Liver asialoglycoprotein receptor levels correlate with severity of alcoholic liver damage in rats

It has been demonstrated that the oral administration of ethanol (Lieber-DeCarli liquid diet) to rats results in a decreased expression and content of the asialoglycoprotein receptor (ASGP-R) in the resultant fatty liver. In the present study, we wanted to determine whether the extent of impaired receptor content was correlated with the severity of liver pathology by using the intragastric feeding model. When ASGP-R protein and mRNA levels were measured in animals infused with ethanol or dextrose in the presence of fish oil (FO) or medium-chain triglyceride as the source of fat, more significant impairments to the ASGP-R were observed in the FO-ethanol group compared with the medium-chain triglyceride-ethanol group. Furthermore, only the FO-ethanol group showed pathological liver changes. These results demonstrate that a correlation exists between the progression of alcohol-associated liver injury, as defined by the severity of liver pathology, and an ethanol-induced decline in ASGP-R content.

Download Full-text

Total Parenteral Nutrition Induced Liver Pathology: An Autopsy Series of 24 Newborn Cases

Pediatric and Developmental Pathology ◽

10.1007/s10024-001-0154-7 ◽

2004 ◽

Vol 7 (5) ◽

pp. 425-432 ◽

Cited By ~ 96

Author(s):

Eduardo Zambrano ◽

Magdy El-Hennawy ◽

Richard A. Ehrenkranz ◽

Daniel Zelterman ◽

Miguel Reyes-Múgica

Keyword(s):

Birth Weight ◽

Liver Injury ◽

Parenteral Nutrition ◽

Total Parenteral Nutrition ◽

Liver Damage ◽

Gestational Age ◽

Liver Pathology ◽

Severe Liver ◽

Enteral Feedings ◽

Liver Changes

Total parenteral nutrition (TPN)-induced liver injury is a common complication in neonates managed with newborn intensive care. In several of these cases, irreversible and even fatal liver damage may develop, with patients dying of liver failure. In spite of multiple studies over several years, the pathogenesis of TPN-induced liver damage remains poorly understood. Clinical data from 24 neonates with clinical history of receiving TPN who died at Yale—New Haven Children's Hospital and had autopsies performed, were collected by medical record review without knowledge of liver pathology findings. Liver histological sections from these patients were evaluated for multiple parameters without knowledge of the clinical course. Continuous data were analyzed by Wilcoxon signed-rank test and Mann-Whitney test, and dichotomous data by Fisher's exact test; P < 0.05 was considered significant. Different histopathological abnormalities with varying degrees of severity were observed. A progression in the severity of histopathological changes in relation to duration of TPN administration (DTPN) was found. While patients with DTPN of < 2 wk had no fibrosis or only mild degrees of fibrosis, patients with more than 6 wk of DTPN developed moderate-to-severe fibrosis. Similar results were observed for cholestasis and bile duct proliferation. We did not find significant differences for birth weight, gestational age, occurrence of necrotizing enterocolitis, sepsis, or enteral feedings between the group with normal-to-mild liver changes (n = 16), and the group with moderate-to-severe liver changes (n = 8). On the other hand, DTPN was significantly different between these two groups (P = 0.008). Also, patients small for gestational age (P = 0.003) and patients with bronchopulmonary dysplasia (P = 0.001) were more commonly seen in the group with moderate-to-severe histopathological findings. Intracellular copper was detected in 12.5% of patients with moderate-to-severe liver changes, and was found in 50% of patients with normal-to-mild liver findings (P = 0.04). Detection of copper from tissue sections also decreased with DTPN, being observed in 57% of patients with < 2 wk DTPN and in none of the patients with > 12 wk DTPN. Our findings confirm the known significant relationship between the duration of TPN and liver injury. While previously described associations with birth weight, gestational age, enteral feedings, necrotizing enterocolitis, and sepsis were not noted, our study suggests that poor intrauterine growth may be a significant clinical risk factor for TPN-induced liver injury. In addition, our findings suggest that copper may have a protective effect against the development of TPN-induced liver damage.

Download Full-text

Curcumin Decreased Oxidative Stress, Inhibited NF-κB Activation, and Improved Liver Pathology in Ethanol-Induced Liver Injury in Rats

Journal of Biomedicine and Biotechnology ◽

10.1155/2009/981963 ◽

2009 ◽

Vol 2009 ◽

pp. 1-8 ◽

Cited By ~ 55

Author(s):

Suchittra Samuhasaneeto ◽

Duangporn Thong-Ngam ◽

Onanong Kulaputana ◽

Doungsamon Suyasunanont ◽

Naruemon Klaikeaw

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Early Stage ◽

Control Group ◽

Liver Pathology ◽

Sprague Dawley ◽

Hepatocyte Apoptosis ◽

Sod Activity ◽

Ethanol Group ◽

Liver Histopathology

To study the mechanism of curcumin-attenuated inflammation and liver pathology in early stage of alcoholic liver disease, female Sprague-Dawley rats were divided into four groups and treated with ethanol or curcumin via an intragastric tube for 4 weeks. A control group treated with distilled water, and an ethanol group was treated with ethanol (7.5 g/kg bw). Treatment groups were fed with ethanol supplemented with curcumin (400 or 1 200 mg/kg bw). The liver histopathology in ethanol group revealed mild-to-moderate steatosis and mild necroinflammation. Hepatic MDA, hepatocyte apoptosis, and NF-κB activation increased significantly in ethanol-treated group when compared with control. Curcumin treatments resulted in improving of liver pathology, decreasing the elevation of hepatic MDA, and inhibition of NF-κB activation. The 400 mg/kg bw of curcumin treatment revealed only a trend of decreased hepatocyte apoptosis. However, the results of SOD activity, PPARγprotein expression showed no difference among the groups. In conclusion, curcumin improved liver histopathology in early stage of ethanol-induced liver injury by reduction of oxidative stress and inhibition of NF-κB activation.

Download Full-text

Susceptibility of Asialoglycoprotein Receptor-Deficient Mice to Lps/Galactosamine Liver Injury and Protection by Betaine Administration

Biology ◽

10.3390/biology10010019 ◽

2020 ◽

Vol 10 (1) ◽

pp. 19

Author(s):

Karuna Rasineni ◽

Serene M. L. Lee ◽

Benita L. McVicker ◽

Natalia A. Osna ◽

Carol A. Casey ◽

...

Keyword(s):

Liver Injury ◽

Liver Failure ◽

Liver Damage ◽

Asialoglycoprotein Receptor ◽

Fulminant Liver Failure ◽

Wild Type ◽

Tissue Samples ◽

Tnf Α ◽

Deficient Mice

Background: Work from our laboratory has shown that the ethanol-induced increase in apoptotic hepatocellular death is closely related to the impairment in the ability of the asialoglycoprotein receptor (ASGP-R) to remove neighboring apoptotic cells. In this study, we assessed the role of ASGP-R in fulminant liver failure and investigated whether prior treatment with betaine (a naturally occurring tertiary amine) is protective. Methods: Lipopolysaccharide (LPS; 50 μg/kg BW) and galactosamine (GalN; 350 mg/kg BW) were injected together to wild-type and ASGP-R-deficient mice that were treated for two weeks prior with or without 2% betaine in drinking water. The mice were sacrificed 1.5, 3, or 4.5 h post-injection, and tissue samples were collected. Results: LPS/GalN injection generate distinct molecular processes, which includes increased production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), thus causing apoptosis as evident by increased caspase-3 activity. ASGP-R deficient animals showed increased liver caspase activities, serum TNF-α and IL-6 levels, as well as more pronounced liver damage compared with the wild-type control animals after intraperitoneal injection of LPS/GalN. In addition, prior administration of betaine was found to significantly attenuate the LPS/GalN-induced increases in liver injury parameters. Conclusion: Our work underscores the importance of normal functioning of ASGP-R in preventing severe liver damage and signifies a therapeutic role of betaine in prevention of liver injuries from toxin-induced fulminant liver failure.

Download Full-text

Drug delivery system. Oral administration of BRM (OK-432 medium chain triglyceride emulsion) and inhibition of hepatic metastasis.

Drug Delivery System ◽

10.2745/dds.4.276 ◽

1989 ◽

Vol 4 (4) ◽

pp. 276-280

Author(s):

Masao Fujimaki ◽

Tokuzo Kasagi ◽

Kenji Tazawa ◽

Masatoshi Maeda ◽

Takashi Honda

Keyword(s):

Drug Delivery ◽

Oral Administration ◽

Drug Delivery System ◽

Delivery System ◽

Hepatic Metastasis ◽

Medium Chain Triglyceride ◽

Medium Chain

Download Full-text

The Potential Hepatoprotective and Antioxidant Activities of Astragalus davisii against Paracetamol Induced Liver Damage in Rats

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2020/v32i2330797 ◽

2020 ◽

pp. 102-114

Author(s):

Ahmed I. Foudah ◽

Mohammed H. Alqarni ◽

Gamal A. Soliman ◽

Rehab F. Abdel- Rahman ◽

Özgen Alankuş- Çalışkan ◽

...

Keyword(s):

Liver Injury ◽

Oral Administration ◽

Liver Damage ◽

Antioxidant Activities ◽

Radical Scavenging ◽

Antioxidant Effect ◽

Dpph Radical ◽

Glutamyl Transferase ◽

Dpph Radical Scavenging

The current study aimed to estimate in vitro antioxidant effect of Astragalus davisii (A. davisii) extract. Further, the possible protective effect of A. davisii against paracetamol (PCM)-induced liver injury was assessed in rats. A. davisii was tested for its antioxidant activity using DPPH radical scavenging assay. The hepatoprotective potential of the extract was assessed in rats following oral administration for 7 days. Liver injury was induced in rats following oral administration of PCM overdose. Hepatic biomarkers; alanine-aminotransferase, aspartate-aminotransferase, alkaline-phosphatase, γ-glutamyl transferase and bilirubin were increased, while total protein and albumin were reduced in PCM control animals. Additionally, the activities of superoxide dismutase (SOD), catalase and glutathione-peroxidase (GPx) and the levels of glutathione were significantly declined, while levels of hepatic malondialdehyde (MDA) were significantly elevated in PCM alone treated rats. Oral administration of A. davisii (400 mg/kg) prior to PCM inhibited the elevation in the levels of liver damage markers in serum and protected against oxidative stress. Histopathological remarks confirmed the hepatoprotective potential of the extract. The results suggest that A. davisii extract at 400 mg/kg protects liver against injury induced by PCM overdose.

Download Full-text

Differential Effects of Fatty Acid Saturation and Chain Length on NASH in Juvenile Iberian Pigs

Current Developments in Nutrition ◽

10.1093/cdn/nzaa050_005 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 682-682 ◽

Cited By ~ 1

Author(s):

Kayla Dillard ◽

Morgan Coffin ◽

Gabriella Hernandez ◽

Victoria Smith ◽

Catherine Johnson ◽

...

Keyword(s):

Fatty Acids ◽

Body Weight ◽

Fatty Acid ◽

Liver Injury ◽

Olive Oil ◽

Coconut Oil ◽

Long Chain Fatty Acids ◽

Medium Chain ◽

Long Chain ◽

Chain Fatty Acids

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) represents the major cause of pediatric chronic liver pathology in the United States. The objective of this study was to compare the relative effect of inclusion of isocaloric amounts of saturated medium-chain fatty acids (hydrogenated coconut oil), saturated long-chain fatty acids (lard) and unsaturated long-chain fatty acids (olive oil) on endpoints of NAFLD and insulin resistance. Methods Thirty-eight 15-d-old Iberian pigs were fed 1 of 4 diets containing (g/kg body weight × d) 1) control (CON; n = 8): 0 g fructose, 10.5 g fat, and 187 kcal metabolizable energy (ME), 2) lard (LAR; n = 10): 21.6 g fructose, 17.1 g fat (100% lard) and 299 kcal ME, 3) hydrogenated coconut oil (COCO; n = 10): 21.6 g fructose, 16.9 g fat (42.5% lard and 57.5% coconut oil) and 299 kcal ME, and 4) olive oil (OLV, n = 10): 21.6 g fructose, 17.1 g fat (43.5% lard and 56.5% olive oil) and 299 kcal ME, for 9 consecutive weeks. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 60 at 2 h post feeding, with all other serum measures assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and metabolomics analysis. Results Tissue histology indicated the presence of steatosis in LAR, COCO and OLV compared with CON (P ≤ 0.001), with a further increase in in non-alcoholic steatohepatitis (NASH) in OLV and COCO compared with LAR (P ≤ 0.01). Alanine and aspartate aminotransferases were higher in COCO and OLV (P ≤ 0.01) than CON. All treatment groups had lower liver concentrations of methyl donor's choline and betaine versus CON, while bile acids were differentially changed (P ≤ 0.05). COCO had higher levels of TGs with less carbons (Total carbons < 52) than all other groups (P ≤ 0.05). Several long-chain acylcarnitines involved in fat oxidation were higher in OLV versus all other groups (P ≤ 0.05). Conclusions Inclusion of fats enriched in medium-chain saturated and long-chain unsaturated fatty acids in a high-fructose high-fat diet increased liver injury, compared with fats with a long-chain saturated fatty acid profile. Further research is required to investigate the mechanisms causing this difference in physiological response to these dietary fat sources. Funding Sources ARI, AcornSeekers.

Download Full-text

Stabilisation of Lutein and Lutein Esters with Polyoxyethylene Sorbitan Monooleate, Medium-Chain Triglyceride Oil and Lecithin

Foods ◽

10.3390/foods10030500 ◽

2021 ◽

Vol 10 (3) ◽

pp. 500

Author(s):

Zala Gombač ◽

Ilja Gasan Osojnik Črnivec ◽

Mihaela Skrt ◽

Katja Istenič ◽

Andreja Knez Knafelj ◽

...

Keyword(s):

Aqueous Solutions ◽

Medium Chain Triglyceride ◽

Storage Conditions ◽

Sorbitan Monooleate ◽

Medium Chain ◽

Poorly Soluble

Lutein is a challenging compound to incorporate into food, as it is poorly soluble and unstable in aqueous solutions. In this study, the aim was to prepare stable encapsulates of lutein and lutein esters using feasible and straightforward techniques. Fine suspensions based on polyoxyethylene sorbitan monooleate and medium-chain triglyceride oil micelle-like units with 3.45% lutein esters or 1.9% lutein equivalents provided high encapsulation efficiencies of 79% and 83%, respectively. Lutein encapsulated in fine suspensions showed superior stability, as 86% was retained within the formulation over 250 days at 25 °C in the dark. Under the same storage conditions, only 38% of lutein remained in corresponding formulations. Higher encapsulation efficiencies were achieved with lecithin emulsions, at up to 99.3% for formulations with lutein, and up to 91.4% with lutein esters. In lecithin emulsions that were stored for 250 days, 17% and 80% of lutein and lutein esters, respectively, were retained within the formulations.

Download Full-text

Creatine Alleviates Doxorubicin-Induced Liver Damage by Inhibiting Liver Fibrosis, Inflammation, Oxidative Stress, and Cellular Senescence

Nutrients ◽

10.3390/nu13010041 ◽

2020 ◽

Vol 13 (1) ◽

pp. 41

Author(s):

Nouf Aljobaily ◽

Michael J. Viereckl ◽

David S. Hydock ◽

Hend Aljobaily ◽

Tsung-Yen Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Methylation ◽

Body Weight ◽

Liver Fibrosis ◽

Liver Damage ◽

Cellular Senescence ◽

Weight Ratio ◽

Mrna Levels ◽

Body Weight Ratio ◽

Chromosomal Stability

Background: Treatment with the chemotherapy drug doxorubicin (DOX) may lead to toxicities that affect non-cancer cells including the liver. Supplementing the diet with creatine (Cr) has been suggested as a potential intervention to minimize DOX-induced side effects, but its effect in alleviating DOX-induced hepatoxicity is currently unknown. Therefore, we aimed to examine the effects of Cr supplementation on DOX-induced liver damage. Methods: Male Sprague-Dawley rats were fed a diet supplemented with 2% Cr for four weeks, 4% Cr for one week followed by 2% Cr for three more weeks, or control diet for four weeks. Animals then received either a bolus i.p. injection of DOX (15 mg/kg) or saline as a placebo. Animals were then sacrificed five days-post injection and markers of hepatoxicity were analyzed using the liver-to-body weight ratio, aspartate transaminase (AST)-to- alanine aminotransferase (ALT) ratio, alkaline phosphatase (ALP), lipemia, and T-Bilirubin. In addition, hematoxylin and eosin (H&E) staining, Picro-Sirius Red staining, and immunofluorescence staining for CD45, 8-OHdG, and β-galactosidase were performed to evaluate liver morphology, fibrosis, inflammation, oxidative stress, and cellular senescence, respectively. The mRNA levels for biomarkers of liver fibrosis, inflammation, oxidative stress, and senescence-related genes were measured in liver tissues. Chromosomal stability was evaluated using global DNA methylation ELISA. Results: The ALT/AST ratio and liver to body weight ratio tended to increase in the DOX group, and Cr supplementation tended to attenuate this increase. Furthermore, elevated levels of liver fibrosis, inflammation, oxidative stress, and senescence were observed with DOX treatment, and Cr supplementation prior to DOX treatment ameliorated this hepatoxicity. Moreover, DOX treatment resulted in chromosomal instability (i.e., altered DNA methylation profile), and Cr supplementation showed a tendency to restore chromosomal stability with DOX treatment. Conclusion: The data suggest that Cr protected against DOX-induced hepatotoxicity by attenuating fibrosis, inflammation, oxidative stress, and senescence.

Download Full-text

Lemon Balm and Dandelion Leaf Extracts Synergistically Protect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Applied Sciences ◽

10.3390/app11010390 ◽

2021 ◽

Vol 11 (1) ◽

pp. 390

Author(s):

Beom-Rak Choi ◽

Il-Je Cho ◽

Su-Jin Jung ◽

Jae-Kwang Kim ◽

Dae-Geon Lee ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Acute Liver Injury ◽

Antioxidant Activities ◽

Body Weight Gain ◽

Histopathological Analysis ◽

Related Factor ◽

Mrna Levels ◽

Protective Effects ◽

Lemon Balm

Lemon balm and dandelion are commonly used medicinal herbs exhibiting numerous pharmacological activities that are beneficial for human health. In this study, we explored the protective effects of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (MLD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. CCl4 (0.5 mL/kg; i.p.) injection inhibited body weight gain and increased relative liver weight. Pre-administration of MLD (50–200 mg/kg) for 7 days prevented these CCl4-mediated changes. In addition, histopathological analysis revealed that MLD synergistically alleviated CCl4-mediated hepatocyte degeneration and infiltration of inflammatory cells. MLD decreased serum aspartate aminotransferase and alanine transferase activities and reduced the number of liver cells that stained positive for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting that MLD protects against CCl4-induced hepatic damage via the inhibition of apoptosis. Moreover, MLD attenuated CCl4-mediated lipid peroxidation and protein nitrosylation by restoring impaired hepatic nuclear factor erythroid 2-related factor 2 mRNA levels and its dependent antioxidant activities. Furthermore, MLD synergistically decreased mRNA and protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the liver. Together, these results suggest that MLD has potential for preventing acute liver injury by inhibiting apoptosis, oxidative stress, and inflammation.

Download Full-text

Isolation, Identification and Function of Pichia anomala AR2016 and Its Effects on the Growth and Health of Weaned Pigs

Animals ◽

10.3390/ani11041179 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1179

Author(s):

Yajun Ma ◽

Zhihong Sun ◽

Yan Zeng ◽

Ping Hu ◽

Weizhong Sun ◽

...

Keyword(s):

Oral Administration ◽

Relative Abundance ◽

Bile Salts ◽

Average Daily Gain ◽

Pichia Anomala ◽

Simulated Gastric Fluid ◽

Transferase Activity ◽

Mrna Levels ◽

Weaned Pigs ◽

Intestinal Juice

This study isolates and identifies Pichia anomala (P. anomala) AR2016, and studies its effect on the growth and health of weaned pigs. A P. anomala strain from solid wine koji is isolated and identified using 26S rDNA analysis, and its culture conditions are optimized. Heat tolerance, bile salt tolerance, artificial gastric, and intestinal juice tolerance are evaluated. In our methodology, thirty 28 d Large White × Landrace × Rongchang weaned pigs were randomly divided into three groups with 10 barrows in each, and fed a maize-soybean meal diet and orally administered 0.85% saline (CK), 1 mL 1 × 109 cfu/mL Candida utilis (C. utilis), and 1 mL 1 × 109 cfu/mL P. anomala once daily for 28 days. A P. anomala strain was identified and named P. anomala AR2016. P. anomala AR2016 grew best in yeast extract peptone dextrose medium with pH 5.0 at 28 °C, 180 r/min and could tolerate 45 °C for 0.5 h, 0.2% pig bile salts, simulated gastric fluid, and 1.0% simulated intestinal fluid. Our results show that compared with the CK group, orally administered P. anomala AR2016 increases average daily gain, the ileal villus height, the ileal mucosal concentrations of occludin and zonula occluens-1, the serum glucose and total protein concentration, total superoxide dismutase, glutathione peroxidase, and total antioxidative capacity activity, the trypsin and lipase activity in jejunal and ileal contents, the jejunal and ileal mucosa mRNA levels of ALP, TNF-α, and TLR-2, and the relative abundance of Bacteroidetes, Actinobacteria, Succinivibrionaceae, Lachnospiraceae, and Prevotellaceae (p < 0.05). Compared with the CK group, oral administration of P. anomala AR2016 decreased the incidence of diarrhea, aspartate aminotransferase activity, alanine amino-transferase-activity, malondialdehyde, D-lactic acid and endotoxin content in serum, the mRNA level of aminopeptidase N of ileum mucosa, and the relative abundance of Proteobacteria, Clostridiaceae, Campylobacteraceae, Vibrionaceae, Bacillus, and Pseudon (p < 0.05). Collectively, the study indicates that P. anomala AR2016 can tolerate high acidity and high bile salts, and has high survivability in the artificial gastric intestinal juice environment. Oral administration of P. anomala AR2016 improves the growth performance, reduces the incidence of diarrhea, enhances intestinal barrier function, and improves microflora in weaned pigs.

Download Full-text