Sirtuin 1 Modulation in Rat Model of Acetaminophen-Induced Hepatotoxicity

Wojnarová, L; Canová, Nikolina Kutinová; Farghali, Hassan; Kučera, Tomáš

doi:10.33549/physiolres.933205

Cited by 30 publications

(20 citation statements)

References 33 publications

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“…In addition, we have provided new mechanistic insights to the recent work of Wojnarova et al (57) who reported decreased SIRT1 activity in rats treated with APAP that was reversed by resveratrol or the SIRT1 activator CAY10591. Wang et al (52) reported that resveratrol treatment was associated with elevated SIRT1 protein in mouse livers that were protected from APAP hepatotoxicity.…”

Section: Figmentioning

confidence: 65%

SIRT1 Controls Acetaminophen Hepatotoxicity by Modulating Inflammation and Oxidative Stress

Rada

Pardo

Mobasher

et al. 2018

Antioxidants & Redox Signaling

105

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SIRT1 protein levels are downregulated by IL1β/NFκB signaling in APAP hepatotoxicity, resulting in inflammation and oxidative stress. Thus, maintenance of SIRT1 during APAP overdose by inhibiting NFκB might be clinically relevant. Rebound Track: This work was rejected during standard peer review and rescued by Rebound Peer Review (Antioxid Redox Signal 16:293-296, 2012) with the following serving as open reviewers: Rafael de Cabo, Joaquim Ros, Kalervo Hiltunen, and Neil Kaplowitz. Antioxid. Redox Signal. 28, 1187-1208.

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Section: Figmentioning

confidence: 65%

SIRT1 Controls Acetaminophen Hepatotoxicity by Modulating Inflammation and Oxidative Stress

Rada

Pardo

Mobasher

et al. 2018

Antioxidants & Redox Signaling

105

View full text Add to dashboard Cite

show abstract

“…In addition, treatment with a SIRT1 activator has been shown to have no effect on early injury (6 hours) after APAP but decreases late injury (24 hours), while enhancing mitochondrial biogenesis and liver regeneration. Furthermore, resveratrol, which activates SIRT1, protected against APAP liver injury (76,77). Taken together, conflicting evidence exists regarding the role of SIRT1 in acute injury models.…”

Section: Discussionmentioning

confidence: 99%

Expression of mitochondrial membrane–linked SAB determines severity of sex-dependent acute liver injury

Win¹,

Min²,

Chen³

et al. 2019

Journal of Clinical Investigation

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Figure 3. SAB expression in male mice determines the susceptibility to APAP-induced liver injury in a JNK-dependent fashion. WT C57BL/6N male mice received Ad-lacZ or Ad-SAB. (A) Fourteen days later, SAB expression was analyzed by immunoblotting, and (B) APAP (150 mg/kg) was given i.p., and H&E staining was performed and serum ALT levels were determined after 24 hours. Original magnification, ×10. Scale bars: 100 μm. n = 3/group. ALT: *P < 0.05 versus Ad-lacZ-injected Sab iΔHep mice, by unpaired, 2-tailed Student's t test. Data are presented as the mean ± SD. (C) Sab fl/fl or Sab iΔHep mice received 0.05 5 × 10 9 to approximately 5 × 10 9 IU Ad-lacZ or Ad-SAB. Fourteen days later, SAB expression was determined by immunoblotting. Immunoblot is representative of 3 separate experiments. n = 3/group. *P < 0.05 versus Sab iΔHep + Ad-lacZ, by 1-way ANOVA with Bonferroni's correction. Data are presented as the mean ± SEM. (D) Mice received APAP (300 mg/kg, i.p.), and 24 hours later, liver sections were stained with H&E, and the necrotic area (percentage) was measured. Serum ALT (± SEM) (U/L) was measured. Scale bars: 100 μm. n = 3 mice/group. ALT: *P < 0.05, versus Ad-lacZ-injected Sab fl/fl mice; **P < 0.05, versus Ad-lacZ-injected Sab iΔHep mice, by unpaired, 2-tailed Student's t test. Data are presented as the mean ± SD. (E and F) Jnk1/2 fl/fl mice received AAV8-TBG-GFP (n = 3), AAV8-TBG-Cre (n = 5), or AAV8-TBG-Cre plus Ad-SAB (n = 3). Fourteen days later, JNK and SAB expression levels were determined by immunoblotting, or mice were treated with APAP to analyze liver injury and serum ALT levels. Scale bars: 100 μm. ALT: *P < 0.05, versus AAV8-TBG-GFP, by unpaired, 2-tailed Student's t test. Data are presented as the mean ± SD.

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“…The mean diameter of Glomeruli's space was measured in all groups of rats on day 8 and the relationship between Glomeruli's space and TNF-α, IL-6, MDA, and SOD are shown in (A -D), respectively. in rats have been reported (Wojnarová et al, 2015;Elbe et al, 2018). A recently published work (Elbe et al) reported a significant inhibition of liver iNOS immunostaining and hepatocyte ultrastructure damage by RES (10 mg/kg) given 20 minutes post APAP (1 g/kg) injection in rats.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Paracetamol-Induced Acute Kidney Damage in Rats Using a Combination of Resveratrol and Quercetin

et al. 2019

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Paracetamol (also called acetaminophen, or APAP) overdose causes acute damage to the liver and kidneys in both humans and experimental animal models via the induction of the oxidative stress pathway. We sought to determine whether the combined antioxidants and anti-inflammatory compounds, resveratrol (RES) and quercetin (QUR) can protect against kidney injury induced by a toxic dose of APAP in a rat model of APAP-induced acute kidney injury. Rats were either received a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pre-treated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. Harvested kidney tissues were prepared for light microscopy staining, and tissue samples were assayed for (i) biomarkers of oxidative stress and antioxidant, malondialdehyde (MDA) and superoxide dismutase (SOD); and (ii) biomarkers of inflammation, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Hematoxylin and eosin (H&E) stained images showed that APAP overdose induced acute kidney injury as demonstrated by widening of glomeruli space (Bowman space), tubular dilatation, numerous cellular debris in the renal tubules with tubular epithelial degeneration, and vacuolization, which were effectively protected by RES+QUR except a partial protection of the glomeruli space was observed. In addition, APAP significantly (p<0.05) modulated tissue levels of MDA, SOD, TNF-α, and IL-6, which were protected by RES+QUR. Furthermore, a significant (p<0.0001) positive correlation was observed between glomeruli space and TNF-α, (r=0.8899), IL-6 (r=0.8986), and MDA (r=0.8552), whereas glomeruli space scoring versus SOD showed negative correlation (r=-0.7870). We conclude that resveratrol plus quercetin substantially protects against APAP-induced acute kidney injury in rats, possibly via the augmentation of antioxidants and inhibition of oxidative stress and inflammation.

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Sirtuin 1 Modulation in Rat Model of Acetaminophen-Induced Hepatotoxicity

Cited by 30 publications

References 33 publications

SIRT1 Controls Acetaminophen Hepatotoxicity by Modulating Inflammation and Oxidative Stress

SIRT1 Controls Acetaminophen Hepatotoxicity by Modulating Inflammation and Oxidative Stress

Expression of mitochondrial membrane–linked SAB determines severity of sex-dependent acute liver injury

Inhibition of Paracetamol-Induced Acute Kidney Damage in Rats Using a Combination of Resveratrol and Quercetin

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