidative Damage and Prevents Acetaminophen-Induced Hepatotoxicity

et al. 2023

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Rosmarinus officinalis L. (rosemary) is an aromatic culinary herb. Native to the Mediterranean region, it is currently cultivated worldwide. In addition to its use as a condiment in food preparation and in teas, rosemary has been widely employed in folk medicine and cosmetics. Several beneficial effects have been described for rosemary, including antimicrobial and antioxidant activities. Here, we investigated the mechanisms accounting for the antioxidant activity of the glycolic extract of R. officinalis (Ro) in isolated rat liver mitochondria (RLM) under oxidative stress conditions. We also investigated its protective effect against acetaminophen-induced hepatotoxicity in vivo. A crude extract was obtained by fractionated percolation, using propylene glycol as a solvent due to its polarity and cosmeceutical compatibility. The quantification of substances with recognized antioxidant action revealed the presence of phenols and flavonoids. Dereplication studies carried out through LC-MS/MS and GC-MS, supported by The Global Natural Product Social Molecular Networking (GNPS) platform, annotated several phenolic compounds, confirming the previous observation. In accordance, Ro decreased the production of reactive oxygen species (ROS) elicited by Fe2+ or t-BOOH and inhibited the lipid peroxidation of mitochondrial membranes in a concentration-dependent manner in RLM. Such an effect was also observed in liposomes as membrane models. Ro also prevented the oxidation of mitochondrial protein thiol groups and reduced glutathione (GSH). In model systems, Ro exhibited a potent scavenger activity toward 2,2′-diphenyl-1-picrylhydrazyl (DPPH) radicals and superoxide anions. It also demonstrated an Fe2+ chelating activity. Moreover, Ro did not exhibit cytotoxicity or dissipate the mitochondrial membrane potential (∆Ψ) in rat liver fibroblasts (BRL3A cells). To evaluate whether such antioxidant protective activity observed in vitro could also be achieved in vivo, a well-established model of hepatotoxicity induced by acute exposure to acetaminophen (AAP) was used. This model depletes GSH and promotes oxidative-stress-mediated tissue damage. The treatment of rats with 0.05% Ro, administered intraperitoneally for four days, resulted in inhibition of AAP-induced lipid peroxidation of the liver and the prevention of hepatotoxicity, maintaining alanine and aspartate aminotransferase (ALT/AST) levels equal to those of the normal, non-treated rats. Together, these findings highlight the potent antioxidant activity of rosemary, which is able to protect mitochondria from oxidative damage in vitro, and effects such as the antioxidant and hepatoprotective effects observed in vivo.

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“…The enzymes ALT and AST are considered good indicators of liver function and can be applied as predictive biomarkers for possible toxicity. Generally, damage to the hepatic parenchyma causes an elevation of both enzymes in blood (Siemionow et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Tyramine exerts hypolipidemic and anti-obesity effects in vivo

Morais

Melo

Dantas

et al. 2022

Braz. J. Pharm. Sci.

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Obesity and dyslipidemia are conditions often associated with cardiovascular risk, inflammation, oxidative stress, and death. Thus, a new approach has been highlighted to promote research and development of pharmacological tools derived from natural sources. Among the most widely studied groups of substances, polyphenols such as tyramine stand out. This study investigated hypolipidemic and anti-obesity properties of tyramine. Oral toxicity evaluation, models of dyslipidemia and obesity were used. To induce dyslipidemia, Poloxamer-407 (P-407) was administered intraperitoneally. In the hypercholesterolemic and obesity model, specific diet and oral tyramine were provided. After 24h of P-407 administration, tyramine 2 mg/kg (T2) decreased triglycerides (TG) (2057.0 ± 158.5 mg/dL vs. 2838 ± 168.3 mg/dL). After 48h, TG were decreased by T2 (453.0 ± 35.47 vs. 760.2 ± 41.86 mg/dL) and 4 mg/kg (T4) (605.8 ± 26.61 760.2 ± 41.86 mg/dL). T2 reduced total cholesterol (TC) after 24h (309.0 ± 11.17 mg/dL vs. 399.7 ± 15.7 mg/dL); After 48h, 1 mg/kg (T1) (220.5 ± 12.78 mg/dL), T2 (205.8 ± 7.1 mg/dL) and T4 (216.8 ± 12.79 mg/dL), compared to P-407 (275.5 ± 12.1 mg/dL). The treatment decreased thiobarbituric acid reactive substances and nitrite in liver, increased superoxide dismutase, reduced the dietinduced dyslipidemia, decreasing TC around 15%. Tyramine reduced body mass, glucose, and TC after hypercaloric feed. Treatment with 5 mg/L (0.46 ± 0.04 ng/dL) and 10 mg/L (0.44 ± 0.02 ng/dL) reduced plasma insulin (1.18 ± 0.23 ng/dL). Tyramine increased adiponectin at 5 mg/L (1.02 ± 0.02 vs. 0.83 ± 0.02 ng/mL) and 10mg/L (0.96 ± 0.04 ng/mL). In conclusion, tyramine has low toxicity in rodents, has antioxidant effect, reduces plasma triglycerides and cholesterol levels. However, further studies should be conducted in rodents and non-rodents to better understand the pharmacodynamic and pharmacokinetic properties of tyramine.

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New potential biomarkers of acetaminophen-induced hepatotoxicity

Cited by 12 publications

References 45 publications

Biochemical and molecular study on the beneficial effect of Solubilized coenzyme Q10 on thioacetamide-induced liver fibrosis in adult male rats

Biochemical and molecular study on the beneficial effect of Solubilized coenzyme Q10 on thioacetamide-induced liver fibrosis in adult male rats

Rosemary (Rosmarinus officinalis L.) Glycolic Extract Protects Liver Mitochondria from Oxidative Damage and Prevents Acetaminophen-Induced Hepatotoxicity

Tyramine exerts hypolipidemic and anti-obesity effects in vivo

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