Cirrhosis induced by thioacetamide is prevented by stevia. Molecular mechanisms

Ramos‐Tovar, Erika; Casas‐Grajales, Sael; Hernández-Aquino, Erika; Flores-Beltrán, Rosa E.; Galindo-Gómez, Silvia; Vera-Aguilar, Eunice; Dı́az-Ruiz, Araceli; Montes, Sergio; Camacho, Javier; Tsutsumi, Vı́ctor; Muriel, Pablo

doi:10.1016/j.jff.2018.11.039

Cited by 11 publications

(3 citation statements)

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“…Several studies have been performed to investigate the effects of various antioxidants on different models of liver damage and have shown the causative role of ROS in the profibrogenic process. In models of bile duct ligation-, CCl 4 -, and thioacetamide chronic intoxication-induced fibrosis in rodents and in vitro studies, several compounds with direct or indirect antioxidant activity have been shown to prevent or reverse the accumulation of extracellular matrix (ECM) proteins (fibrotic tissue) within the hepatic parenchyma or the production of profibrogenic genes or proteins [ 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ]. One of the most studied phytodrugs with important antioxidant properties is silibinin, the main active constituent of silymarin [ 73 ].…”

Section: Role Of Free Radicals In Liver Fibrosismentioning

confidence: 99%

Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver

Ramos‐Tovar¹,

2020

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Activated hepatic stellate cells (HSCs) and myofibroblasts are the main producers of extracellular matrix (ECM) proteins that form the fibrotic tissue that leads to hepatic fibrosis. Reactive oxygen species (ROS) can directly activate HSCs or induce inflammation or programmed cell death, especially pyroptosis, in hepatocytes, which in turn activates HSCs and fibroblasts to produce ECM proteins. Therefore, antioxidants and the nuclear factor E2-related factor-2 signaling pathway play critical roles in modulating the profibrogenic response. The master proinflammatory factors nuclear factor-κB (NF-κB) and the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome may coordinate to produce and activate profibrogenic molecules such as interleukins 1β and 18, which effectively activate HSCs, to produce large amounts of fibrotic proteins. Furthermore, the NLRP3 inflammasome activates pro-caspase 1, which is upregulated by NF-κB, to produce caspase 1, which induces pyroptosis via gasdermin and the activation of HSCs. ROS play central roles in the activation of the NF-κB and NLRP3 signaling pathways via IκB (an inhibitor of NF-κB) and thioredoxin-interacting protein, respectively, thereby linking the molecular mechanisms of oxidative stress, inflammation and fibrosis. Elucidating these molecular pathways may pave the way for the development of therapeutic tools to interfere with specific targets.

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Section: Role Of Free Radicals In Liver Fibrosismentioning

confidence: 99%

Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver

Ramos‐Tovar¹,

2020

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“…The metabolism of TAA involved the formation of a thiono-sulfur compound, which induce hepatic damage and fibrosis might responsible for these biochemical changes (Hajovsky et al, 2012;mousa et al, 2019;Zargar, 2014) Grossly, the liver of TAA-treated rats showed multifocal to coalescing micro-nodules on hepatic surfaces. This lesion was commonly reported as a characteristic finding in liver cirrhosis (Amin et al, 2012;Hwang et al, 2012;Ramos-Tovar et al, 2019). Microscopically, there is disruption of the hepatic parenchyma with marked portal fibrosis, which was observed as early as 6 weeks post-TAA treatment.…”

Section: Discussionmentioning

confidence: 78%

Sequential proliferative lesions in the cirrhotic liver of rats: a histopathological and immunohistochemical study

Darweish¹,

GabAllh²,

El-Mashad³

et al. 2021

Kafrelsheikh Veterinary Medical Journal

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Background/aim: Liver cirrhosis is a common health problem that is mostly at the late stage associated with hepatic carcinogenesis. This study aimed to clarify the sequential proliferative lesions in the cirrhotic liver induced chemically by thioacetamide (TAA) in rats. Methods: Thirty male albino rats were equally divided into control and TAA groups. In the TAA group, rats were intraperitoneally injected with 100 mg/kg TAA twice /week for 18 weeks. Animals were euthanized after 6, 12, and 18 weeks. Blood and liver samples were collected for biochemical analysis and histopathological examination. Results: TAA-treated group had significantly increased serum levels of liver damage parameters (alanine transaminase, aspartate transaminase, and alkaline phosphatase), and hepatic levels of oxidative stress-related markers (malondialdehyde and nitric oxide) as compared to the control group. Meanwhile, the TAA group showed significantly decreased hepatic levels of antioxidant markers (reduced glutathione and superoxide dismutase) relative to the control group. Histopathological examination of the liver revealed characteristic lesions of liver cirrhosis in form of regenerative nodules, the proliferation of bile ducts epithelium and hepatic stellate cells as well as different types of foci of cellular alterations which were prominent proliferative lesions in the liver of the TAA group. However, with TAA prolonged treatment, cellular atypia and preneoplastic changes became evident in many hepatocytes. Immunohistochemical expression for Ki67 revealed positive nuclear labeling in some hepatocytes of TAA-treated rats. Marked expression for Ki67 in regenerating nodules at 18 weeks following TAA treatment was interesting as it revealed a higher regeneration activity. Conclusion: Some proliferative lesions such as regenerative nodules and foci of cellular alteration in hepatic cirrhosis may later constitute carcinogenic development.

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“…Administration of TAA induces oxidative stress in liver tissue via the generation of hydroperoxides during membrane lipid peroxidation, which is reflected in the decrease of hepatic GSH concentrations ( Figure 5 ) as well as the increase in the MDA values ( Figure 6 ) [ 62 ] and the activity of glutathione peroxidase [ 63 ]. The toxic metabolite of TAA (TASO 2 ) acts as an electrophilic compound that increases cellular oxidative stress.…”

Section: Resultsmentioning

confidence: 99%

Hepatoprotective Effect of Opuntia robusta Fruit Biocomponents in a Rat Model of Thioacetamide-Induced Liver Fibrosis

Pulido-Hornedo

Ventura-Juárez

Guevara‐Lara

et al. 2022

Plants

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Liver fibrosis is a chronic disease associated with oxidative stress that has a great impact on the population mortality. Due to their antioxidant capacity, we evaluated the protective effect of Opuntia robusta fruit (Or) on liver fibrosis. A nutraceutical characterization of Or was performed and a model of fibrosis was induced with thioacetamide (TAA) in Wistar rats. Aminotransferases, reduced glutathione (GSH) and histopathology were evaluated. Or contained 436.5 ± 57 mg of Betacyanins equivalents/L., 793 mg of catechin equivalents (CAE)/100 g for flavonoids, 1118 mg of gallic acid equivalents (GAE)/100 g for total phenols, 141.14 mg/100 g for vitamin C and 429.9 μg/100 g for vitamin E. The antioxidant capacity of Or was: 2.27 mmol of Trolox® equivalents (TE)/L (DPPH), 62.2 ± 5.0 μmol TE/g (ABTS•+), 80.2 ± 11.7 μmol TE/g (FRAP), 247.9 ± 15.6 µmol TE/g (AAPH) and 15.0% of H2O2 elimination. An increase (p < 0.05) of aminotransferases and a decrease (p < 0.05) of hepatic GSH was observed in the TAA group compared to the control and the concomitant groups. Histopathology showed changes in the normal architecture of the liver treated with TAA compared to the concomitant treatments. Or contains bioactive components with antioxidant capacity, which can reduce fibrotic liver damage.

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Cirrhosis induced by thioacetamide is prevented by stevia. Molecular mechanisms

Cited by 11 publications

References 57 publications

Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver

Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver

Sequential proliferative lesions in the cirrhotic liver of rats: a histopathological and immunohistochemical study

Hepatoprotective Effect of Opuntia robusta Fruit Biocomponents in a Rat Model of Thioacetamide-Induced Liver Fibrosis

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