Taurine ameliorates thioacetamide induced liver fibrosis in rats via modulation of toll like receptor 4/nuclear factor kappa B signaling pathway.
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ABSTRACT:
SUBMITTER: Younis NS
PROVIDER: S-EPMC8192756 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Liver fibrosis is a complex inflammatory and fibrogenic process, and the progression of fibrosis leads to cirrhosis. The only therapeutic approaches are the removal of injurious stimuli and liver transplantation. Therefore, the development of anti-fibrotic therapies is desired. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide belonging to the N-acylethanolamines family and contained in foods such as egg yolks and peanuts. PEA has therapeutic anti-inflammatory, analgesic, and neuroprotective effects. However, the effects and roles of PEA in liver fibrosis remain unknown. Here we investigated the therapeutic effects of PEA in rats with liver fibrosis. Methods: We conducted in vitro experiments to investigate the effects of PEA on the activation of hepatic stellate cells (HSCs, LX-2). Liver fibrosis was induced by an intraperitoneal injection of 1.5 mL/kg of 50% carbon tetrachloride twice a week for 4 weeks. Beginning at 3 weeks, PEA (20 mg/kg) was intraperitoneally injected thrice a week for 2 weeks. Then rats were sacrificed and we performed histological and quantitative reverse-transcription polymerase chain reaction analyses. Results: The expression of α-smooth muscle actin (SMA) induced by transforming growth factor (TGF)-β1 in HSCs was significantly downregulated by PEA. PEA treatment inhibited the TGF-β1-induced phosphorylation of SMAD2 in a dose-dependent manner, and upregulated the expression of SMAD7. The reporter gene assay demonstrated that PEA downregulated the transcriptional activity of the SMAD complex upregulated by TGF-β1. Administration of PEA significantly reduced the fibrotic area, deposition of type I collagen, and activation of HSCs and Kupffer cells in rats with liver fibrosis. Conclusion: Activation of HSCs was significantly decreased by PEA through suppression of the TGF-β1/SMAD signaling pathway. Administration of PEA produced significant improvement in a rat model of liver fibrosis, possibly by inhibiting the activation of HSCs and Kupffer cells. PEA may be a potential new treatment for liver fibrosis.
| S-EPMC6053486 | biostudies-literature
Project description:The aim is to characterize rat liver fibrosis induced by thioacetamide (TAA). To induce hepatic fibrosis, Male Sprague Dawley rats (9-12 weeks of age and 380-420 g of weight upon arrival, supplied by Beijing Vital River laboratory animal Co., Ltd.) were treated with thioacetamide (TAA). Rat liver samples were collected from five groups of rats at week 1, 2, 4, 8 and 13 after TAA (300 mg/kg) administration three times per week while five control groups receive the same volume of 0.9% normal saline. Four biological replicates were used for each group.
2021-09-29 | E-MTAB-10547 | biostudies-arrayexpress
Project description:Certain bioactive peptides are reported to be able to alleviate hepatic fibrosis. Our previous work has confirmed the hepatoprotective effect of corn peptides (CPs) that are prepared from a high protein by-product, corn gluten meal, on acute liver injury in an animal model. However, the antifibrotic activity of CPs remained to be elucidated. In this study, the hepatoprotective effect of CPs on thioacetamide (TAA)-induced liver fibrosis was tested. Results showed that CPs (100 mg/kg body weight) significantly decreased the levels of alanine transaminase/aspartate transaminase, laminin, type IV collagen, and type III collagen in serum and increased the serum albumin levels and total antioxidant capacity. Additionally, with CP treatment (100 mg/kg body weight), a significant decrease was observed in the levels of malondialdehyde, nitric oxide, hydroxyproline, transforming growth factor ?1, and lactate dehydrogenase activity as well as the liver index, while the activity of superoxidedismutase was significantly increased in livers. The histological and morphological analysis showed that the hepatocyte structure in CP-treated rats was superior to that of TAA-injured rats, and inflammation and fibrosis were also ameliorated. Therefore, CPs can be used as an option for prevention and adjuvant therapy of liver fibrosis.
| S-EPMC3806372 | biostudies-literature
Project description:Several hepatic pathological conditions are correlated with the stimulation of hepatic stellate cells. This induces a cascade of events producing accretion of extracellular matrix components triggering fibrosis. Dunaliella salina, rich in carotenoids, was investigated for its potential antagonizing activity; functionally and structurally against thioacetamide (TAA) - induced hepatic fibrosis in rats. Adult male albino Wistar rats were treated with three dose levels of D. salina powder or extract (daily, p.o.); for 6 weeks, concomitantly with TAA injection. Serum levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin and albumin were determined. Reduced glutathione (GSH), malondialdehyde (MDA), smooth muscle actin alpha (α-SMA) and collagen I hepatic contents were also estimated. Treatment with D. salina powder or extract caused a significant decline in serum levels of AST, ALT, ALP, bilirubin, MDA and hepatic contents of α-SMA and collagen I. Additionally, serum albumin and GSH hepatic content were highly elevated. Liver histopathological examination also indicated that D. salina reduced fibrosis, centrilobular necrosis, and inflammatory cell infiltration evoked by TAA. The results implied that D. salina exerts protective action against TAA-induced hepatic fibrosis in rats. The phytochemical investigation revealed high total carotenoid content prominently β-carotene (15.2 % of the algal extract) as well as unsaturated fatty acids as alpha-linolenic acid which accounts for the hepatoprotective activity.
| S-EPMC6920116 | biostudies-literature
Project description:ObjectivesEven after the glucose level returns to normal, hyperglycemia-induced cardiac dysfunction as well as reactive oxygen species (ROS) generation, inflammatory responses, and apoptosis continued deterioration, showing a long-lasting adverse effect on cardiac function and structure. We aimed to unveil the molecular and cellular mechanisms underlying hyperglycemia-induced persistent myocardial injury and cardiac dysfunction.Methods and resultsRecently, the accumulated evidence indicated epigenetic regulation act as a determining factor in hyperglycemia-induced continuous cardiovascular dysfunction. As an important histone demethylase, the expression of lysine-specific demethylase 3A (KDM3A) was continually increased, accompanied by a sustained decline of H3K9me2 levels in diabetic myocardium even if received hypoglycemic therapy. Besides, by utilizing gain- and loss-of-functional approaches, we identified KDM3A as a novel regulator that accelerates hyperglycemia-mediated myocardial injury by promoting ROS generation, aggregating inflammatory reaction, and facilitating cell apoptosis in vitro and in vivo. The KDM3A inhibition could significantly ameliorate the adverse effect of hyperglycemia in both diabetes model and diabetic intensive glycemic control model. Mechanically, our data uncovered that KDM3A could promote the expression and transcriptional activity of nuclear factor kappa-B (NF-κB/P65), and the succedent rescue experiments further verified that KDM3A regulates hyperglycemia-induced myocardial injury in an NF-κB/P65 dependent manner.ConclusionThis study revealed histone-modifying enzymes KDM3A drives persistent oxidative stress, inflammation, apoptosis, and subsequent myocardial injury in the diabetic heart by regulating the transcription of NF-κB/P65.
| S-EPMC9106140 | biostudies-literature
Project description:Acute liver failure (ALF) is a life-threatening disorder of liver function. Kynurenic acid (KYNA), a tryptophan metabolite formed along the kynurenine metabolic pathway, possesses anti-inflammatory and antioxidant properties. Its presence in food and its potential role in the digestive system was recently reported. The aim of this study was to define the effect of KYNA on liver failure. The Wistar rat model of thioacetamide-induced liver injury was used. Morphological and biochemical analyses as well as the measurement of KYNA content in liver and hepatoprotective herbal remedies were conducted. The significant attenuation of morphological disturbances and aspartate and alanine transaminase activities, decrease of myeloperoxidase and tumor necrosis factor-?, and elevation of interleukin-10 levels indicating the protective effect of KYNA in thioacetamide (TAA) - induced liver injury were discovered. In conclusion, the hepatoprotective role of KYNA in an animal model of liver failure was documented and the use of KYNA in the treatment of ALF was suggested.
| S-EPMC6171262 | biostudies-literature
Project description:This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control) or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis) three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg) or ELAP (250 or 500 mg/kg). Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed to result from the reduction of thioacetamide-induced toxicity, normalizing reactive oxygen species levels, inhibiting cellular proliferation, and inducing apoptosis in HepG2 cells.
| S-EPMC4184875 | biostudies-literature
Project description:Drug-induced liver fibrosis models are used in normal and immunosuppressed small animals for transplantation and regenerative medicine to improve liver fibrosis. Although large animal models are needed for pre-clinical studies, they are yet to be established owing to drug sensitivity in animal species and difficulty in setting doses. In this study, we evaluated liver fibrosis by administering thioacetamide (TA) to normal microminipig and thymectomized microminipig; 3 times for 1 week (total duration: 8 weeks). The pigs treated with TA showed elevated blood cytokine levels and a continuous liver injury at 8 weeks. RNA-seq of the liver showed increased expression of fibrosis-related genes after TA treatment. Histopathological examination showed degenerative necrosis of hepatocytes around the central vein, and revealed fibrogenesis and hepatocyte proliferation. TA treatment caused CD3-positive T cells and macrophages scattered within the hepatic lobule to congregate near the center of the lobule and increased αSMA-positive cells. Thymectomized pigs showed liver fibrosis similar to that of normal pigs, although the clinical signs tended to be milder. This model is similar to pathogenesis of liver fibrosis reported in other animal models. Therefore, it is expected to contribute to research as a drug discovery and pre-clinical transplantation models.
| S-EPMC10495379 | biostudies-literature
Project description:This study aimed at investigating the chemical composition and the hepatoprotective activities of Plumbago indica L. and P. auriculata Lam. LC-MS/MS analyses for the hydroalcoholic extracts of the aerial parts of the two Plumbago species allowed the tentative identification of thirty and twenty-five compounds from P. indica and P. auriculata, respectively. The biochemical and histopathological alterations associated with thioacetamide (TAA)-induced liver fibrosis in rats were evaluated in vivo where rats received the two extracts at three different dose levels (100, 200 and 400 mg/kg p.o, daily) for 15 consecutive days with induction of hepatotoxicity by TAA (200 mg/kg/day, i.p.) at 14th and 15th days. Results of the present study showed a significant restoration in liver function biomarkers viz. alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamyl transferase and total bilirubin. The liver homogenates exhibited increased levels of antioxidant biomarkers: reduced glutathione (GSH) and catalase (CAT), accompanied with decline in malondialdehyde (MDA). Furthermore, treated groups exhibited a significant suppression in liver inflammatory cytokines: tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6), and fibrotic biomarker: alpha smooth muscle relaxant. Histopathological examination of the liver showed normality of hepatocytes. Noteworthy, P. indica extract showed better hepatoprotective activity than P. auriculata, particularly at 200 mg/kg. To sum up, all these results indicated the hepatoprotective properties of both extracts, as well as their antifibrotic effect was evidenced by reduction in hepatic collagen deposition. However, additional experiments are required to isolate their individual secondary metabolites, assess the toxicity of the extracts and explore the involved mechanism of action.
| S-EPMC9197831 | biostudies-literature
Project description:In schistosomiasis, egg-induced hepatic granuloma formation is a cytokine-mediated, predominantly CD4(+) Th2 immune response that can give rise to hepatic fibrosis. Hepatic fibrosis is the main cause of increased morbidity and mortality in humans with schistosome infection. Taurine has various physiological functions and hepatoprotective properties as well as anti-inflammatory and immunomodulatory activity. However, little is known about the role of taurine in schistosome egg-induced granuloma formation and fibrosis. We aimed to evaluate the therapeutic potential of taurine as preventative treatment for Schistosoma japonicum infection. Mice infected with S. japonicum cercariae were supplied with taurine drinking water (1% w/v) for 4 weeks starting at 4 weeks post-infection. Taurine supplementation significantly improved the liver pathologic findings, reduced the serum levels of aminotransferases and area of hepatic granuloma, and prevented fibrosis progression. In addition, taurine decreased the expression of the granulomatous and fibrogenic mediators transforming growth factor β1, tumor necrosis factor α, monocyte chemotactic protein 1α and macrophage inflammatory protein 1α as well as the endoplasmic reticulum stress marker glucose-regulated protein 78. Thus, taurine can significantly attenuate S. japonicum egg-induced hepatic granuloma and fibrosis, which may depend in part on the downregulation of some relevant cytokine/chemokines and reducing the endoplasmic reticulum stress response.
| S-EPMC4805782 | biostudies-literature