CCl4 In Rats Research Articles

Exploring the therapeutic potential of Saudi Kleinia anteuphorbium (L.) DC. Essential oil: Insights into antioxidant, analgesic, and hepatorenal protective effects

Lately, the herb's essential oils have received the intense attention of researchers and pharmaceutical agencies. The chemical composition, antioxidant, analgesic activity, anti-hyperpyrexia, and hepatorenal protective effects of the Kleinia anteuphorbium (L.) DC. Essential oil (KAEO) were evaluated. The KAEO was yanked by steam distillation and subjected to a GC/MS system. The antioxidant powers of KAEO were evaluated by DPPH, NO, and FRAP tests. Besides the anti-hyperpyrexia, the analgesic effects were assessed. Moreover, the hepatorenal curative effects were evaluated in a carbon tetrachloride-rat model. Sixty-eight active components were identified by GC/MS. α-pinene was the most dominant monoterpene in KAEO. KAEO showed anti-hyperpyrexia, anti-captive, and great antioxidant powers through DPPH, NO, and FRAP. The oral LD50 of KAEO was 187.5 mg/kg in rats. Furthermore, KAEO treatment succeeded in reliving the adverse effects of CCL4 in rats as a standard toxic model through reliving the hepatic pathological and oxidative stress and restoring the hepatic and renal functions. Overall, the obtained results demonstrated that KAEO might be used as a potential natural medicine to relieve a variety of modern symptoms and hepatorenal disorders associated with oxidative stress.

Hepatoprotective activity of Mentha rotundifolia aqueous extract against hepatocellular damage induced by CCL4 in rats

This study aims to assess hepatoprotective properties of M. rotundifolia. Decoction was used to prepare the aqueous extract. The preliminary cytotoxicity evaluated against Caco 2 and RAW 264 cells demonstrate no cytotoxic effect. The preventive impact of the extract against liver damage was evaluated by examining blood levels of AST, ALT, ALP, total proteins, and histological alterations in liver tissues. Thirty albino rats were separated into five groups: the first served as normal group, the second was injected by olive oil (3 ml/kg), and the third was injected by CCL4 (3 ml/kg). However, groups IV and V received daily doses of 250 and 500 mg extract/kg bw, respectively before CCL4 injection. The results showed that the administration of the extract led to a marked improvement in plasma biochemical markers and a reduction in symptoms of CCL4-induced liver damage. The extract exhibits hepatoprotective activity, which may be attributed to its phytochemical components.

Biosynthesis of Zinc Oxide Nanoparticles Using Bacillus paramycoides for In Vitro Biological Activities and In Vivo Assessment Against Hepatorenal Injury Induced by CCl4 in Rats.

Recently, impressive developments in the field of nanotechnology have been achieved. The study aimed to synthetize zinc oxide nanoparticles (ZnONPs) from locally isolated terrestrial Bacillus paramycoides (MCCC 1A04098) bacteria and assess its role as antioxidant, antimicrobial, andanticancer agent. The antioxidant activity was done using the percentage of DPPH scavenging method. The antibacterial activity was evaluated against Escherichia coli, Staphylococcus aureus, Bacillus cereus, and Candida albicans. The anti-proliferation assay against hepatocellular carcinoma (HepG2) and human breast cancer (MCF-7) cell lines was estimated by neutral red assay. The apoptotic effect of ZnONP was measured by flow cytometry. The in vivo evaluation was carried out against hepatorenal injuries induced by carbon tetrachloride (CCl4) in rats comparing with silymarin as a reference drug. The oxidative stress markers, liver and kidney function enzyme indices, lipid profile, and the histological features of the liver and kidney were also examined. ZnONPs revealed antioxidant and antibacterial effects. It also exerted cytotoxic and apoptotic effect in a dose dependent manner without any toxicity on normal cell line. ZnONPs improved all the biochemical parameters under investigation to varying degrees, and the histological pictures of the liver and kidney confirmed the results. In conclusion, ZnONPs were successfully synthesized from the terrestrial Bacillus paramycoides and recorded in vitro antioxidant, anticancer, and antibacterial effects as well as in vivo anti-hepatorenal toxicity effects.

Hepatoprotective efficacy of Lagenaria siceraria seeds oil against experimentally carbon tetrachloride-induced toxicity.

The liver is crucial for maintaining normal metabolism in the body. Various substances, such as toxic chemicals, drugs, and alcohol, can damage hepatocyte cells, leading to metabolic imbalances. The experiment aimed to determine the efficacy of Lagenaria siceraria seed oil (LSS) as a hepatoprotective agent against acute hepatotoxicity triggered by carbon tetrachloride (CCl4). A total of 20 rats were randomly separated into four groups. The control group: rats received 2 ml of distilled water orally, followed by 1.25 ml of olive oil intraperitoneally (i.p.) after 30 minutes. CCL4 group: rats were given a single intraperitoneal dose of 1.25 ml/kg b.w. of CCl4 in a 1:1 mixture with olive oil. Silymarin group: received 100 mg of silymarin per kg of b.w. diluted in 2 ml of distilled water orally, followed by CCl4 treatment after 30 minutes. LSS oil group: received LSS oil at 3g/kg b.w. orally, followed by CCl4 treatment after 30 minutes. Blood samples were collected to assess liver enzymes (AST, ALT, and ALP), proteins and bilirubin fractions, and redox status (catalase, reduced glutathione (GSH), and malondialdehyde (MDA)) were assessed in hepatic tissues. Changes in liver histopathological examination were also evaluated. In CCl4-treated rats, there was a significant increase in serum liver marker enzyme activity (ALP, AST, and ALT) along with a significant elevation (p < 0.05) in total bilirubin, indirect bilirubin, and direct bilirubin compared to the control rats. However, all these parameters decreased in the CCl4+ Silymarin and CCl4+LSS groups compared to CCl4-treated rats. There was a significant decline in total protein level and serum albumin in all experimental groups compared to the control, while globulin levels significantly increased in all experimental groups. There was a significant (p < 0.05) reduction in the level of GSH and catalase, with an increase in MDA level in CCl4 rats compared to other rats. Histopathological investigation of the LSS-treated group showed a hepatoprotective effect against CCl4. The study revealed that LSS oil has antioxidant activity against CCl4-induced toxicity.

Extracts from Dacryodes edulis restored renal functions altered by CCl4 in rats

Extracts from Dacryodes edulis restored renal functions altered by CCl4 in rats

Empagliflozin suppresses hedgehog pathway, alleviates ER stress, and ameliorates hepatic fibrosis in rats

Worldwide mortality from hepatic fibrosis remains high, due to hepatocellular carcinoma and end stage liver failure. The progressive nature of hepatic fibrosis from inflammation to cicatrized tissues warrants subtle intervention with pharmacological agents that hold potential. Empagliflozin (Empa), a novel hypoglycemic drug with antioxidant and anti-inflammatory properties, has lately been proposed to have additional antifibrotic activities. In the current study, we examined the antifibrotic effect of the Empa through modulating the activity of hepatic stellate cells by hedgehog (Hh) pathway. We also assessed the markers of inflammatory response and endoplasmic reticulum (ER) stress. Male Albino rats were treated with either CCl4 (0.4 mg/kg twice/week) and/or Empa (10 mg/kg/day) for eight weeks. In this study, CCl4 rats had active Hh signaling as indicated by overexpression of Patched 1, Smoothened and Glioblastoma-2. CCl4 induced ER stress as CHOP expression was upregulated and ERAD was downregulated. CCl4-induced inflammatory response was demonstrated through increased levels of TNF-α, IL-6 and mRNA levels of IL-17 while undetectable expression of IL-10. Conversely, Empa elicited immunosuppression, suppressed the expression of Hh markers, and reversed markers of ER stress. In conclusion, Empa suppressed CCl4-induced Hh signaling and proinflammatory response, meanwhile embraced ER stress in the hepatic tissues, altogether provided hepatoprotection.

Correlation between SDF-1α, CD34 positive hematopoietic stem cells and CXCR4 expression with liver fibrosis in CCl4 rat model

BackgroundOne of the most frequent disorders is liver fibrosis. An improved understanding of the different events during the process of liver fibrosis & its reversibility could be helpful in its staging and in finding potential therapeutic agents.AimThe goal of this research was to evaluate the relationship among CD34 + HPSCs, SDF-1α, and CXCR4 receptor expression with the percentage of the area of hepatic fibrosis.Materials and methodsThirty-six male Sprague-Dawley rats were separated into the control group, liver injury group & spontaneous reversion group. The liver injury was induced by using 2 ml/kg CCl4 twice a week. Flow cytometric examination of CD34 + cells in the blood & liver was performed. Bone marrow & liver samples were taken for evaluation of the SDF-1α mRNA by PCR. Liver specimens were stained for histopathological and CXCR4 immuno-expression evaluation.ResultsIn the liver injury group, the hepatic enzymes, fibrosis area percentage, CXCR4 receptor expression in the liver, CD34 + cells in the blood and bone marrow & the level SDF-1α in the liver and its concentration gradient were statistically significantly elevated with the progression of the liver fibrosis. On the contrary, SDF-1α in the bone marrow was statistically significantly reduced with the development of liver fibrosis. During the spontaneous reversion group, all the studied parameters apart from SDF-1α in the bone marrow were statistically substantially decreased compared with the liver injury group. We found a statistically substantial positive correlation between fibrosis area and all of the following: liver enzymes, CXCR4 receptor expression in the liver, CD34 + cells in the blood and liver, and SDF- 1α in the liver and its concentration gradient. In conclusion, in CCl4 rat model, the fibrosis area is significantly correlated with many parameters in the blood, bone marrow, and liver, which can be used during the process of follow-up during the therapeutic interventions.

Metabolomics study of the hepatoprotective effect of total flavonoids of Mallotus apelta leaf in carbon tetrachloride-induced liver fibrosis in rats.

Mallotus apelta leaf, recorded in the quality standard of Yao Medicinal Material in Guangxi Zhuang autonomous region, is commonly used in the treatment of liver diseases. Total flavonoids of M. apelta leaf (TFM) had good anti-fibrosis activity, but the anti-fibrosis mechanism of TFM is still unclear. Nuclear magnetic resonance technology was used to study the dynamic changes of urine metabolites in CCl4 -induced liver fibrosis before and after TFM treatment. Ingenuity Path Analysis (IPA) was used to find potential target genes for TFM to improve liver fibrosis and verify the expression of target genes by real-time fluorescent quantitative PCR and Western blotting. TFM can significantly reduce serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) levels, improve liver steatosis and reduce inflammation; in urine metabolomics, a total of seven potential biomarkers were found, mainly involving two metabolic pathways; IPA analysis showed that TNF may be a potential target for TFM to improve liver fibrosis induced by CCl4 in rats. This study found that TNF may be a potential target gene for TFM treatment of liver fibrosis, and shows that the anti-fibrosis mechanism of TFM could improve liver fibrosis by regulating the tricarboxylic acid cycle and subtaurine metabolism.

Pleurospermum candollei Methanolic Extract Ameliorates CCl4-Induced Liver Injury by Modulating Oxidative Stress, Inflammatory, and Apoptotic Markers in Rats.

The main objective of this study was to investigate the hepatoprotective potency of the Pleurospermum candollei methanol extract against CCl4-induced liver damage in rats. HPLC technique was used to estimate the presence of polyphenols in the methanol extract of P. candollei (PCM), while proximate analysis revealed the presence of carbohydrates, lipids, and moisture in the extract. The antioxidant potential of PCM was evaluated by 2,2-diphenylpicrylhydrazyl (DPPH) and reducing power assay, which showed a high percentage of inhibition against free radicals. Hepatotoxicity was induced by carbon tetrachloride (CCl4). CCl4 administration reduced the activity of endogenous antioxidants, whereas it increased the production of nitrites and hydrogen peroxide (H2O2) in rats. Furthermore, the level of hepatic markers in serum was also elevated after CCl4 administration. Moreover, the expression of stress-related markers, proinflammatory mediators, and apoptotic genes was enhanced in CCl4-treated rats. Coadministration of PCM along with CCl4 in rats reduced the levels of free radicals and the above genes to normal levels. CCl4 administration caused histopathological alterations in liver tissues, while cotreatment with PCM mitigated liver injuries. These findings suggest that the methanol extract of P. candollei possesses antioxidant and anti-inflammatory properties and can prevent liver injury. Further pharmacological research will be helpful in determining the effectiveness of P. candollei in humans. Development of FDA-approved plant-based anti-inflammatory drugs can help treat patients and reduce the chances of toxicity.

Hepatoprotective Mechanism of Apigenin via Suppression of Oxidative Inflammatory Signaling and Apoptosis against Hepatotoxicity Induced by CCl4 in Rats

Background: Carbon tetrachloride (CCl4) is a critical hepatotoxicant causing liver injury and fibrosis via hepatic production of reactive oxygen species (ROS). Apigenin (APG) is a natural bioactive compound and flavonoid antioxidant. We, therefore, evaluated whether APG could mitigate CCl4-mediated hepatotoxicity. Methods: Rats were randomly divided and administered APG and/or CCl4 in Control group, CCl4 group, APG + CCl4 groups (APG: 10 and 20 mg/kg bw) and APG groups (APG: 10 and 20 mg/kg bw) 2 times per week for 7 consecutive weeks. Result: Rats exposed to CCl4 demonstrated marked increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and monoamine oxidase (MAO) activities and decreased hepatic malondialdehyde (MDA) level compared to control. The hepatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) decreased appreciably. The CCl4 intoxication caused significant increases in inflammatory cytokines (IL-6 and TNF-α) and apoptosis markers, while the anti-inflammatory cytokines (IL-4 and IL-10) decreased with evident histopathological lesions compared to control. APG-dose-dependently-prevented these hepatic alterations.

Protective effect of Ceiba pentandra (L) Gaertn on CCl4-induced oxidative stress and liver damage in rats

BackgroundCeiba pentandra (L.) Gaertn, popularly known as the white silk-cotton tree and popularly used in Chinese and Indian traditional medicine. The bark is used to treat diarrhea, pain, fever, cardiac problems, asthma, and gastrointestinal problems. The present study aimed to evaluate the hepatoprotective and antioxidant effects of ethanol extract of C. pentandra bark (EECP-BK) against CCl4-induced hepatic damage in rats. MethodsPreliminary phytochemical analysis was performed to identify the bioactive compounds. CCl4 (40 mM) induced enzymatic changes at HepG2 cells were adopted for the in-vitro model. HepG2 cells were pretreated with EECP-BK (25, 50, 100, and 200 µg/ml) and standard (silymarin 12.5 µg/ml) respectively. Rat model of CCl4-induced liver damage for adopted for the in-vivo model. Rats were pretreated orally with EECP-BK 200 & 400 mg/kg and standard (silymarin 100 mg/kg) for 7 days. Rats were injected with 1 ml/kg of 50% CCl4 on day 8 to induce hepatic damage and were observed for antioxidant levels and serum biomarkers. In addition, in-silico studies have been performed to explore the binding properties of compounds from EECP-BK with tumor necrosis factor-alpha converting enzyme (TACE) targeting hepatic inflammation ResultsThe phytochemical analysis confirmed the presence of glycoside, steroids, phenols, tannins, and saponins. EECP-BK 200 µg/ml showed the highest protection against CCl4 in HepG2 cells. Similarly, silymarin 12.5 µg/ml showed good protection against CCl4. In rats, EECP-BK up to 2000 mg/kg did produce any toxic signs or mortality. CCl4 injection in rats showed elevated liver enzymatic and bilirubin levels and causes liver damage. It also decreased the SOD, CAT, and GSH levels. Pre-treatment with EECP-BK 400 mg/kg showed a significant reduction in SGPT, SGOT, ALP, and total bilirubin levels and increased SOD, CAT, and GSH levels. Similar results were observed with, silymarin treatment also. Furthermore, EECP-BK showed protection over hepatocyte necrosis induced by CCl4 in rats which is evident by histopathology. Molecular docking studies revealed that acacetin 7-rutinoside binds favorably with the active site of TACE with a binding affinity of -8.8 kJ/mol. ConclusionOur findings supported the antioxidative capability of EECP-BK by showing that it protected the liver from CCl4-induced hepatic damage. Additional research is needed to determine its safety profile and to find its molecular mechanism for therapeutic application.

In silico ADMET, docking, anti-proliferative and antimicrobial evaluations of ethanolic extract of Euphorbia dendroides L.

Euphorbia dendroides can act as a free radical scavenger, so it protects against acute hepatic damage induced by CCl4 in rats. Also, it increases the Tm of salmon testis DNA from 68 °C to about 81 °C. In addition to that, it has shown good antibacterial effect against S. aureus, E. coli, B. subtilis and antifungal effect against A. niger. Along with showing good anticancer effects against HepG2 cells with IC50 = 9.5 μg/mL, HCT-116 cells with IC50 = 13.6 μg/mL and MCF-7 with IC50 = 20.9 μg/mL. The docking study was carried out to explore how genistein, the main compound isolated from the extract of E. dendroides, binds to both VEGFR-2 and DNA active sites. Additionally, our compound displayed very well in Silico predicted ADMET profile. Genistein has better absorption (92.893) compared to sorafenib (84.731) and doxorubicin (62.37), as well as not showing any hepatotoxic effects.

The hepatoprotective effect of aminoguanidine in acute liver injury caused by CCl4 in rats

In this study, the hepatoprotective effect of aminoguanidine in acute liver damage caused by carbon tetrachloride-CCl4 at a dose of 1 mL/kg, i.p. was investigated in experimental rats. Ten days of preventive treatment with aminoguanidine before exposure to toxic CCl4, at a dose of 150 mg/kg, i.p., led to significant reduction in biochemical markers of acute liver injury-AST(p < 0.001), ALT (p < 0.01), SDH (p < 0.05) and reduction in pro-oxidative markers-H2O2 (p < 0.05), TOS (p < 0.01), TBARS, and LOOH (p < 0.001) in relation to rats treated only CCl4. Treatment with aminoguanidine resulted in a significant reduction in the consumption of antioxidant-GR (p < 0.01), GST, GPx, GSH (p < 0.001), and a decrease in pro-inflammatory-TNF-α (p < 0.01), IL-1β, IL-6, NO and NGAL (p < 0.001) markers relative to animals exposed to CCl4 alone. Also, aminoguanidine pre-treatment leads to an increase in arginase activity (p < 0.001), and a decrease in citrulline concentration (p < 0.01), as well as polyamine catabolism enzyme activity-putrescin oxidase and spermine oxidase (p < 0.001) in comparison to the CCl4 group. Aminoguanidine led to a striking reduction of the necrotic field (p < 0.001), and a significant increase in the number of apoptotic hepatocytes (p < 0.001), as well as the proapoptotic markers-BAX and Caspase-3 (p < 0.05), compared to CCl4. The hepatoprotective mechanisms in CCl4 induce hepatotoxicity of aminoguanidine are based on the strong antioxidant effects, inhibition of pro-oxidative and pro-inflammatory mediators, as well as induction of damaged hepatocytes into apoptosis.

Chemical Composition of Tagetes patula Flowers Essential Oil and Hepato-Therapeutic Effect against Carbon Tetrachloride-Induced Toxicity (In-Vivo)

The liver is a crucial organ among body organs due to its wide functions, in particular, detoxification and metabolism. Exposure to detrimental chemicals or viral infections may provoke liver dysfunction and ultimately induce liver tissue damage. Finding natural substances for liver disease treatment to overcome the conventional treatments' side effects has attracted the attention of researchers worldwide. Our current work was conducted to investigate the hepato-therapeutic activities of essential oil (EO) isolated from Tagetes patula flowers. EO was extracted using the hydro-distillation (HD) technique and its chemical composition was identified by GC/MS. Then, the hepatic treatment potential of extracted EO was evaluated in vivo against CCL4 in rats. HD of T. patula flowers yielded highly chemical constituents of EO along with significant antioxidant potential. A coherent molecular network was fashioned via the Global Natural Products Social Molecular Networking (GNPS) to visualize the essential components and revealed that the sesquiterpene (E)-β-caryophyllene was the most predominant volatile constituent which accounted for 24.1%. The treatment of CCL4 led to significant induced oxidative stress markers malonaldehyde, total protein, and non-protein sulfhydryl, as well as elevated serum aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and bilirubin. In addition, it disrupted the level of lipid profile. The post-treatment using T. patula EO succeeded in relieving all toxic effects of CCl4 and recuperating the histopathological signs induced by CCL4. Silymarin was used as a standard hepatoprotective agent. The obtained results demonstrated that the extracted EO exerted high protective activities against the toxicity of CCL4. Moreover, the T. patula flowers EO can be used as a natural remedy to relieve many contemporary liver diseases related to oxidative stress.

Study the effect of alkaloids isolated from Typha domingensis pers. fruit on hepatotoxicity induced by CCl4 in rats

Study the effect of alkaloids isolated from Typha domingensis pers. fruit on hepatotoxicity induced by CCl4 in rats

Antioxidant potency of n-butanol fraction of Ficus glumosa leaves against oxidative stress induced by carbon tetrachloride in the kidneys of rats

Abstract. Abu MS, Yakubu OE, Onuche JI, Tatah SV. 2022. Antioxidant potency of n-butanol fraction on Ficus glumosa leaves against oxidative stress induced by carbon tetrachloride in the kidneys of rats. Nusantara Bioscience 14: 40-46. The kidneys play several essential roles in the body, including regulating the water and ions reabsorb from glomerular filtrate in kidney tubules. It is controlled by several hormones such as antidiuretic hormone (ADH), aldosterone, and angiotensin II. This report presented the repairing effect of n- butanol fraction of Ficus glumosa Delile on nephrotoxicity induced by CCl4 in rats. Rats were divided into 7 groups of 5 animals each. Group 1 and 2 were used as normal and vehicle controls, respectively. Group 3 was induced but treated with neither extract nor standard drug. However, Groups 3, 4, and 5 were induced by CCl4 and administered with varying doses of the n-butanol fraction. Group 6 was induced by CCl4 and treated with a standard antioxidant drug. The results showed that treatments with an n-butanol fraction of F. glumosa leaves and silymarin significantly (p&lt;0.05) restore the activities of SOD, GPx, and CAT comparable to normal values, i.e., 2.10±0.07 U/L, 43.8±2.49 U/L, and 34.2±2.59 U/L, respectively. In addition, the treatments reduce the MDA level in the kidney of rats treated with n-butanol fraction comparable to 0.34±0.05 mmol/L in the normal rats. Similarly, there was a significant (p&lt;0.05) reduction of urea from 5.24 mg/dL to 3.5 mg/dL (standard value) in the treated groups. Creatinine significantly (p&lt;0.05) reduced from 71.2 mg/dL in the treated groups to 43.3 mg/dL in the normal group. Electrolytes, Na+, K+, and Cl- levels in the CCl4-induced rats after administration of n-butanol fraction of F. glumosa leaves significantly (p&lt;0.05) decreased to 137.8±2.59 mmol/L, 3.98±0.54 mmol/L, and 92.8±1.92 mmol/L respectively. The significant reversal of the rats' biochemical parameters can be ascribed to the ameliorative potency of the n-butanol fraction of methanol extract of F. glumosa leaves on the glomerular and tubular cells, which may have improved renal function in the injured kidney.

Evaluation of Anti-inflammatory and Antioxidant Effects of Sumatriptan on Carbon Tetrachloride-induced Hepatotoxicity in Rats.

The liver detoxifies and metabolizes many drugs and xenobiotics which may cause hepatotoxicity due to some toxic agents. Carbon tetrachloride (CCl4) is metabolized in cytochrome P450 and its reactive radical metabolites cause lipid peroxidation, cellular injury, and apoptosis. Sumatriptan (SUM), 5-HT1B/1D receptor agonist, had anti-inflammatory and anti-oxidant effects. In this research the effect of SUM pre-treatment against CCl4-induced hepatotoxicity was examined. Adult rats received SUM (0.1, 0.3 and 1 mg/kg; i.p.) for 3 consecutive days before CCl4 (2 ml/kg; i.p. on the 3rd day). The aminotransferases serum levels, tissue levels of anti-oxidant and pro-inflammatory markers and histopathological examination were evaluated. SUM (0.3 mg/kg) prevented significantly the elevation of aminotransferases versus the control group (CCl4 group) (P<0.0001) and also, reversed meaningfully the changes of the MPO, MDA, SOD and CAT, IL-1β and TNF-α levels. Additionally, CCl4-intoxication resulted to the disruption of lobular and cellular structures and inflammation in histopathological evaluation which is prevented by SUM (0.3 mg/kg). These data revealed that SUM (0.3 mg/kg), but no at doses 0.1 and 1 mg/kg, decreases the hepatotoxicity of induced by CCl4 in rats.

Pancreas stiffness in liver cirrhosis is an indicator of insulin secretion caused by portal hypertension and pancreatic congestion.

Portal hypertension induces pancreatic congestion and impaired insulin secretion in patients with liver cirrhosis (LC). However, its mechanism is unclear, with no established noninvasive imaging method for the evaluation of its pathogeneses. The present study focused on pancreas stiffness, as assessed by shear wave elastography (SWE), and examined its association with portal hypertension and insulin secretion. Shear wave elastography and contrast-enhanced ultrasonography were utilized to evaluate pancreas stiffness and congestion, respectively. A glucagon challenge test was used for insulin secretion assessment. Furthermore, rat models of carbon tetrachloride (CCl4 )-induced LC and portal hypertension were used to identify the direct effects of pancreatic congestion. Immunohistochemistry staining of the pancreas was carried out on human autopsy samples. Pancreas stiffness measured by SWE was higher in patients with LC than in controls and showed significant correlation with pancreatic congestion. The glucagon challenge test indicated a lower value for the change in C-peptide immunoreactivity in the LC group, which was inversely correlated with pancreas stiffness and congestion. Additionally, portal hypertension and insulin secretion dysfunction were confirmed in CCl4 rat models. Autopsy of human samples revealed congestive and fibrotic changes in the pancreas and the relationship between insulin secretion and their factors in patients with LC. In patients with LC, pancreas stiffness measured by SWE could be a potential noninvasive test for evaluating pancreatic congestion and fibrosis due to portal hypertension. Moreover, it was associated with impaired insulin secretion, and could aid in guiding the treatment for hepatogenous diabetes.

Selenium enriched yeast and Gum Arabic combination attenuate oxidative liver damage via suppression of oxidative stress, inhibition of caspase-3 and pro-inflammatory genes expression in carbon tetrachloride-intoxicated rats

In this study we investigated the potential synergistic effects of Gum Arabic (GA) and Selenium enriched yeast (SY) combination on the carbon tetrachloride (CCl4) -caused oxidative damage in the liver of rats. The rats were separated into 5 groups (8 animals per group) and subjected to GA, SY and GA + SY diets following CCl4 injection. The results showed that GA + SY supplementation demonstrated higher protective antioxidative properties than the supplementation of either GA or SY alone, as manifested by lesser activities of serum alkaline phosphatase (ALP), serum transaminase, hepatic malondialdehyde (MDA), and augmented the hepatic activities of superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) consistent with up-regulation of antioxidant-related genes including glutathione peroxidase 1 (GPX1), superoxide dismutase (SOD1), and heat shock protein 70 (HSP70) in CCl4-intoxicated rats. Furthermore, GA + SY supplementation revealed mild pathological damage and effectively attenuated expression levels of the proinflammatory genes including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor- α (TNF-α). Moreover, GA + SY supplementation alleviated CCl4-induced hepatocytes apoptosis via suppression of caspase-3 expression. We concluded that GA + SY combination displayed strong protective and antioxidative effects against hepatotoxic injury caused by CCl4 in rats via its ability to suppress the oxidative stress, inhibit the caspase-3 and pro-inflammatory genes expression.

Elevated miR-129-5p attenuates hepatic fibrosis through the NF-κB signaling pathway via PEG3 in a carbon CCl4 rat model.

Hepatic fibrosis is a reversible scaring response to chronic liver injury. MicroRNA (miR)-129-5p might regulate fibrosis-related gene expression. This study is performed to decipher, potential of miR-129-5p to influence the progression of hepatic fibrosis in a carbon tetrachloride (CCl4) rat model. Rat hepatic fibrosis was successfully established by subcutaneous injection of 50% CCl4. RT-qPCR revealed that miR-129-5p was poorly expressed and PEG3 was highly expressed in hepatic fibrosis tissues. As reflected by dual-luciferase reporter gene assay, miR-129-5p targeted and reduced the expression of PEG3. Thereafter, miR-129-5p antagomir or short hairpin RNA against paternally expressed gene 3 (PEG3) was adopted for gain- and loss-of-function assay to determine the molecular regulatory mechanism of miR-129-5p. Moreover, we detected the expression of nuclear factor kappa B (NF-κB) signaling pathway-related proteins and apoptosis-related factors, and made a serological analysis of the rat serum samples. Results showed that upregulated miR-129-5p or downregulated PEG3 led to reduction of the histological changes of liver cirrhosis and lowered the apoptosis rate, via downstream effects on the NF-κB signaling pathway. Thus, the hepatic fibrosis induced by CCl4 can be rescued by upregulated miR-129-5p or downregulated PEG3 expression.