Pathological Changes In Liver Research Articles

Lp-PLA2 silencing ameliorates inflammation and autophagy in nonalcoholic steatohepatitis through inhibiting the JAK2/STAT3 pathway.

Nonalcoholic steatohepatitis (NASH), a common cause of liver-related morbidity and mortality worldwide, is characterized by inflammation and hepatocellular injury. Our research focuses on lipoprotein-associated phospholipase A2 (Lp-PLA2), an inflammation-related biomarker that has recently garnered interest in the context of NASH due to its potential roles in disease pathogenesis and progression. We established a NASH mouse model using a high-fat diet (HFD) and treated it with sh-Lp-PLA2 and/or rapamycin (an mTOR inhibitor). Lp-PLA2 expression in NASH mice was detected by qRT-PCR. Serum levels of liver function parameters and inflammatory cytokines were detected using corresponding assay kits. We examined pathological changes in liver using hematoxylin-eosin, oil red O, and Masson staining, and observed autophagy through transmission electron microscopy. The protein levels of Lp-PLA2, mTOR, light chain 3 (LC3) II/I, phosphorylated Janus kinase 2 (p-JAK2)/JAK2, and phosphorylated signal transducer and activator of transcription 3 (p-STAT3)/STAT3 were determined by western blotting. Kupffer cells extracted from C57BL/6J mice were treated to replicate NASH conditions and treated with sh-Lp-PLA2, rapamycin, and/or a JAK2-inhibitor to further verify the roles and mechanisms of Lp-PLA2 in NASH. Our data indicate an upregulation of Lp-PLA2 expression in HFD-induced NASH mice. Silencing Lp-PLA2 in NASH mice reduced liver damage and inflammation markers (aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglycerides (TG), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6)), while increasing IL-10 levels, an anti-inflammatory cytokine. Additionally, Lp-PLA2 silencing decreased lipid and collagen accumulation and promoted autophagy. The beneficial effects of sh-Lp-PLA2 on NASH were enhanced by rapamycin. Furthermore, Lp-PLA2 silencing resulted in the downregulation of the expression of p-JAK2/JAK2 and p-STAT3/STAT3 in NASH mice. Similar results were observed in Kupffer cells treated under NASH conditions; Lp-PLA2 silencing promoted autophagy and repressed inflammation, effects which were potentiated by the addition of rapamycin or a JAK2-inhibitor. Our findings suggest that silencing Lp-PLA2 promotes autophagy via deactivating the JAK2/STAT3 signaling pathway, thereby restraining NASH progression. This highlights the potential therapeutic value of targeting Lp-PLA2, adding a new dimension to our understanding of NASH pathogenesis and treatment strategies.

Discussion on the Mechanism of Gandoufumu Decoction Attenuates Liver Damage of Wilson's Disease by Inhibiting Autophagy through the PI3K/Akt/mTOR Pathway Based on Network Pharmacology and Experimental Verification.

Gandoufumu decoction (GDFMD) is a traditional Chinese medicine that has been widely used to treat Wilson's disease (WD) liver damage patients. However, its specific molecular mechanism currently remains unclear. Autophagy as a key contributor to WD liver damage has been intensely researched in the recent years. Therefore, the aim of this present study is to explore the effect of GDFMD on autophagy in WD liver damage, and the final purpose is to provide scientific evidence for GDFMD treatment in WD liver damage. The molecular mechanisms and autophagy-related pathways of GDFMD in the treatment of WD liver damage were predicted using network pharmacology. Copper assay kit was used to determine copper content in serum. Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify serum levels of liver enzymes and oxidative stress-related indicators. Hematoxylin-eosin (HE), Masson, and Sirius red staining were used for the characterization of liver pathological changes. Transmission electron microscopy, immunofluorescence, and Western blot analyses were used to evaluate autophagy activity. The impact of the GDFMD on typical autophagy-related pathway (PI3K/Akt/mTOR pathway) molecules was also assessed via Western blot analysis. GDFMD effectively attenuated serum liver enzymes, oxidative stress, autophagy, and degree of hepatic histopathological impairment and reduced serum copper content. Through network pharmacological approaches, PI3K/Akt/mTOR pathway was identified as the typical autophagy-related pathway of GDFMD in the treatment of WD liver damage. Treatment with GDFMD activated the PI3K/Akt/mTOR pathway, an effect that was able to be counteracted by LY294002, a PI3K antagonist or Rapa (rapamycin), an autophagy inducer. GDFMD imparted therapeutic effects on WD through autophagy suppression by acting through the PI3K/Akt/mTOR pathway.

The Presence and Severity of NAFLD are Associated With Cognitive Impairment and Hippocampal Damage.

Although cognitive impairment in nonalcoholic fatty liver disease (NAFLD) has received attention in recent years, little is known about detailed cognitive functions in histologically diagnosed individuals. This study aimed to investigate the association of liver pathological changes with cognitive features and further explore the underlying brain manifestations. We performed a cross-sectional study in 320 subjects who underwent liver biopsy. Among the enrolled participants, 225 underwent assessments of global cognition and cognitive subdomains. Furthermore, 70 individuals received functional magnetic resonance imaging scans for neuroimaging evaluations. The associations among liver histological features, brain alterations, and cognitive functions were evaluated using structural equation model. Compared with controls, patients with NAFLD had poorer immediate memory and delayed memory. Severe liver steatosis (odds ratio, 2.189; 95% CI, 1.020-4.699) and ballooning (OR, 3.655; 95% CI, 1.419-9.414) were related to a higher proportion of memory impairment. Structural magnetic resonance imaging showed that patients with nonalcoholic steatohepatitis exhibited volume loss in left hippocampus and its subregions of subiculum and presubiculum. Task-based magnetic resonance imaging showed that patients with nonalcoholic steatohepatitis had decreased left hippocampal activation. Path analysis demonstrated that higher NAFLD activity scores were associated with lower subiculum volume and reduced hippocampal activation, and such hippocampal damage contributed to lower delayed memory scores. We are the first to report the presence and severity of NAFLD to be associated with an increased risk of memory impairment and hippocampal structural and functional abnormalities. These findings stress the significance of early cognitive evaluation in patients with NAFLD.

Plantamajoside alleviates acute sepsis-induced organ dysfunction through inhibiting the TRAF6/NF-κB axis

Context Plantamajoside (PMS) possesses rich pharmacological characteristics that have been applied to remedy dozens of diseases. However, the understanding of PMS in sepsis remains insufficient. Objective Role of PMS in sepsis-regulated organ dysfunction and potential mechanisms were investigated. Materials and methods Thirty C57BL/6 male mice were adaptive fed for three days and used to establish acute sepsis model by caecal ligation and perforation (CLP). These experimental mice were divided into Sham, CLP, CLP + 25 mg PMS/kg body weight (PMS/kg), CLP + 50 mg PMS/kg and CLP + 100 mg PMS/kg (n = 6). The pathological and apoptotic changes of lung, liver and heart tissues were observed via HE and TUNEL staining. The injury-related factors of lung, liver and heart were detected by corresponding kits. ELISA and qRT-PCR were applied to assess IL-6/TNF-α/IL-1β levels. Apoptosis-related and TRAF6/NF-κB-related proteins were determined using Western blotting. Results All doses of PMS enhanced the survival rates in the sepsis-induced mouse model. PMS remitted sepsis-mediated lung, liver and heart injury through prohibiting MPO/BALF (70.4%/85.6%), AST/ALT (74.7%/62.7%) and CK-MB/CK (62.3%/68.9%) levels. Moreover, the apoptosis index (lung 61.9%, liver 50.2%, heart 55.7% reduction) and IL-6/TNF-α/IL-1β levels were suppressed by PMS. Furthermore, PMS lowered TRAF6 and p-NF-κB p65 levels, whereas TRAF6 overexpression reversed the protective influences of PMS in organ injury, apoptosis and inflammation triggered by sepsis. Discussion and conclusions PMS suppressed sepsis-induced organ dysfunction by regulating the TRAF6/NF-κB axis, and PMS treatment may be considered as a novel strategy for sepsis-caused damage in future.

Hepatoprotective Effect of Myricetin following Lipopolysaccharide/DGalactosamine: Involvement of Autophagy and Sirtuin 1.

Acute liver injury (ALI) is a critical and fatal disorder associated with excessive oxidative stress and inflammation, ultimately leading to the death of hepatocytes. Myricetin is a bioflavonoid in some berries, including blueberries and strawberries, with anti-inflammatory, antioxidant and anti-apoptotic properties. In the current research, the hepatoprotective potential of myricetin was studied in the LPS/D-GalN model of ALI in C57BL/6 mice. For inducing liver injury, D-GalN (400 mg/kg) and LPS (50 µg/kg) were injected via intraperitoneal route and myricetin was orally administered (25 or 100 mg/kg/day) for two days before inducing injury. Functional indices of liver dysfunction along with hepatic apoptotic, autophagic, oxidative stress and inflammatory factors were measured. Myricetin (100 mg/kg) reduced the fatality rate of animals and pathological liver changes and suitably lowered serum levels of total bilirubin, 8-OH-dG, ALT, AST and ALP in addition to decreasing apoptotic, oxidative and inflammatory factors, NOX, NLRP3, caspase 3, MPO and enhancing some antioxidants. Besides, myricetin improved the hepatic level and activity of sirtuin 1 and reversed inappropriate alterations of autophagic parameters, including LC3 II, Beclin 1, and P62. The beneficial effects of myricetin were attenuated after co-treatment with the autophagy inhibitor 3- methyladenine. This study indicates the hepatoprotective potential of myricetin that can be ascribed to its down-regulation of oxidative, apoptotic, and inflammatory factors and upregulation of antioxidants besides its partial regulation of sirtuin 1 and autophagic pathway.

Clinicopathologic characteristics of liver inflammation and fibrosis in 310 patients with chronic hepatitis B.

Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.

Bone marrow mesenchymal stem cell-derived small extracellular vesicles promote liver regeneration via miR-20a-5p/PTEN.

Balancing hepatocyte death and proliferation is key to non-transplantation treatments for acute liver failure (ALF), which has a high short-term mortality rate. Small extracellular vesicles (sEVs) may act as mediators in the repair of damaged liver tissue by mesenchymal stem cells (MSCs). We aimed to investigate the efficacy of human bone marrow MSC-derived sEVs (BMSC-sEVs) in treating mice with ALF and the molecular mechanisms involved in regulating hepatocyte proliferation and apoptosis. Small EVs and sEV-free BMSC concentrated medium were injected into mice with LPS/D-GalN-induced ALF to assess survival, changes in serology, liver pathology, and apoptosis and proliferation in different phases. The results were further verified in vitro in L-02 cells with hydrogen peroxide injury. BMSC-sEV-treated mice with ALF had higher 24h survival rates and more significant reductions in liver injury than mice treated with sEV-free concentrated medium. BMSC-sEVs reduced hepatocyte apoptosis and promoted cell proliferation by upregulating miR-20a-5p, which targeted the PTEN/AKT signaling pathway. Additionally, BMSC-sEVs upregulated the mir-20a precursor in hepatocytes. The application of BMSC-sEVs showed a positive impact by preventing the development of ALF, and may serve as a promising strategy for promoting ALF liver regeneration. miR-20a-5p plays an important role in liver protection from ALF by BMSC-sEVs.

Effects of supplemented multicomponent mycotoxin detoxifying agent in laying hens fed aflatoxin B1 and T2-toxin contaminated feeds

The present study was conducted to determine the ability of multicomponent mycotoxin detoxifying agent (MMDA) in feed to prevent the gastrointestinal absorption of aflatoxin B1 (AFB1) and T2-toxin supplemented via spiked maize. For comparisons, hens were fed with uncontaminated basal diet without or with addition of MMDA at 2 g/kg feed. The trial consisted of 105 laying hens (Lohmann Brown) without obvious signs of disease allocated to 7 treatment groups in 35 pens. Responses were demonstrated on laying performance and health status throughout the 42 d experimental period. The results of laying performance indicated significantly decreased egg mass with increasing mycotoxin (AFB1 and T2-toxin) levels up to the maximum tolerated dosage, however simultaneous presence of MMDA laying performance was slightly modified linearly to increasing application. Dose-dependent pathological changes in liver and kidneys and their relative weights, changes in blood parameters and reduced eggshell weights were observed in the hens fed AFB1 and T2-toxin. The pathological changes in the hens fed with diets containing AFB1 and T2-toxin without MMDA were significantly higher as compared with the control group, but eggshell stability was not affected. The contents of AFB1, T2-toxin and their metabolites in liver and kidney tissues were significantly decreased in the hens supplemented with MMDA at 2 and 3 g/kg in feed. MMDA supplementation significantly reduced the deposition of AFB1, T2-toxin and their metabolites in liver and kidneys at the maximum tolerated dosage (2 and 3 g/kg) indicating specific binding to AFB1 and T2-toxin in the digestive tract as compared to the corresponding diets without MMDA. Exposure of AFB1 and T2-toxin indicated significantly decreased egg mass with increasing mycotoxin levels up to the maximum tolerated dosage because of the significantly reduced egg production. Therefore, in this study, MMDA could reduce negative effects of feeding AFB1 and T-2 to laying hens.

Abietic acid inhibits acetaminophen-induced liver injury by alleviating inflammation and ferroptosis through regulating Nrf2/HO-1 axis.

Abietic acid has been known to exhibit anti-inflammatory activity. This study was designed to investigate the protective effects of abietic acid on acetaminophen (APAP)-induced liver injury. The data demonstrated that abietic acid significantly ameliorated APAP-induced liver pathological changes, TNF-α and IL-1β production. APAP could increase malondialdehyde (MDA) and Fe2+ levels, and decrease ATP and glutathione (GSH) levels, as well as glutathione peroxidase 4 (GPX4) and xCT expression. However, these changes induced by APAP were prevented by abietic acid, indicating abietic acid could inhibit APAP-induced ferroptosis. Furthermore, abietic acid inhibited APAP-induced NF-κB activation and increased the expression of Nrf2 and HO-1. Additionally, the inhibitory effects of abietic acid on APAP-induced liver injury were prevented in Nrf2-/- mice. In vitro, the inhibition of abietic acid on APAP-induced inflammation and ferroptosis were reversed when Nrf2 was knockdown. In summary, abietic acidexhibited a therapeutic effectagainst liver injury by attenuating inflammation and ferroptosis.

Glaucocalyxin A attenuates carbon tetrachloride-induced liver fibrosis and improves the associated gut microbiota imbalance.

Liver fibrosis refers to the pathophysiological process of dysplasia on the connective tissue of the liver, caused by a variety of pathogenic factors. Glaucocalyxin A (GLA) has anticoagulation, antibacterial, anti-inflammation, antioxidant and antitumour properties. However, whether GLA ameliorates liver fibrosis or not is still unclear. In this study, a liver fibrosis model was established using male C57BL/6 mice. The mice were treated with 5 and 10 mg/kg GLA via intraperitoneal injection, respectively. The ones that were treated with 5 mg/kg OCA were used as the positive control group. The levels of liver function, liver fibrosis biomarkers and liver pathological changes were then evaluated. We also explored the effects of GLA on inflammatory response and liver cell apoptosis. In addition, we investigated the gut microbiota mechanisms of GLA on liver fibrosis. The results from this study that GLA could significantly decrease the level of liver function (AST, ALT, TBA) and liver fibrosis (HA, LN, PC-III, IV-C). On the other hand, a significant decrease in inflammation levels (IL-1β, TNF-α) were also noted. GLA also improves CCl4-induced pathological liver injuries and collagen deposition, in addition to decreasing apoptosis levels. In addition, an increase in the ratio of Bacteroidetes and Firmicutes in liver disease was also observed. GLA also improves the gut microbiota. In conclusion, GLA attenuates CCl4-induced liver fibrosis and improves the associated gut microbiota imbalance.

JianPi-QingHua formula attenuates nonalcoholic fatty liver disease by regulating the AMPK/SIRT1/NF-κB pathway in high-fat-diet-fed C57BL/6 mice

Context Non-alcoholic fatty liver disease (NAFLD) is a common liver disease, accompanied by liver lipid accumulation and inflammation. JianPi-QingHua formula (JPQH), a Chinese herbal formula, exhibits effects on obesity and T2DM. However, the hepatoprotective effect of JPQH has not been elucidated. Objective To investigate the hepatoprotective effect of JPQH in NAFLD induced by a high-fat diet (HFD) in mice. Materials and methods C57BL/6J mice were divided into four groups and fed a normal-fat diet (ND), high-fat diet (HFD), HFD + JPQH (2.5 g/kg), or HFD + metformin (300 mg/kg) for 6 weeks, respectively. Furthermore, the body weight, epididymal fat mass, blood glucose, and liver weight were measured. Serum total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were performed. Hematoxylin and eosin staining and Oil Red O staining were observed in hepatic histopathological changes. Western blotting and quantitative real-time polymerase chain reaction were utilized to assess the key protein expression of hepatic lipid metabolism and inflammation. Results Compared with the HFD group, JPQH could reduce body weight, epididymal fat mass, blood glucose and liver weight (p < 0.05), and markedly decreased the levels of serum TC, TG, ALT, AST (p < 0.05). Additionally, JPQH improved liver pathological changes. Consistent with the hepatic histological analysis, JPQH intervention suppressed lipid accumulation and inflammatory responses. Mechanistically, JPQH boosted SIRT1/AMPK signalling, and attenuated NF-κB pathway, which suppressed inflammatory responses. Discussion and conclusions These findings indicate that JPQH supplementation protected against HFD-induced NAFLD by regulating SIRT1/AMPK/NF-κB pathway, which provides a theoretical basis for the clinical treatment of patients with NAFLD.

Carbon quantum dot fluorescent probe for labeling and imaging of stellate cell on liver frozen section below freezing point

The targeted labeling imaging of stellate cells on liver frozen section by immunofluorescence is a very promising visualization technique to study the distribution of stellate cells in the liver. In this study, water soluble carbon quantum dots that can emit blue, green and yellow fluorescence are synthesized by the hydrothermal method, and their sizes are 3.2, 3.7, and 4.3 nm, respectively. The three carbon quantum dots have good fluorescence stability, and the quantum yields are 36.1%, 26.3% and 21%, respectively. When the mass fraction of KCl in the blue carbon quantum dot dispersion system is 13%, it still maintains the liquid state at −30 °C. The final fluorescent probe is obtained after the carbon quantum dots are coupled with the secondary antibody, spectral characterizations confirm that the conjugate probe still maintains protein immunoactivity and has good stability. Cell experiments prove that the probe has good biocompatibility, the rabbit anti-mouse Desmin antibody is used as the primary antibody, the results of cellular immunofluorescence imaging and flow cytometry show that the probe can specifically label hepatic stellate cell at −20 °C. The results of liver frozen section experiments show that hepatic stellate cell can be specifically targeted and labeled by the fluorescent probe. This labeling technology provides an important technical means for elucidating the structure and function of the liver at the cellular level, exploring the liver pathological change, and designing and developing drug.

Ameliorative effect of resveratrol against cymoxanil-mancozeb induced toxicity in rats.

This study was conducted to evaluate the cymoxanil-mancozeb (CM) toxicity and investigate the ameliorative effect of resveratrol (Res) against cymoxanil-mancozeb toxicity. Forty rats were divided into four groups; the first group was used as a control group, the second group was exposed to Res only at a dose of 20 mg/kg body weight for 4 weeks, and the third group was administered CM only at a dose of 799 mg/kg body weight for 4 weeks, The fourth group was co-treated with Res+CM for 4 weeks. Blood samples were analyzed for hematological and biochemical parameters. The comet assay was done on liver and blood specimens and histopathological examinations of the liver and intestine. The results demonstrated that CM exposure caused a significant increase in WBCs, lymphocytes, granulocytes, monocytes ALT, AST, ALP, and GGT, and total cholesterol and triglycerides levels accompanied by a decrease in HGB, HCT, RBCs and MCV, MCH, MCHC, HDL and glucose levels with no significant DNA damage in liver and blood. CM mixture induced severe pathological changes in small intestine and liver. Co-treatment of Res with CM improved hematological picture, lipid and glucose profiles also liver enzymes and decreased changes in the architecture of the liver and intestine.

Standardized extract of Sanguisorba minor attenuates injury in aging rat model via the Nrf2/HO‑1 pathway.

Aging promotes damage to vulnerable organs like brain and liver. Sanguisorba minor has been traditionally used to cure various ailments. Few studies have reported pharmacological activities of this medicinal plant. This research aimed to investigate the effects of Sanguisorba minor extract (SME) on brain and liver injury in aging rats and identify the underlying mechanisms. The aging model was developed by subcutaneously injecting D‑galactose and simultaneously treating them with SME. After biochemical and pathological assessments, mRNA expression levels of nuclear factor‑erythroid factor 2‑related factor 2 (Nrf2) and Nrf2‑ regulated gene, heme oxygenase‑1 (HO‑1), in the brain and liver tissues were determined. As a result, malondialdehyde and acetylcholinesterase levels were elevated while total thiol content and superoxide dismutase were reduced in the aging rats. Treatment with the extract remarkably attenuated oxidative injury and pathological changes in liver and brain tissues. Concomitantly, the extract up‑regulated Nrf2 and HO‑1 genes. Our findings exhibited SME may improve the aging‑related brain and liver damage through the Nrf2‑HO‑1 pathway.

Antioxidant activity of raw and cooked onions in rabbit doe nutrition

The aim of this research is to examine how raw and cooked onions affect some antioxidant enzymes and some tissues in female rabbits. Twenty-four female albino rabbits weighing (1-1.5 Kg), (5-6 months age), non-pregnant, were used for the experiment, and they were divided into three groups for a duration of 28 days. A 20 g/kg raw onion and same amount of cooked onion were added to the second and third groups’ diets respectively for comparison of results with control groups without any addition of onion. Results showed that diets supplemented with raw and cooked onion significantly increased the superoxide dismutase (SOD) activity. The cooked onion group showed normal and no pathological changes in liver, kidney, and heart tissues, while liver tissues of both control and raw onion groups suffered extreme congestion in the central veins of the liver lobules and in kidney tissues of only control rabbits, developed hemorrhagic foci was observed. In the control and raw onion groups, the heart tissue showed the development of hemorrhagic foci and necrosis in the heart muscle fibers. In conclusion, both raw and cooked onions boosted the activity of SOD enzyme, but the cooked onions showed to be more effective than raw at protecting liver, kidney, and heart tissues against cell necrosis caused by oxidative processes.

Metabonomic analysis of the anti-hepatic fibrosis effect of Ganlong capsules.

Context: Hepatic fibrosis is a progressive condition, often attributed to metabolic disorders, which may promote cirrhosis and liver cancer. Ganlong capsules derived from Periplaneta Americana have been shown to have a therapeutic effect on liver fibrosis but little is known about the molecular mechanisms involved. Objective: To investigate the metabolic modulations produced by Ganlong capsules in liver fibrosis. Methods: A carbon tetrachloride- (CCl4) treated rat model of liver fibrosis was constructed and Ganlong capsules administered. Levels of serum liver enzymes and pathological changes to the liver were evaluated. Non-targeted metabolomics of liver, serum and urine were used to investigate metabolic regulatory mechanisms. Results: Ganlong capsules reduced serum levels of liver enzymes and improved pathological changes in the rat model of fibrosis. Non-targeted metabolomics showed that Ganlong capsules ameliorated pathways of glycerophospholipid, linoleic acid, pyrimidine, glycine, butyric acid, valine, serine, threonine and arachidonic acid metabolism and biosynthesis of leucine and isoleucine. Such pathways influence the development of CCl4-induced liver fibrosis. Conclusion: Ganlong capsules had an anti-fibrotic hepatoprotective effect and regulated lipid, butyric acid, amino acid and arachidonic acid metabolism.

Comparative histopathology of livers from Baltic cod infected with the parasitic nematode Contracaecum osculatum

Infection levels with the parasitic nematode Contracaecum osculatum in Eastern Baltic cod have increased in the last decades. Eastern Baltic cod is transport host for this parasite that has a high affinity for the liver of the fish. The liver is a highly vital organ and damage to the liver tissue can result in reduced functionality of the organ. Previous studies have revealed that cod with high infections loads reveal impaired physiological performance, reduced nutritional condition and show signs of having a liver disease. Yet, little is known about the pathological changes and inflammatory reactions of the cod liver related to the infections. In this study, we performed histological examinations on 30 Baltic cod livers caught in the eastern part of the Baltic Sea (length; 38 ± 0.9cm, weight; 454 ± 34.8gram) and three Sound cod livers (length; 63 ± 2.9cm, weight; 3396 ± 300.2gram) to categorize the degree of inflammation and its relation to pathological changes in infected cod livers. We further investigated how C.osculatum infection levels varied with intensity of inflammation and co-infections. We found that high infection loads with C.osculatum caused severe inflammation in the liver tissue of cod and reduced fat content of the hepatocytes. Conspicuous amounts of glycogen were found in the muscle and intestinal epithelial cells of the nematodes and parasitic co-infections occurred more frequently in the most heavily infected livers.

Polygoni Multiflori Radix interferes with bile acid metabolism homeostasis by inhibiting Fxr transcription, leading to cholestasis.

Objective: To explore the possible mechanisms of cholestasis induced by Polygoni Multiflori Radix (PM). Methods: Low and high doses of water extract of PM were given to mice by gavage for 8weeks. The serum biochemical indexes of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyltransferase (GGT) alkaline phosphatase (ALP) and so on were detected in the second, fourth, sixth, and eighth weeks after administration. At the end of the eighth week of administration, the bile acid metabolic profiles of liver and bile were screened by high-performance liquid chromatography tandem triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS). Liver pathological changes were observed by hematoxylin and eosin staining. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA transcription of the target genes and Western blotting (WB) was used to the detect target protein expression. Results: Biochemical tests results showed the values of ALP and GGT were two and three times greater than the normal values respectively, and the value of R was less than 2. Histopathology also showed that PM caused lymphocyte infiltration, a small amount of hepatocyte necrosis and nuclear fragmentation in mouse liver. The proliferation of bile duct epithelial cells was observed in the high group. These results indicated that PM may lead to cholestatic liver injury. HPLC-QQQ-MS/MS analysis with the multivariate statistical analysis revealed significant alterations of individual bile acids in liver and gallbladder as compared to those of the control group. RT-qPCR showed that the transcription of Fxr, Shp, Bsep, Bacs, Mdr2, and Ugt1a1 were downregulated and that of Cyp7a1, Mrp3, and Cyp3a11 was significantly upregulated in the treatment group. WB demonstrated that PM also markedly downregulated the protein expression of FXR, BSEP, and MDR2, and upregulated CYP7A1. Conclusion: PM inhibited the expression of FXR, which reduced the expression of MDR2 and BSEP, leading to the obstruction of bile acids outflow, and increased the expression of CYP7A1, resulting in an increase of intrahepatic bile acid synthesis, which can lead to cholestasis.

Bone Marrow Mesenchymal Stem-Cell-Derived Exosomes Ameliorate Deoxynivalenol-Induced Mice Liver Damage.

Deoxynivalenol (DON) is a kind of Fusarium toxin that can cause a variety of toxic effects. DON is mainly metabolized and detoxified by the liver. When the concentration of DON exceeds the metabolic capacity of the liver, it will trigger acute or chronic damage to the liver tissue. Previous studies demonstrated that bone marrow mesenchymal stem-cell-secreted exosomes (BMSC-exos) reduce liver injury. Therefore, we issue a hypothesis that in vitro-cultured rat BMSC-secreted exos could ameliorate liver damage after 2 mg/kg bw/day of DON exposure. In total, 144 lipids were identified in BMEC-exos, including high polyunsaturated fatty acid (PUFA) levels. BMSC-exos treatment alleviated liver pathological changes and decreased levels of alanine aminotransferase, aspartate aminotransferase, inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and lipid peroxidation. Otherwise, low or high BMSC-exos treatment obviously changes DON-induced hepatic oxylipin patterns. According to the results from our correlation network analysis, Pearson correlation coefficient analysis, and hierarchical clustering analysis, the top 10% oxidized lipids can be classified into two categories: one that was positively correlated with copper-zinc superoxide dismutase (Cu/Zn SOD) and another that was positively correlated with liver injury indicators. Altogether, BMSC-exos administration maintained normal liver function and reduced oxidative damage in liver tissue. Moreover, it could also significantly change the oxylipin profiles under DON conditions.

Berberine Ameliorates Metabolic-Associated Fatty Liver Disease Mediated Metabolism Disorder and Redox Homeostasis by Upregulating Clock Genes: Clock and Bmal1 Expressions.

Metabolic-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases, which in turn triggers mild inflammation, metabolic dysfunction, fibrosis, and even cancer. Accumulating evidence has suggested that Berberine (BBR) could significantly improve MAFLD progression. Clock and Bmal1 as heterodimer proteins highly participated in the development of MAFLD, but whether BBR targets Clock and Bmal1 in MAFLD remains poorly understood. The result suggested that the protein levels of Clock and Bmal1 were decreased in MAFLD mice, which was negatively correlated with elevated reactive oxygen species (ROS) accumulation, the H2O2 level, liver inflammation, metabolic dysfunction, and insulin resistance. The mRNA and protein levels of Clock and Bmal1 were also decreased in glucosamine-induced HepG2 cells, which were are negatively related to glucose uptake, the ROS level, and the H2O2 level. More importantly, Bmal1 siRNA could mimic the effect of glucosamine in HepG2 cells. Interestingly, Berberine (BBR) could rescue metabolism disorder and redox homeostasis through enhancing Clock and Bmal1 expression in vivo and in vitro. Therefore, BBR might be an effective natural compound for alleviating redox homeostasis, metabolism disorder, and liver pathological changes in MAFLD by activating Clock and Bmal1 expression.