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Drug-induced liver injury (DILI) is a serious adverse hepatic event presenting diagnostic and prognostic challenges. The clinical categorization of DILI into hepatocellular, cholestatic, or mixed phenotype is based on serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values; however, this classification may not capture the full spectrum of DILI subtypes. With this aim, we explored the utility of assessing changes in the plasma metabolomic profiles of 79 DILI patients assessed by the RUCAM (Roussel Uclaf Causality Assessment Method) score to better characterize this condition and compare results obtained with the standard clinical characterization. Through the identification of various metabolites in the plasma (including free and conjugated bile acids and glycerophospholipids), and the integration of this information into predictive models, we were able to evaluate the extent of the hepatocellular or cholestatic phenotype and to assign a numeric value with the contribution of each specific DILI sub-phenotype into the patient's general condition. Additionally, our results showed that metabolomic analysis enabled the monitoring of DILI variability responses to the same drug, the transitions between sub-phenotypes during disease progression, and identified a spectrum of residual DILI metabolic features, which can be overlooked using standard clinical diagnosis during patient follow-up. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has led to a global health crisis. The virus can cause varying severity of liver injury, but the mechanism has not yet been elucidated, especially in pregnancy.

There are three homologous proteins (α, β and γ) in the growth arrest and DNA damage 45 (Gadd45) family. These proteins act as cellular responders to physiological and environmental stimuli. Gadd45β plays a significant role in the pathogenesis of liver diseases. Liver injury and growth stimulation increase expression of Gadd45β, which promotes cell survival, growth and proliferation in normal liver cells. By contrast, Gadd45β plays a role in promoting apoptosis and inhibiting tumour function in hepatocellular carcinoma (HCC). Currently, it is believed that Gadd45β benefits the liver through two different pathways: binding to MAPK kinase 6 (MKK6) to increase PCD induced by p38 (inhibiting tumours) or binding to constitutive androstane receptor (CAR) to jointly activate transcription of liver synthesis metabolism (promoting liver regeneration). This article aims to systematically review the role of Gadd45β in liver diseases, including its regulatory mechanism on expression and involvement in liver cell damage, inflammation, fibrosis and HCC. In conclusion, we explore the potential of targeting Gadd45β as a therapeutic strategy for liver diseases., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

In the present socioeconomic era, people are consuming ready‐made fast‐food regularly with minimal physical exercise. Food processors use monosodium glutamate, saturated fatty acids, and hydrogenated fats to prepare flavor‐enhancing high‐lipid diet (FHD), which cause oxidative damage to different experimental animals and humans through the generation of reactive oxygen species. This study aimed to assess the protective effects of Coccinia grandis against hepatocellular damage caused by FHD. Rats were fed with FHD (prepared with monosodium glutamate in combination with HLD) with or without ethanol extract of Coccinia grandis leaves (EECGL) for 28 days to measure hematological, biochemical, inflammatory, apoptotic biomarkers, cytomorphological changes, and apoptosis of liver, if any. The results indicate that FHD causes hepatic damage by modifying hematological and biochemical parameters, followed by the activation of NF‐kB and caspase pathways. Moreover, FHD altered the Bcl2/Bax ratio, nuclear condensation, shrinkage, and fragmentation of hepatocytes, leading to inflammation and apoptosis. On the other hand, EECGL appears to play a significant role in preventing FHD‐induced hepatocellular damage via regulating inflammatory and apoptotic factors. In this regard, EECGL might be a useful dietary supplement to reduce the negative impact of a frequent consumption of FHD as part of fast‐food. Practical applications: Fast food is believed to be a flavor‐enhanced high‐lipid diet, since its delectable taste stimulates the hunger. Eventually, such a diet functions as a silent assassin for many body systems. The current study primarily focused on the negative health effects of commonly used flavoring agents in high‐lipid diets, which presents a warning against the choice of meals, particularly food additive mixed diets, and issues an alarming signal to society concerning the use of such combinations in regular diets. Furthermore, this study recommends using Coccinia grandis, which has a variety of bioactive phytoconstituents, as a dietary supplement to counteract the flavor‐enhancing high‐lipid diet‐induced anomalous condition. [ABSTRACT FROM AUTHOR]

Abstract Background Jatropha tanjorensis is a commonly consumed green leafy plant that has found usage in folk medicine. Sodium benzoate (C6H5COONa) is a widely used preservative in food/drink industries with potential cytotoxicity. Protective effect of some leafy plants on xenobiotic-induced toxicity have been established. Hence, this study sought to investigate the protective effect of methanolic leaf extract of Jatropha tanjorensis on sodium benzoate mediated renal and hepatic dysfunction in rats. Results Sodium benzoate treatment caused significant (P

Acute liver failure (ALF) exemplifies a rapid decline in liver function among individuals with previously healthy livers, often manifesting through symptoms such as jaundice, confusion, and potentially life-threatening complications. Timely medical intervention, and, in severe instances, liver transplantation, are essential for enhancing outcomes and averting further deterioration. While the causes of ALF are multifaceted, in developed nations, it predominantly arises from drug-induced liver injury. Treatment primarily revolves around supportive measures, with severe cases necessitating liver transplantation. In instances where acute overdose with acetaminophen serves as the instigating factor, N-acetylcysteine (NAC) emerges as a pivotal component of management, as indicated by the Rumack-Matthew nomogram. The Rumack-Matthew nomogram guides treatment for acetaminophen overdose by correlating serum levels with the risk of liver damage. If levels exceed a set threshold, NAC is administered to prevent toxicity by replenishing glutathione. The decision to administer NAC is typically guided by this clinical tool, which aids healthcare providers in determining the appropriate course of action. NAC assumes a critical role in ameliorating the detrimental effects of acetaminophen overdose, particularly in averting liver damage, thus holding significant importance in patient care and recovery. While chronic acetaminophen overdose cases leading to ALF may also benefit from NAC, the supporting evidence remains weak. In this context, we present a case of ALF stemming from chronic acetaminophen ingestion, managed with NAC when liver transplantation was not a viable option., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Shah et al.)

Aim: Presently, no standardized definition or acceptable diagnostic criteria have been established for acute presentation of autoimmune hepatitis (AP‐AIH), making it difficult to differentiate that condition from drug‐induced liver injury (DILI). This study aimed to characterize clinical and histological features for distinguishing between AP‐AIH and DILI. Methods: Clinical, biochemical, and histological characteristics of AP‐AIH and DILI in clinically well‐characterized cases were compared in a standardized manner to clarify differences. Results: In clinical evaluations, immunoglobulin G level and rate of anti‐nuclear antibody positivity were greater in AP‐AIH than DILI cases. As for diagnosis of each condition, significant (P < 0.01) differences were found for 10 features: lobular necrosis/inflammation, cobblestone appearance of hepatocytes, plasma cell infiltration in liver parenchyma, centrilobular fibrosis, hepatic rosette formation in areas with cobblestone appearance, portal inflammation, interface hepatitis, prominent plasma cells in portal areas, bile duct injury, and hepatic rosette formation in periportal areas. The area under the curve and cut‐off values for the combination of these 10 features were 0.95 and 9 (sensitivity 86%, specificity 90%), respectively. Conclusion: Combinations of histological features were found to be helpful for differentiating AP‐AIH from DILI, but we were not able to statistically identify an individual feature as definitive. [ABSTRACT FROM AUTHOR]

Background: Jatropha tanjorensis is a commonly consumed green leafy plant that has found usage in folk medicine. Sodium benzoate (C6H5COONa) is a widely used preservative in food/drink industries with potential cytotoxicity. Protective effect of some leafy plants on xenobiotic-induced toxicity have been established. Hence, this study sought to investigate the protective effect of methanolic leaf extract of Jatropha tanjorensis on sodium benzoate mediated renal and hepatic dysfunction in rats. Results: Sodium benzoate treatment caused significant (P < 0.05) alteration in kidney (serum urea, uric acid, and creatinine) and liver (aspartate and alanine transaminases, acid and alkaline phosphatases) damage markers, serum albumin, globulin and total protein levels as well as cellular architecture which were significantly reversed in groups treated with the leaf extracts. Phytochemical screening of the leaf extract revealed the presence of terpenoids, saponins, cardiac glycosides, flavonoids and tannins. Conclusion: Sodium benzoate-induced alterations in the renal and hepatic indices were mitigated following treatment with J. tanjorensis leaf extracts which suggests protective effect of the extract against sodium benzoate intoxication. [ABSTRACT FROM AUTHOR]

Bromodeoxyuridine (BrdU) is used in studies related to cell proliferation and neurogenesis. The multiple intraperitoneal injections of this molecule could favor liver function profile changes. In this study, we evaluate the systemic and hepatocellular impact of BrdU in male adult Wistar rats in 30 %-partial hepatectomy (PHx) model. The rats received BrdU 50 mg/Kg by intraperitoneal injection at 0.5, 1, 2, 3, 6, 9 and 16 days after 30 %-PH. The rats were distributed into four groups as follows, control, sham, PHx/BrdU(-) and PHx/BrdU(+). On day 16, we evaluated hepatocellular nuclei and analyzed histopathological features by haematoxylin-eosin stain and apoptotic profile was qualified by caspase-3 presence. The systemic effect was evaluated by liver markers such as alanine transferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (AP), bilirubin, total proteins and serum albumin content. The statistical analysis consisted of a student t-test and one-way ANOVA. BrdU did not induce apoptosis or hepatocellular damage in male rats. Multiple administrations of BrdU in male rats did not induce significant decrease body weight, but increased serum ALT and LDH levels were found. Our results show that the BrdU does not produce hepatocellular damage. [ABSTRACT FROM AUTHOR]

One of the major hazards arising from recycling sites is the generation of leachate containing mixed metal. This study evaluated the toxic effects of leachate obtained from Elewi Odo municipal auto-battery recycling site (EOMABRSL) on male liver functions using hepatic indices and biomarker of cellular adenosine triphosphate (ATP) in rat via the oral route. Concentrations of heavy metals analysis showed that lead, cadmium, nickel, chromium, manganese, and iron were 1.5-, 2-, 2.5-, 1.36-, 19.61-, and 8.89-folds, respectively, higher than acceptable limits set by regulatory authority World Health Organization. Copper, zinc, and cobalt were 5.9-, 300-, and 1.02-folds, respectively, lower than permissible limits. The EOMABRSL was administered at 20, 40, 60, 80, and 100% concentrations to adult male rats for 60 days. Following exposure, plasma and livers were collected for several biochemistry assays. Exposure of animals to EOMABRSL resulted in 27.51, 28.14, 63.93, 28.42, and 40.16% increase in aspartate aminotransferase activity, whereas it elevated alanine aminotransferase activity by 5.35, 22.33, 88.68, 183.02, and 193.08%, respectively, when compared with the control. Similarly, γ-glutamyl transferase activity increased by 111.22, 114.19, 122.96, 573.14, and 437.02%, respectively, when compared with the control. EOMABRSL administration significantly decreased catalase activity and reduced glutathione level and superoxide dismutase with concomitant increase in malondialdehyde and hydrogen peroxide levels. Also, significant (p < 0.05) decrease in lactate dehydrogenase (LDH) activity (marker of cellular ATP) was observed. Taken together, the hepatotoxicity of EOMABRSL could be due to the depletion of LDH and induction of oxidative damage, which may suggest possible health hazards in subjects with occupational or environmental exposure. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Polygoni Multiflori Radix (PMR) has been traditionally used as a tonic and an anti-aging remedy for centuries; however, hepatic lesions linked to PMR have been frequently reported. Aim of the study This work attempted to investigate the hepatotoxic potential of PMR extract and the toxicokinetics of stilbene glucoside and anthraquinones in PMR extract following repeated administration. Materials and methods Histopathological and biochemical tests were performed to assess the hepatotoxicity of PMR extract. A rapid and sensitive liquid chromatography–mass spectrometry (LC–MS) assay was developed for toxicokinetic analysis of the main constituents of PMR extract, including 2,3,5,4′-tetrahydroxystilbene-2- O - β - d -glucoside (TSG), emodin-8- O - β - d -glucoside and emodin. Results The histopathological and biochemical tests indicated that repeated administration of high-dose PMR extract (20 g/kg) for 3 weeks could cause hepatic lesions, while the low-dose treatment (1 g/kg) was safe. Necrosis and steatosis of hepatic cells, inflammatory cell infiltration and mild fibrosis were the main toxicity symptoms caused by high-dose PMR extract in rat liver. The aspartate aminotransferase (AST) levels increased by approximately 17%, from 110.80±0.84 to 129.75±10.83 IU/L, in the high-dose group compared with the control group. The proposed LC–MS method was proven to be suitable for the simultaneous quantification of these three constituents by affording desirable linearity ( r 2 >0.998) and satisfactory precision (error less than 10%). The toxicokinetic study showed that emodin could not be detected in the low-dose group, but the AUC and C max of emodin displayed a gradual increase with repeated treatments in the high-dose group. The toxicokinetics of TSG in the low- and high-dose groups exhibited similar trends after repeated administration. Conclusions Consideration needs to be given to the rational application of PMR in the clinic to balance its benefits and risks. The increased emodin exposure in vivo provided a putative explanation for the observed hepatic lesions induced by PMR extract, although further studies to confirm the potentially causal link between emodin exposure and hepatic lesions are still necessary. [ABSTRACT FROM AUTHOR]

This study was designed to find out the efficacy of ethanol extracts of Punica granatum peel and Vitis vinifera seeds on diethylnitrosamine (DEN)-induced oxidative stress and hepatocellular damage in Wistar rats. Rats were divided into four groups. The first group served as normal control, and the second group received DEN at a dose of 200 mg/kg body weight by single intraperitoneal administration. The third one received DEN as in DEN-treated group and co-treated with 400 mg/kg P. granatum peel extract. The final group also received DEN and co-treated with 400 mg/kg V. vinifera seed extract. DEN administration to rats resulted in significantly elevated levels of serum SGPT, SGOT, ALP, and GGT which is indicative of hepatocellular damage. DEN-induced oxidative stress was confirmed by elevated levels of lipid peroxides and decreased activities of superoxide dismutase, catalase, and glutathione peroxidase in the serum and liver tissues. The status of non-enzymatic antioxidants like vitamin C, vitamin E, and reduced glutathione were also found to be decreased in serum and tissues of DEN-administered rats. Co-treatment with the P. granatum peel and V. vinifera seed extracts orally for 12 weeks significantly reversed the DEN-induced alterations in the serum and liver tissues. [ABSTRACT FROM AUTHOR]

Quantitative trait locus (QTL) mapping is a powerful method to find modifier loci that influence disease risk and progression without prior knowledge of underlying genetic mechanisms. The aim of this study is to identify gene loci that contribute to individual differences in liver fibrosis following chronic liver damage. For this purpose, we carried out a mapping study across a panel of 21 BXD recombinant inbred strains using primary hepatocytes challenged with transforming growth factor (TGF)-β for 48 h. We identified a 6 Mb interval on chromosome 11 that is a major modifier of TGF-β-induced hepatocyte injury. Corresponding in vivo genetic analysis of fibrosis after chronic hepatotoxic injury by carbon tetrachloride (CCl4 ip for 6 wk) highlighted the same locus. Expression QTL (eQTL) analysis in liver tissues in the BXD family identified six polymorphisms in this region that are associated with strong cis eQTLs and that correlate well with gene expression in liver after both 6 wk CCl4 treatment and acute ethanol damage of the liver. Within this interval we rank two genes containing coding sequence variants as strong candidates that may modulate the severity of liver fibrosis: 1) the extracellular proteinase inhibitor gene Expi (also known as Wdnm1 or Wfdc18) and 2) musashi RNA-binding protein 2 (Msi2). The powerful combination of experimental, genetics, and bioinformatics methods, as well as combined in vitro and in vivo approaches can be used to define QTLs, genes, and even candidate sequence variants linked to hepatotoxicity and fibrosis. [ABSTRACT FROM AUTHOR]

Background Manipulation of the liver during liver surgery results in profound hepatocellular damage. Experimental data show that mobilization-induced hepatocellular damage is related to hepatic inflammation. To date, information on this link in humans is lacking. As it is possible to modulate inflammation, it is clinically relevant to unravel this relationship. Aim This observational study aimed to establish the association between liver mobilization and hepatic inflammation in humans. Methods Consecutive patients requiring mobilization of the right hemi-liver during liver surgery were studied. Plasma samples and liver biopsies were collected prior to and directly after mobilization and after transection of the liver. Hepatocellular damage was assayed by liver fatty acid-binding protein (L- FABP) and aminotransferase levels. Hepatic inflammation was determined by (a) immunohistochemical identification of myeloperoxidase ( MPO) and CD68- positive cells and (b) hepatic gene expression of inflammatory and cell adhesion molecules ( IL-1β, IL-6, IL-8, VCAM-1 and ICAM-1). Results A total of 25 patients were included. L-FABP levels increased significantly during mobilization (301 ± 94 ng/ml to 1599 ± 362 ng/ml, P = 0.008), as did ALAT levels (36 ± 5 IU/L to 167 ± 21 IU/L, P < 0.001). A significant increase in MPO ( P = 0.001) and CD68 ( P = 0.002) positive cells was noticed in the liver after mobilization. The number of MPO-positive cells correlated with the duration of mobilization (Pearson correlation=0.505, P = 0.033). Hepatic gene expression of pro-inflammatory cytokines IL-1β and IL-6, chemo-attractant IL-8 and adhesion molecule ICAM-1 increased significantly during liver manipulation. Conclusions Liver mobilization is associated with hepatocellular damage and liver inflammation, as shown by infiltration of inflammatory cells and upregulation of genes involved in acute inflammation. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder including simple steatosis and nonalcoholic steatohepatitis (NASH). Advanced stages of NASH result ultimately in fibrosis, cirrhosis, and hepatocarcinoma. A diagnosis of NASH entails an increased risk of both liver-related and cardiovascular mortality as worsening of the metabolic syndrome. Because of its escalation, many investigations have been performed to elucidate the pathophysiologic origins of the disease progression. Human epidemiologic studies describing polymorphisms in a number of genes involved in metabolic dysfunctions have contributed to clarify the causes leading to the disease evolution. In this review, we attempt to outline critically the most recently identified genetic variants in NAFLD patients to identify possible risk factors promoting the progression of the disease. The evaluation of altered genotypes together with other clinical variables may facilitate the clinical management of these patients. [ABSTRACT FROM AUTHOR]

Background & Aims: Aminotransferases are commonly used to determine the optimal duration of ischemic intervals during intermittent Pringle maneuver (IPM). However, they might not be responsive enough to detect small differences in hepatocellular damage. Liver fatty acid-binding protein (L-FABP) has been suggested as a more sensitive marker. This randomized trial aimed to compare hepatocellular injury reflected by L-FABP in patients undergoing liver resection with IPM using 15 or 30min ischemic intervals. Methods: Twenty patients undergoing liver surgery were randomly assigned to IPM with 15 (15IPM) or 30 (30IPM) minutes ischemic intervals. Ten patients not requiring IPM (noIPM) served as controls. Primary endpoint was hepatocellular injury during liver surgery reflected by systemic L-FABP plasma levels. Between group comparisons were performed using area under the curve and repeated measures two-way ANOVA. Results: The IPM groups had similar characteristics. Aminotransferases did not differ significantly between 15IPM and 30IPM at any time point. L-FABP levels rose up to 1853±708ng/ml in the 15IPM and 3662±1355ng/ml in the 30IPM group after finishing liver transection and decreased rapidly thereafter. There were no significant differences between 15IPM and 30IPM in cumulative L-FABP level (p =0.378) or L-FABP level at any time point (p =0.149). Blood loss, remnant liver function and morbidity were comparable. Conclusions: IPM with 15 or 30min ischemic intervals induced similar hepatocellular injury measured by the sensitive marker L-FABP. The present study confirms the results of earlier trials, suggesting that IPM with 30min ischemic intervals may be used. [Copyright &y& Elsevier]

Purpose: To determine the plasma level of liver-type fatty acid binding protein (L-FABP) in chronic hepatitis C (CHC), and to compare this to Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels. Methods: We tested 38 biopsy-proven CHC patients and 33 age- and sex- matched healthy controls in whom biopsy was not performed for ethical considerations. Patients with persistently elevated plasma aminotransferase levels (ALT and/or AST), and positive anti-HCV antibody and HCV-RNA results were included, but not those with liver cirrhosis, chronic alcohol consumption, severe and/or acute cardiac, renal, cerebrovascular or intestinal disease, seropositive for Hepatitis B virus or HIV. In addition to routine biochemical assessment, L-FABP was determined using a solid phase specific sandwich ELISA. Results: Plasma ALT and AST level were significantly higher in the patient group than in the control group (57.7±27.9 IU/L vs 19.0± 7.7 IU/L, p<0.01 and 44.5±19.2 IU/L vs 18.3± 4.2 IU/L, p<0.01, respectively). Plasma L-FABP was significantly higher in the patient group than in the control group (5480.3± 4387.8 ng/mL vs 1710.5± 911.6 ng/mL, p<0.01). No correlation was found between L-FABP and either of the enzyme levels. ROC analysis produced cut-off values above which the likelihood of CHC increased. The cut-off value was 27.5 IU/L for ALT and 23.5 IU/L for AST. The cut-off value for L-FABP was 2600 ng/mL. Conclusion: L-FABP is elevated significantly in CHC when compared to healthy controls, independent of aminotranferase levels. Further studies are warranted to evaluate the potential use of L-FABP in the setting of CHC. Conflict of interest: The authors have no conflict of interest to declare. [ABSTRACT FROM AUTHOR]

Context: Despite the myriad uses of Annona senegalensis Pers. (Annonaceae) leaves in folklore medicine of Nigeria, the basis is yet to be substantiated by scientific investigations. Objectives: To investigate the antioxidant ( in vitro and in vivo) and drug detoxification potential of aqueous extract of A. senegalensis leaves in CCl4-induced hepatocellular damage. Materials and methods: In vitro antioxidant activity of the aqueous extract of A. senegalensis leaves was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), H2O2, superoxide ion, 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS) and ferric ion models while in vivo antioxidant and drug detoxification activities of the extract at 100, 200, and 400 mg/kg body weight were done by assaying the levels of enzymic and non-enzymic indices in CCl4-induced hepatocellular damage. Results: The extract at 1 mg/mL scavenged DPPH, H2O2, superoxide ion, and ABTS radicals, whereas ferric ion was significantly (P <0.05) reduced. The levels of alkaline and acid phosphatases, alanine and aspartate aminotransferases, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, reduced glutathione, vitamins C and E, glutathione S-transferase, nicotinamide adenine dinucleotide (reduced):Quinone oxidoreductase, uridyl diphosphoglucuronyl transferase, malondialdehyde, and lipid hydroperoxide that decreased in CCl4 treated animals were significantly attenuated by the extract in a manner similar to the animals treated with the reference drug. Discussion and conclusion: The ability of the aqueous extract of A. senegalensis leaves to scavenge free radicals in vitro and reversal of CCl4-induced hepatocellular damage in rats suggest antioxidant and drug detoxification activities. Overall, this study has justified the rationale behind some of the medicinal uses of the plant in folklore medicine of Nigeria. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is an emerging metabolic-related disorder characterized by fatty infiltration of the liver in the absence of alcohol consumption. NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), which might progress to end-stage liver disease. This progression is related to the insulin resistance, which is strongly linked to the metabolic syndrome consisting of central obesity, diabetes mellitus, and hypertension. Earlier, the increased concentration of intracellular fatty acids within hepatocytes leads to steatosis. Subsequently, multifactorial complex interactions between nutritional factors, lifestyle, and genetic determinants promote necrosis, inflammation, fibrosis, and hepatocellular damage. Up to now, many studies have revealed the mechanism associated with insulin resistance, whereas the mechanisms related to the molecular components have been incompletely characterized. This review aims to assess the potential molecular mediators initiating and supporting the progression of NASH to establish precocious diagnosis and to plan more specific treatment for this disease. [ABSTRACT FROM AUTHOR]

Although studies have indicated that hemorrhagic shock and resuscitation produces hepatic damage by mechanisms involving adhesion molecules in endothelial cells and hepatocytes, it is not known if there is any difference in the extent of hepatic damage following bone fracture, soft tissue trauma, and hemorrhage (Fx-TH) between young and middle-aged animals. To study this, young (6-8 wk) and middle-aged (~12 mo) C3H/HeN male mice were subjected to a right lower leg fracture, soft tissue trauma, (i.e., midline laparotomy), and hemorrhage (blood withdrawal to decrease the blood pressure to 35 ± 5 mmHg for 90 mm) followed by resuscitation with four times the shed blood volume in the form of lactated Ringer solution. Mice were euthanized 24 h later, and liver tissues were harvested. Total bilirubin levels in the hepatocyte extract increased markedly following Fx-TH in both groups of mice; however, the increase in middle-aged mice was significantly higher compared with young mice. TNF-α and IL-6 levels in the hepatocyte extract following Fx-TH increased significantly in middle-aged mice but remained unchanged in young mice. IL- 10 levels significantly decreased in middle-aged mice following Fx-Th but remained unchanged in young mice. Kupifer cells from middle-aged mice produced significantly higher IL-6 and IL-10 levels compared with young mice. Protein levels and mRNA expression of ICAM-1 in hepatocytes were also significantly higher in middle-aged mice compared with young mice following Fx-TH. These results collectively suggest that the extent of hepatic damage following Fx-TH is dependent on the age of the subject. [ABSTRACT FROM AUTHOR]

To verify whether endotoxin (LPS) might act as a priming cofactor of liver injury caused by obstructing the duodenum, four groups of male Wistar rats were studied. The first two groups comprised rats in which a closed duodenal loop (CDL) was created: CDL, n = 6 and CDL + LPS, n = 7; the next two groups comprised sham-operated animals: Sham n = 6 and Sham + LPS, n = 6. LPS, 400 μg/kg bodyweight, was administered i.p. to the rats belonging to groups CDL + LPS and Sham + LPS, 24 h before laparotomy. Twenty-four hours after laparotomy the animals were killed. Damage to bile ducts, extent and grading of coagulative and lytic spotty necrosis in liver tissue were evaluated morphologically. Coagulative necrosis was severe in four of seven rats of the group CDL + LPS, mild in six of six rats of group CDL, and absent in four of six and five of six rats of groups Sham and Sham + LPS (χ2 32.8, P = 0.0001). The animals of group CDL + LPS had more frequently diffuse lytic spotty necrosis than the animals in the three other groups (χ2 9.57 P < 0.01). The results of our study indicate that, in rodents subjected to a closed duodenal loop, priming with LPS exacerbates liver injury due to cholate stasis. [ABSTRACT FROM AUTHOR]

Abstract: Heat stroke is the result of exposure to high environmental temperature and strenuous exercise representing a medical emergency characterized by an elevated core body temperature and central nervous system disorders. Slightly elevated liver enzymes, lacking clinical significance, seem to be frequent in heat stroke, whereas severe, clinically relevant, hepatocellular injury has been observed in only a minority of cases. In the present report we describe the case of an otherwise healthy young asylum-seeking refugee from East Timor, who developed severe heat stroke during his transportation to Greece in a closed container on a ship under unusually high temperatures. He was admitted to the hospital with severe multi-organ failure. After a short period of initial improvement, he developed severe hepatocellular injury and hepatic encephalopathy. Other causes of liver damage were excluded. The patient completely recovered. [Copyright &y& Elsevier]