Thioacetamide Research Articles

Protective Role of Quercetin on Thioacetamide-Induced Renal Injury in Adult Male Albino Rats

Background: Thioacetamide (TAA) is a recognized industrial poisonous agent drastically used in animal studies for induction of hepatic necrosis, fibrosis and cirrhosis. It is additionally reported to be nephrotoxic through induction of oxidative stress. Quercetin (QE) has a high antioxidant capacity via free radical scavenging, transition metal ion binding, and lipid peroxidation inhibition. Aim of the work: The goal of this research was to see if QE may help reduce the negative effects of thioacetamide on renal tissue by histological examination of the kidney. Material and methods: Twenty four adult male Albino rats 7–9 weeks old around 180–200g body weight were allocated into 3 groups; Group I (n=8) receiving distilled water, Group II (n=8); rats receiving TAA and Group III (n=8); receiving TAA and QE. Results: Renal tissues were examined under a light microscope stained by Harris Hematoxylin & Eosin (H&E stain), Periodiceeacid Schiff (PAS) andjMasson’srTrichrome for TAA-treated groups revealed severe histopathological changes, whereas specimens obtained from QE-treated groups showed onlywmild changes. Immunohistochemical results corroborated these findings. Conclusion: This study demonstrated the ameliorative consequences of QE in opposition to TAA-induced renal injury in rats. The result of this study might contribute in the development of a novel complementary alternative medication in combating and therapeutic intervention of TAA-induced renal injury. KEY WORDS: Thioacetamide, renal, quercetin, albino rat and histopathology.

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Luteolin is a flavone that serves as a natural antioxidant. The therapeutic impacts of luteolin is influenced by its antioxidant, anti-inflammatory, anticancer, neuroprotective and antineoplastic properties. This study aimed to establish an animal model of testicular toxicity caused by Thioacetamide (TAA). In addition, high doses of Luteolin (LUT) were supplemented to observe the role of LUT in attenuating spermato-toxicity, the hazard of oxidative stress, and testicular histopathological alterations induced by TAA. Thirty adult rats were equally divided into three groups as follow; G1: negative control group, G2: was given TAA 200 mg/kg body weight, G3: was received LUT at a dose of (50 mg/kg body weight) for four weeks concurrently with TAA. During this experiment histological, immunohistochemical, biochemical and morphometric measures were evaluated. TAA revealed loss of normal architecture of testicular tissue, wide interstitial spaces, and a loss of stratal arrangement of germinal epithelium with intercellular spacing. Also, a reduction in the number of +ve vimentin staining Sertoli cells with a marked reduction in the mean of vimentin-positive cells increased oxidative stress in testicular tissue. LUT protected testis against these alterations. By reducing oxidative stress, histological and immunohistochemical alterations and restoring the normal testicular tissue architecture and function, LUT successfully lowers TAA testicular toxicity in albino rats, recommending that it may have similar effects in humans. © 2022 Friends Science Publishers

Development of an experimental hepatic encephalopathy in a rabbit model: Biochemical and immunohistochemical study

This study was designed to estimate the biochemical, histochemical, and immunohistochemical aspects of hepatic encephalopathy (HE) induced experimentally by using Thioacetamide (TAA). Twenty-four male rabbits were separated into four main groups (6 each), the Control group (group I) and Group II; rabbits were injected with TAA dissolved in distal water at 200 mg/kg B.W. twice weekly for eight weeks. Group III was given silymarin orally dissolved in saline 200mg/kg B.W. daily for eight weeks. Group IV animals received TAA and Silymarin 200 mg/kg B.W. for eight weeks. The results revealed animals treated with TAA indicated a significant decrease in the level of TSP and a significant increase in the levels of TSB, ALP, ALT, and AST. Histopathological examination of each liver and brain indicates necrosis of the hepatocytes, Cholangitis, biliary duct epithelium hyperplasia and preductular fibrosis, and collagen fiber deposition in the portal triad. Necrosis of the neurons, Purkinjean, and molecular cells with a decrease in granular cells and thickening of meninges. The histochemical examination of the liver revealed the presence of fibrosis in the portal area and the peri-lobular septa and the presence portal to portal bridging fibrosis. The immunohistochemical stain of the liver section revealed a positive reaction for collagen type IV, especially in/and around the portal tried as well as in the septa between the lobules. In conclusion, in the rabbit's model, hepatotoxicity to the early stages of the pathogenesis of hepatoencephalopathy.

Effects of chronic cirrhosis induced by intraperitoneal thioacetamide injection on the protein content and Michaelis-Menten kinetics of cytochrome P450 enzymes in the rat liver microsomes.

Chronic intraperitoneal injection of thioacetamide (TAA) in rats has been used as an animal model of human cirrhosis to study the effects of the disease on drug metabolism. However, TAA inhibits P450 enzymes directly and independently of cirrhosis. We investigated the effects of chronic cirrhosis in rats, induced by 10 weeks of intraperitoneal TAA, on the P450 enzymes after a 10-day washout period to eliminate TAA. Liver histology and serum biomarkers of hepatic function confirmed cirrhosis in all animals. Microsomal total P450 content, P450 reductase activity and ethoxycoumarin O-deethylase activity, a general marker of P450 activity, were significantly reduced by 30%-50% in cirrhotic animals. Additionally, the protein content and Michaelis-Menten kinetics of the activities of CYP2D, CYP2E1 and CYP3A were investigated. Whereas cirrhosis reduced the microsomal protein contents of CYP2D and CYP3A by 70% and 30%, respectively, the protein contents of CYP2E1 were not affected. However, the activities of all the tested isoenzymes were substantially lower in the cirrhotic livers. It is concluded that the TAA model of cirrhosis that incorporates a 10-day washout period after intraperitoneal injection of the chemical to rats produces isoenzyme-selective reductions in the P450 proteins or activities, which are independent of the direct inhibitory effects of TAA.

Flavonoid constituents and protective efficacy of Citrus reticulate (Blanco) leaves ethanolic extract on thioacetamide-induced liver injury rats

Context: Oxidative stress leads to deleterious processes in the liver that resulted in liver diseases. Objective: To evaluate antioxidant activity and hepatoprotective potential of ethanolic leaves extract of Citrus reticulate against hepatic dysfunction induced by thioacetamide (TAA). Materials and Methods: Flavonoid constituents were isolated from the ethanol extract by chromatographic techniques and identified by the spectroscopic analyses. Antioxidant activity was determined using DPPH assay. Hepatotoxicity was induced in rats via intraperitoneal injection of TAA and the ethanol extract was orally administrated at a dose of 100 mg/kg/day for four weeks. Serum biomarkers, hepatic antioxidant enzymes, tumour necrosis factor-alpha (TNF-α), hepatic hydroxyproline levels, and histopathology were examined. Results: Ten known flavonoids were identified, among of them, 6,3`-dimethoxyluteolin and 8,3`-dimethoxyluteolin possessed the highest antioxidant activity. The substantially elevated serum enzymatic levels of ALT, ALP, and bilirubin were found to be restored towards normalisation significantly by the plant extract. Furthermore, the markers including MDA, GSH, SOD, NO, and protein carbonyl which were close to oxidative damage, were restored. Meanwhile, the extract treatment decreased TNF-α level and also was able to reverse the induced fibrosis by significantly reducing the hydroxyproline content. Moreover, histopathological studies further substantiate the protective effect of the extract. Conclusion: C. reticulate leaves extract is a rich source of phytochemicals with in vitro and in vivo protective effects.

Hepatoprotective effect of pinostrobin against thioacetamide-induced liver cirrhosis in rats

The study in vivo assessed the effect of pinostrobin on the histology, immunohistochemistry, and biochemical parameters of thioacetamide (TAA) induced liver cirrhosis in Sprague Dawley rats. The rats were noticeably gavaged with two doses of pinostrobin (30 mg/kg and 60 mg/kg) with TAA and exhibited a substantial decrease in the liver index and hepatocyte propagation with much minor cell injury. These groups meaningfully down-regulated the proliferation of cellular nucleus antigen (PCNA) and alpha-smooth muscle actin (α-SMA). The liver homogenate displayed augmented antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) activities escorted with reducing in malondialdehyde (MDA) level. The serum level of bilirubin, total protein, albumin, and liver enzymes (ALP, ALT, and AST) returned to normal and was similar to that of normal control and silymarin with TAA-treated groups. pinostrobin-fed groups also decreased the level of Tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and increased the level of Interleukin-10 (IL-10). Acute toxicity with a higher dose of 500 mg/kg of pinostrobin did not manifest any toxicological signs in rats. The hepatoprotective effect of pinostrobin could be due to potentially inhibited the progression of liver cirrhosis, down-regulation of PCNA and α-SMA proliferation, prevented oxidation of hepatocytes, improved SOD and CAT enzymes, condensed MDA, repairs of liver biomarkers, reduced cellular inflammation and modulation of inflammatory cytokines.

Model of Liver Fibrosis Induction by Thioacetamide in Rats for Regenerative Therapy Studies.

Hepatic fibrosis is caused by chronic injury due to toxic, infectious, or metabolic causes, and it may progress to cirrhosis and hepatocellular carcinoma. There is currently no antifibrotic therapy authorized for human use; however, there are promising studies using cell therapies. There are also no animal models that exactly reproduce human liver fibrosis that can be used to better understand the mechanisms of its regression and identify new targets for treatment and therapeutic approaches. On the other hand, mesenchymal stem cells (MSC) have experimentally demonstrated fibrosis regression effects, but it is necessary to have an animal model of advanced liver fibrosis to evaluate the effect of these cells. The aim of this work was to establish a protocol for the induction of advanced liver fibrosis in rats using thioacetamide (TAA), which will allow us to perform trials using MSC as a possible therapy for fibrosis regression. For this purpose, we selected 24 female rats and grouped them into three experimental groups: the control group (G-I) without treatment and groups II (G-II) and III (G-III) that received TAA by intraperitoneal injection for 24 weeks. Then, 1 × 106/kg adipose mesenchymal stem cells (ASCs) were infused intravenously. Groups G-I and G-II were sacrificed 7 days after the last dose of ASC, and G-III was sacrificed 8 weeks after the last ASC infusion, all with xylazine/ketamine (40 mg/kg). The protocol used in this work established a model of advanced hepatic fibrosis as corroborated by METAVIR tests of the histological lesions; by the high levels of the markers α-SMA, CD68, and collagen type I; by functional alterations due to elevated markers of the hepatic lesions; and by alterations of the leukocytes, lymphocytes, and platelets. Finally, transplanted cells in the fibrous liver were detected. We conclude that TAA applied using the protocol introduced in this study induces a good model of advanced liver fibrosis in rats.

Simvastatin Induces Apoptosis And Suppresses Hepatocellular Carcinoma Induced In Rats

Hepatocellular carcinoma (HCC) is a frequent primary aggressive cancer, a crucial cause of cancer-related mortality globally. Simvastatin is a well-known safe cholesterol-lowering medication that has been recently shown to suppress cancer progression. Apoptosis is a well-organized and controlled cellular process that happens both physiologically and pathologically leading to executing cell death. Apoptosis is frequently downregulated in cancer cells. In the present study, we aimed to test the effect of simvastatin on HCC progression. HCC was induced in experimental rats by means of diethylnitrose amine (DEN) and thioacetamide (TAA) injections. Gross examination and liver index along with biochemical analysis of hepatic function were evaluated. Serum alpha-feto protein (AFP) concentration was measured by ELISA. Histopathological examination was used for assessing necroinflammatory scores and fibrosis degree. Apoptosis was assessed using immunohistochemistry (IHC) and quantitative PCR (qPCR). Simvastatin was found to induce apoptosis successfully in HCC and improve liver fibrosis, overall hepatic function, and necroinflammatory score. Simvastatin, therefore, may be a potential adjunctive therapeutic option in clinical settings of treating HCC.

Edaravone protects against liver fibrosis progression via decreasing the IL-1β secretion of macrophages

Edaravone (EDA), a strong novel free radical scavenger, have been demonstrated to exert neurovascular protective effects clinically. Furthermore, EDA can suppress the lung injury, pulmonary fibrosis and skin fibrosis, while the precise effects and mechanisms of EDA on liver injury and fibrosis remain unclear. The effects of EDA on the Thioacetamide (TAA)-induced liver fibrosis were evaluated by sirius red staining, α-SMA immunohistochemistry. The percentages of immune cell subsets were analyzed by flow cytometry. Immunofluorescence assay was performed to identify the fibrotic properties of hepatic stellate cells (HSCs). Western blot and qPCR were used to detect the levels of liver fibrosis-related molecules and IL-1β. EDA displayed a hepatic protective role in TAA-induced chronic liver fibrosis via inhibiting monocyte/macrophages recruitment and IL-1β production of macrophages. Mechanically, EDA inhibited of NF-κB signal pathway and reactive oxygen species (ROS) production in macrophages. Moreover, EDA treatment indirectly suppressed the activation of HSCs by decreasing the IL-1β secretion of macrophages. Together, EDA protects against TAA-induced liver fibrosis via decreasing the IL-1β production of macrophages, thereby providing a feasible solution for clinical treatment of liver fibrosis.

Icariin inhibits thioacetamide-induced osteoclast differentiation through RANKL-p38/ERK-NFAT pathway

This study aims to investigate the therapeutic effect of icariin(ICA) on thioacetamide(TAA)-induced femoral osteolysis in rats. RAW264.7 cells were treated with TAA and ICA. Cell counting kit-8(CCK-8) assay was used to detect cell proliferation, and tartrate-resistant acid phosphatase(TRAP) staining to examine the formation of osteoclasts. The expression of TRAP, cathepsin K, c-FOS, and NFATc1 in RAW264.7 cells was determined by Western blot and immunofluorescence method. Thirty-two SD rats were randomized into the control group, TAA group(intraperitoneal injection of TAA at 300 mg·kg~(-1)), ICA group(gavage of ICA at 600 mg·kg~(-1)) and TAA + ICA group(intraperitoneal injection of TAA at 300 mg·kg~(-1) and gavage of ICA at 600 mg·kg~(-1)). Administration was performed every other day for 6 weeks. Body weight and length of femur were recorded at execution. Pathological injury and osteoclast differentiation of femur were observed based on hematoxylin-eosin(HE) staining and TRAP staining, and the changes of bone metabolism-related indexes alkaline phosphatase(ALP), calcium(Ca), phosphorus(P), magnesium(Mg), and cross-linked N-telopeptide of type Ⅰ collagen(NTX-Ⅰ) in serum were detected. Three-point bending test and micro-CT were applied to evaluate the quality of femur, and Western blot to detect the levels of osteoclast-related proteins TRAP, cathepsin K, RANK, RANKL, p38, p-p38, ERK, p-ERK, JNK, p-JNK, c-Fos, and NFATc1. The results showed ICA could inhibit TAA-induced production of TRAP-positive cells, the expression of osteoclast-related proteins, and nuclear translocation of NFATc1. ICA alleviated the weight loss, reduction of femur length, and growth inhibition induced by TAA in SD rats. ICA ameliorated the decline of femur elastic modulus caused by TAA and significantly restored trabecular bone mineral density(BMD), trabecular pattern factor(Tb.Pf), trabecular number(Tb.N), trabecular thickness(Tb.Th), and structure model index(SMI), thus improving bone structure. Western blot results showed ICA suppressed femoral osteoclast differentiation induced by TAA through RANKL-p38/ERK-NFATc1 signaling pathway. ICA inhibits osteoclast differentiation and prevents TAA-induced osteolysis by down-regulating RANKL-p38/ERK-NFAT signaling pathway.

Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis.

Hepatic fibrosis causes severe morbidity and death. No viable treatment can repair fibrosis and protect the liver until now. We intended to discover the empagliflozin's (EMPA) hepatoprotective efficacy in thioacetamide (TAA)-induced hepatotoxicity by targeting AMPK/SIRT-1 activity and reducing HIF-1α. Rats were treated orally with EMPA (3 or 6 mg/kg) with TAA (100 mg/kg, IP) thrice weekly for 6 weeks. EMPA in both doses retracted the serum GGT, ALT, AST, ammonia, triglycerides, total cholesterol, and increased serum albumin. At the same time, EMPA (3 or 6 mg/kg) replenished the hepatic content of GSH, ATP, AMP, AMPK, or SIRT-1 and mitigated the hepatic content of MDA, TNF-α, IL-6, NF-κB, or HIF-1α in a dose-dependent manner. Likewise, hepatic photomicrograph stained with hematoxylin and eosin or Masson trichrome stain of EMPA (3 or 6 mg/kg) revealed marked regression of the hepatotoxic effect of TAA with minimal injury. Similarly, in rats given EMPA (3 or 6 mg/kg), the immunohistochemically of hepatic photomicrograph revealed minimal stain of either α-SMA or caspase-3 compared to the TAA group. Therefore, we concluded that EMPA possessed an antifibrotic effect by targeting AMPK/SIRT-1 activity and inhibiting HIF-1α. The present study provided new insight into a novel treatment of liver fibrosis.

Ameliorative effect of oregano (Origanum vulgare) versus silymarin in experimentally induced hepatic encephalopathy

Hepatic encephalopathy (HE) is a deterioration of brain function in patients suffering from chronic liver disease, cirrhosis as a result of elevated blood ammonia and the production of pseudo-neurotransmitters. Herein, we investigated the chemical composition of hexane extract from Origanum vulgare (O. vulgare) leaves as well as its possible protective effects against thioacetamide (TAA)-induced HE in rats. GC–MS analysis of the extract revealed tentative identification of twenty-five compounds (82.93%), predominated by cholesten-3-one (27.30%), followed by γ-tocopherol (13.52%), α-tocopherol (5.01%), β-amyrin (5.24%) and α-amyrin (4.89%). Albino rats were distributed into seven groups (n = 7). G1 served as negative control; G2 and G3 served as controls treated with O. vulgare (100 and 200 mg/kg/p.o b.w, respectively); G4 served as TAA-positive control group (100 mg/kg/day/i.p., three alternative days per week for six weeks); G5, G6, and G7 served as TAA -induced HE rat model that received O. vulgare 100, O. vulgare 200, and silymarin (100 mg/kg of SILY, as standard drug), respectively. TAA showed depressive and anxiety-like behaviors in forced swimming test (FST) and reduction of cognitive score in elevated plus-maze test (EPMT) as well as impairment of locomotor and exploratory activities in open-field test (OFT). TAA caused a significant decline in body weight gain; however, the relative liver weight and brain water content were statistically increased. TAA-intoxicated rats showed significant increase of serum biomarker enzymes, proinflammatory cytokines, blood ammonia levels, brain serotonin, acetyl cholinesterase and cellular lipid peroxidation with significant decrease of brain dopamine, norepinephrine, antioxidant status. The hepatoprotective/neuro-protective activities of O. vulgare was found to be comparable with that of SILY in HE rats model. Where, treatment of TAA-intoxicated rats with O. vulgare attenuated anxiety, depressive-related behaviors, and reduced the biochemical changes in HE-induced by TAA. Therefore, O. vulgare could be an excellent hepato-/neuroprotective against hepatic injury and HE via improving the oxidative/inflammatory status through its antioxidant and neuro-modulatory properties and its effect is equal to that of SILY.

Chimeric immune checkpoint protein vaccines inhibit the tumorigenesis and growth of rat cholangiocarcinoma

Cholangiocarcinoma (CCA) isthe second most common primary liver malignancy and carries a dismal prognosis due to difficulties in achieving an optimal resection, and poor response to current standard-of-care systemic therapies. We previously devised a CTLA4-PD-L1 DNA cancer vaccine (DNA vaccine) and demonstrated its therapeutic effects on reducing tumor growth in a thioacetamide (TAA)-induced rat intrahepatic CCA (iCCA) model. Here, we developed a CTLA4-PD-L1 chimeric protein vaccine (Protein vaccine), and examined its effects in the rat iCCA model. In a therapeutic setting, iCCA-bearing rats received either DNA plus Protein vaccines or Protein vaccine alone, resulting in increased PD-L1 and CTLA-4 antibody titers, and reduced iCCA tumor burden as verified by animal positron emission tomography (PET) scans. Treating iCCA-bearing rats with Protein vaccine alone led to the increase of CTAL4 antibody titers that correlated with the decrease of tumor SUV ratio, indicating regressed tumor burden, along with increased <i>CD8</i> and granzyme A (<i>GZMA</i>) expression, anddecreased PD-L1 expression on tumor cells. In a preventive setting,DNA or Protein vaccines were injected in rats before the induction of iCCA by TAA. Protein vaccines induced a more sustained PD-L1 and CTLA-4 antibody titers compared with DNA vaccines, and was more potent in preventing iCCA tumorigenesis. Correspondingly, Protein vaccines, but not DNA vaccines, downregulated PD-L1 gene expression and hindered the carcinogenesis of iCCA. Taken together, the CTLA4-PD-L1 chimeric proteinvaccine may function both as a therapeuticcancer vaccine andas a preventive cancer vaccine in theTAA-induced iCCA rat model.

The role of butyrylcholinesterase in the regulation of cognitive dysfunction in minimal hepatic encephalopathy: A potential blood marker of disease evolution.

Patients with cirrhosis commonly experience minimal hepatic encephalopathy (MHE), and alterations in neurotransmitters have been thought to be related to cognitive function. However, the relationship between alterations in peripheral and central butyrylcholinesterase (BuChE) with MHE disease progression remains unknown. As such, this study was designed to investigate potential changes in peripheral and central BuChE activity and their effects on cognitive function in the context of MHE. We enrolled 43 patients with cirrhosis secondary to hepatitis B, 20 without MHE and 23 with MHE, and 25 with healthy controls (HC). All the selected subjects underwent resting-state functional MRI, and the original images were processed to obtain the regional homogeneity (ReHo) brain maps. Thereafter, the correlation of BuChE activity with ReHo, number connection test of type A (NCT-A), and digital symbol test (DST) scores with MHE patients were analyzed using Person correlation analysis. Meanwhile, we purchased 12 Sprague-Dawley (SD) rats and divided them into an experimental group (n = 6) and a control group (n = 6). The rats in the experimental group were intraperitoneally injected with thioacetamide (TAA) to prepare MHE model rats. After modeling, we used the Morris water maze (MWM) and elevated plus maze (EPM) to assess the cognition function and exploratory behavior of all rats. The activity of serum, hippocampus, and frontal lobe tissue BuChE was detected by ELISA. BuChE activity gradually decreased among the HC, patients with cirrhosis, and MHE groups (all P < 0.01). We observed a linear correlation between serum BuChE and NCT-A and DST scores in MHE patients (all P < 0.01). We noted that BuChE activity can negatively correlate with ReHo values in the left middle temporal gyrus and left inferior temporal gyrus, and positively correlate with ReHo values in the right inferior frontal gyrus, and also found that the peripheral BuChE activity of MHE rats was significantly lower than their control counterparts, and the BuChE activity in frontal lobe extracts was significantly higher than the control rats (all P < 0.05). The altered activity of BuChE may contribute to cognitive impairment in MHE patients, which may be a potential biomarker of disease evolution in the context of MHE.

Early-immediate gene Egr1 is associated with TGFβ1 regulation of epigenetic reader Bromodomain-containing protein 4 via the canonical Smad3 signaling in hepatic stellate cells in vitro and in vivo.

Upon chronic damage to the liver, multiple cytokines stimulate hepatic stellate cells (HSCs), causing the alterations of gene expression profiles and thus leading to HSC activation, a key step in liver fibrogenesis. Activated HSCs are the dominant contributors to liver fibrosis. Bromodomain containing protein 4 (BrD4), an important epigenetic reader, was demonstrated to concentrate on hundreds of enhancers associated with genes involved in multiple profibrotic pathways, thereby directing HSC activation and the fibrotic responses. The present studies were designed to examine the effect of transforming growth factor beta-1 (TGFβ1), the most potent pro-fibrotic cytokine, on BrD4 expression in HSCs and, if so, elucidated the underlying mechanisms in vitro and in vivo. The experiments employed the heterogeneous TGFβ1 knockout (TGFβ1+/- ) mice, gene knockdown in vivo, and a model of thioacetamide (TAA)-induced liver injury. The results revealed that TGFβ1 enhanced BrD4 expression in HSCs, which was mediated, at least, by Smad3 signaling and early-immediate gene Egr1 (early growth response-1). TGFβ1-induced Smad3 signaling increased Egr1 expression and promoted Egr1 binding to BrD4 promoter at a site around -111 bp, promoting BrD4 expression. Egr1 knockdown reduced BrD4 expression in HSCs in a mouse model of TAA-induced liver injury and lessened liver fibrosis. Double fluorescence staining demonstrated a strong increase in BrD4 expression in activated HSCs in fibrotic areas of the human livers, paralleling the upregulation of p-Smad3 and Egr1. This research suggested novel molecular events underlying the roles of the master pro-fibrotic cytokine TGFβ1 in HSC activation and liver fibrogenesis.

One-step solvothermal method synthesizes petal-like Cu2WSx supported on carbon paper used in dye-sensitized solar cells

Sheet-like transition metal sulfides have promising applications in photocatalysis and energy conversion. This study provides a petal-like Cu2WSx nanosheet structure supported on carbon paper (CP) synthesized by a simple one-step solvothermal method. Cu2WSx microstructures with different morphologies were synthesized by solvothermal vulcanization of thioacetamide (TAA) at different concentrations. The Cu2WSx/CP was used as the counter electrode of DSSCs and compared with the Pt FTO electrode. It was proved that Cu2WSx-7 M/CP had the best electrocatalytic performance and obtained 9.01% photoelectric conversion efficiency. The different sulfide concentration changes the morphology of Cu2WSx and continuously affects the specific surface area and catalytic activity of the material. The better electrochemical performance shows that Cu2WSx/CP is expected to become a substitute for expensive Pt CE materials in dye-sensitized solar cells (DSSCs).

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Gibberellic acid (GBA) is a natural plant growth hormone, controlling many developmental processes. In order to explore the protective effects of GBA against Thioacetamide (TAA)-induced acute liver toxicity, thirty male Sprague-Dawley (SD) rats were randomly allocated into six groups (5 rats/group); Normal control (NC): received distilled water (DW) per os (p.o.), GBA only: received (20 mg/kg, p.o.) of GBA, TAA: received DW and TAA (350 mg/kg, i.p.), GBA 5: received GBA (5 mg/kg, p.o.) and TAA (350 mg/kg, i.p.), GBA 10: received GBA (10 mg/kg, p.o.) and TAA (350 mg/kg, i.p.), and GBA 20: received GBA (20 mg/kg, p.o.) and TAA (350 mg/kg, i.p.). Blood and plasma were collected for biochemical analysis while liver tissues were harvested and preserved for histological analysis. The results confirmed the TAA-induced acute liver toxicity by the significantly increased liver enzymes, hypoglycemia, hypoxia, polycythemia, and metabolic acidosis as compared with NC. However, pretreatment of TAA-intoxicated rats with GBA indicated the hepatoprotective effects by reducing liver enzyme levels significantly and alleviating hepatic lesions in a dose-dependent manner

Melatonin attenuates thioacetamide-induced liver fibrosis in male rats through modulation of interleukin-6, interleukin-4, apoptosis and urokinase plasminogen activator receptor-associated protein/Endo180.

Liver fibrosis is a chronic progressive disease, its resolution still unclear, and the current study explored the role of melatonin in modulation of interleukin-6 (IL-6), interleukin-4 (IL-4), transforming growth factor beta1 (TGF-β1) and urokinase plasminogen activator receptor-associated protein/Endo180 (uPARAP/Endo180) pathway in thioacetamide (TAA)-induced hepatotoxicity. Thirty two adult Sprague-Dawley rats were divided into four groups: vehicle control group, TAA-induced liver fibrosis group that was left untreated, melatonin administration before and along with TAA and melatonin along with TAA group. TTA-induced massive liver necrosis, fibrosis around portal tract and increases serum levels of liver enzymes and total bilirubin when compared with control vehicle group. While both melatonin pretreatment and treatment retained liver parenchyma and liver enzymes quite similar to control group and reduced TAA-induced liver injury. Notably, melatonin pretreatment and treatment increased collagen degradation in TAA liver injury by19, 31.7-fold respectively evidence by collagen percentage area. Melatonin also decreased the amount of thiobarbituric acid reactive compounds and retained the reduced glutathione and superoxide dismutase to basal level quite similar to control group. Additionally, melatonin significantly (P value ≤0.05) decreased the levels of TGF-β1, epidermal growth factor (EGF), hydroxyproline, tissues IL-6, caspase-3, and receptor interacting serine/threonine kinase1 (RIPK1), fibrillin-1, and - smooth muscle actin in the liver tissues while significantly (P value ≤0.05) increasing the levels of IL-4 and uPARAP/Endo180. Due to its anti-inflammatory, anti-apoptotic, and antioxidant capabilities as well as its ability to decrease hepatic stellate cell activation and fibrogenesis, these data imply that melatonin has a powerful anti-fibrotic effect.

Chemical Profile of Cyperus laevigatus and Its Protective Effects against Thioacetamide-Induced Hepatorenal Toxicity in Rats.

Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF–MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract’s effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF–MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2′-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress.

Effect of Haegan-jeon on Thioacetamide-Induced Liver Fibrosis

Objective: To investigate the protective effects of Haeganjeon on a thioacetamide (TAA)-induced liver fibrosis mouse model and to determine the Haegan-jeon signaling pathway.Methods: Mice were randomly divided into 4 groups: Normal group (Nor), TAA-induced liver fibrosis group (Con), TAA-induced liver fibrosis group administered 50 mg/kg silymarin (S50), TAA-induced liver fibrosis group administered 200 mg/kg Haegan-jeon (H200). The liver fibrosis mouse model was established by intraperitoneal injection with TAA three times a week for 8 weeks. During the 8 weeks, mice were orally administered silymarin and Haegan-jeon every day. At the end of the study, serum was collected to measure the levels of AST, ALT, ammonia, and myeloperoxidase (MPO). Liver tissue was harvested and analyzed by western blotting and Masson's trichrome staining.Results: Administration of Haegan-jeon suppressed the increase in serum levels of AST, ALT, ammonia, and MPO due to TAA-induced liver fibrosis. Compared to the Con group, the H200 group showed increases in antioxidant-related factors (Nrf2, HO-1, catalase, and GPx-1/2) and decreases in inflammatory-related factors (NF-κB p65, p-IκB-α, Cox-2, iNOS, TNF-α, and IL-1β) in western blots. The H200 treatment inhibited the expression of α-SMA and Collagen I.Conclusions: Haegan-jeon showed a hepatoprotective effect induced by activation of antioxidant-related factors, such as Nrf2, and it regulated the inflammation response by suppression of NF-κB.