Antioxidant protection by β‐selenoamines against thioacetamide‐induced oxidative stress and hepatotoxicity in mice

Stefanello, Sílvio Terra; Hartmann, Diane Duarte; Amaral, Guilherme Pires; Courtes, Aline Alves; Leite, Martim T.B.; Silva, Thayanara Cruz da; Gonçalves, Débora Farina; Souza, Micaela B.; Rosa, Pâmela Carvalho da; Dornelles, Luciano; Soares, Félix Alexandre Antunes

doi:10.1002/jbt.21974

Cited by 6 publications

(3 citation statements)

References 41 publications

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“…In the present investigation, TAA was used to induce hepatotoxicity in the rat experimental model. [26,27] It has been reported that TAA successfully induces an experimental rat model of hepatic fibrosis when dosed with 200 mg/kg, intraperitoneally (IP) twice a week for 6 consecutive weeks. [28,29] We have used DMF as an intervention agent, and the dose was selected considering that at least two doses should fall in the dose range used in clinics.…”

Section: The Rationality Of Dose Selectionmentioning

confidence: 99%

Dimethyl fumarate protects thioacetamide‐induced liver damage in rats: Studies on Nrf2, NLRP3, and NF‐κB

Dwivedi

Jena

Kumar

2020

J Biochem & Molecular Tox

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The present study was designed to investigate the hepatoprotective potential of dimethyl fumarate (DMF) against thioacetamide (TAA)‐induced liver damage. Wistar rats were treated with DMF (12.5, 25, and 50 mg/kg/day, orally) and TAA (200 mg/kg intraperitoneally, every third day) for 6 consecutive weeks. TAA exposure significantly reduced body weight, increased liver weight and index, and intervention with DMF did not ameliorate these parameters. DMF treatment significantly restored TAA‐induced increase in the levels of aspartate aminotransferase, alanine aminotransferase, γ‐glutamyl transferase, total bilirubin, uric acid, malondialdehyde, reduced glutathione, and histopathological findings such as inflammatory cell infiltration, deposition of collagen, necrosis, and bridging fibrosis. DMF treatment significantly ameliorated TAA‐induced hepatic stellate cell activation, increase in inflammatory cascade markers (NACHT, LRR, and PYD domains‐containing protein 3; NLRP3, apoptosis‐associated speck like protein containing a caspase recruitment domain; ASC, caspase‐1, nuclear factor‐kappa B; NF‐κB, interleukin‐6), fibrogenic makers (α‐smooth muscle actin; ɑ‐SMA, transforming growth factor; TGF‐β1, fibronectin, collagen 1) and antioxidant markers (nuclear factor (erythroid‐derived 2)‐like factor 2; Nrf2, superoxide dismutase‐1; SOD‐1, catalase). The present findings concluded that DMF protects against TAA‐induced hepatic damage mediated through the downregulation of inflammatory cascades and upregulation of antioxidant status.

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Section: The Rationality Of Dose Selectionmentioning

confidence: 99%

Dimethyl fumarate protects thioacetamide‐induced liver damage in rats: Studies on Nrf2, NLRP3, and NF‐κB

Dwivedi

Jena

Kumar

2020

J Biochem & Molecular Tox

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“…14,23 TASO and TASO 2 are ultimate hepatotoxicants and cause centrilobular necrosis of hepatocytes by covalent binding to proteins and lipids 19,23,33,60 and/or induction of oxidative stress such as lipid peroxidation. 30,55,56,57 Oxidative stress such as generation of hydroxyl radicals and other electrophilic molecules can cause DNA damage including double-strand breaks. 16,38 In the TAA model, dietary iron overload enhances TAA-induced hepatocellular injury with increased DNA damage and hepatic MDA content.…”

Section: Resultsmentioning

confidence: 99%

Difference in the Mechanism of Iron Overload–Enhanced Acute Hepatotoxicity Induced by Thioacetamide and Carbon Tetrachloride in Rats

Inai,

Izawa,

Kamei

et al. 2024

Toxicol Pathol

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Iron overload has been recognized as a risk factor for liver disease; however, little is known about its pathological role in the modification of liver injury. The purpose of this study is to investigate the influence of iron overload on liver injury induced by two hepatotoxicants with different pathogenesis in rats. Rats were fed a control (Cont), 0.8% high-iron (0.8% Fe), or 1% high-iron diet (1% Fe) for 4 weeks and were then administered with saline, thioacetamide (TAA), or carbon tetrachloride (CCl4). Hepatic and systemic iron overload were seen in the 0.8% and 1% Fe groups. Twenty-four hours after administration, hepatocellular necrosis induced by TAA and hepatocellular necrosis, degeneration, and vacuolation induced by CCl4, as well as serum transaminase values, were exacerbated in the 0.8% and 1% Fe groups compared to the Cont group. On the other hand, microvesicular vacuolation induced by CCl4 was decreased in 0.8% and 1% Fe groups. Hepatocellular DNA damage was increased by iron overload in both models, whereas a synergistic effect of oxidative stress by excess iron and hepatotoxicant was only present in the CCl4 model. The data showed that dietary iron overload exacerbates TAA- and CCl4-induced acute liver injury with different mechanisms.

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“…Acute hepatic and kidney injury was induced by a single 200 mg/kg TAA intraperitoneal injection as previously described [ 29 ]. Mice (n = 30) were randomly divided into five sets (6 mice/group): The control (CTRL) group, where mice received normal saline; the OA group that was treated with OA (90 mg/kg/day for 7 days); the TAA group, where mice were injected with TAA; the OA 45 + TAA and OA 90 + TAA groups, where mice received OA at 45 and 90 mg/kg, respectively, for 7 days before TAA challenge.…”

Section: Methodsmentioning

confidence: 99%

SIRT1/Nrf2/NF-κB Signaling Mediates Anti-Inflammatory and Anti-Apoptotic Activities of Oleanolic Acid in a Mouse Model of Acute Hepatorenal Damage

Alqrad,

El-Agamy,

Ibrahim

et al. 2023

Medicina

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Background and objectives: Oleanolic acid (OA) is a penta-cyclic triterpene with diverse bioactivities such as anticarcinogenic, antiviral, antimicrobial, hepatoprotective, anti-atherosclerotic, hypolipidemic, and gastroprotective. However, its effects on hepatorenal damage remain unclear. The protective activity of OA, separated from Viscum schimperi (Loranthaceae), against TAA (thioacetamide)-produced acute hepatic and renal damage was explored. Materials and Methods: Mice were treated with OA for 7 days before TAA (200 mg/kg, i.p.). Serum indices of hepatorenal injury, pathological lesions, molecular biological indexes, and inflammatory/apoptotic genes were estimated. Results: The tissues of both organs were greatly affected by the TAA injection. That was evident through increased serum markers of hepato-renal injury as well as remarkable histopathological lesions. TAA-induced injury was associated with oxidative and inflammatory responses in both organs as there was an elevation of oxidative stress parameters (4-HNE (4-hydroxy-nonenal), MDA (malondialdehyde), NOx (nitric oxide)), decline of antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (TAC)), and an increase in the gene expression/level of inflammatory mediators (interleukins (1β&6)). The inflammatory response was linked to a significant activation of NF-κB (nuclear-factor kappa-B)/TNF-α (tumor-necrosis factor-alpha) signaling. The inflammatory response in both organs was accompanied by apoptotic changes, including a rise in the gene expression and level of apoptotic parameters (caspase-3 and Bax) along with a decline in Bcl-2 (anti-apoptotic parameter) gene expression and level. These pathogenic events were found to be closely related to the suppression of the antioxidant signaling pathway, Nrf2 (nuclear-factor erythroid 2–related factor-2)/SIRT1 (sirtuin-1)/HO-1 (heme-oxygenase 1). On the other hand, OA significantly ameliorated TAA-induced injury in both organs. On the other hand, OA counterpoised the inflammatory response as it ameliorated NF-κB/TNF-α signaling and cytokine release. OA enhanced Nrf2/SIRT1/HO-1 signaling and counteracted apoptotic damage. Conclusions: OA showed anti-inflammation and antiapoptotic capacities that effectively suppressed TAA-induced acute hepatorenal damage.

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Antioxidant protection by β‐selenoamines against thioacetamide‐induced oxidative stress and hepatotoxicity in mice

Cited by 6 publications

References 41 publications

Dimethyl fumarate protects thioacetamide‐induced liver damage in rats: Studies on Nrf2, NLRP3, and NF‐κB

Dimethyl fumarate protects thioacetamide‐induced liver damage in rats: Studies on Nrf2, NLRP3, and NF‐κB

Difference in the Mechanism of Iron Overload–Enhanced Acute Hepatotoxicity Induced by Thioacetamide and Carbon Tetrachloride in Rats

SIRT1/Nrf2/NF-κB Signaling Mediates Anti-Inflammatory and Anti-Apoptotic Activities of Oleanolic Acid in a Mouse Model of Acute Hepatorenal Damage

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