Increase In Liver Weight Research Articles

The effects of different VOCs on blood cells and biochemical parameters

Abstract. Volatile organic compounds (VOCs) poses serious hazards to the human body. Since 2010, the World Health Organization has been aware of the hazards of VOCs and has established quantitative standards for indoor air toxic substances that have an impact on physical health in the Indoor Air Quality Guidelines released that year. In animal model experiments, studies have shown that VOC leads to increased liver weight, liver damage, endocrine disorders, and blood related diseases. The relationship between human related blood and liver indicators and VOCs has thus received attention. Also due to the different types of VOCs, the mechanisms of their impact on the human body may vary, depending on the type of compound and the level of exposure to pollutants over time. This study comprehensively considered the possible effects of different types of VOCs on biochemical indicators and blood cells, then identified the various effects of different types of VOCs on biochemical indicators, aiming to explore the responding mechanisms of toxicity caused by different VOCs.

Noninvasive Monitoring of Steatotic Liver Disease in Western Diet-Fed Obese Mice Using Automated Ultrasound and Shear Wave Elastography.

Ultrasound imaging and shear wave elastography (SWE) can be used to noninvasively stage hepatopathologies and are widespread in clinical practice. These techniques have recently been adapted for small animal use in a novel 3D invivo imaging system capable of high-throughput automated scanning. Our goal was to evaluate the feasibility of using this imaging tool in the murine Western diet (WD) model, a highly translatable preclinical model of obesity, metabolic disease and liver fibrosis. Female C57BL/6 mice (N = 48) were placed on WD or chow diet and imaged longitudinally for a period of 48 weeks. Imaging consisted of 3D B-mode and targeted SWE captures. Liver volume, liver echogenicity and liver stiffness were quantified from invivo imaging data. A subset of mice was sacrificed at various timepoints (0, 12, 24 and 48 weeks) for histological workup. Correlation analysis was performed between invivo imaging and histological measurements to determine level of agreement. Noninvasive imaging showed statistically significant increases in liver volume and echogenicity, but non-significant increase in liver stiffness in the WD-fed cohort, suggesting development of hepatomegaly and steatosis, but negligible fibrosis. Exvivo analysis confirmed significant increases in liver weight, liver triglycerides and ALT, but limited increases in fibrosis corroborating noninvasive imaging results. Correlation analysis between imaging and histology demonstrated good agreement between liver volume/liver weight (R2 = 0.85) and echogenicity/triglycerides (R2 = 0.76). This study demonstrated that noninvasive ultrasound liver assessments are feasible in the WD mouse model and closely reflect the underlying pathological state of the animal. Automated ultrasound can serve as a high-throughput noninvasive screening method for preclinical liver disease research and drug development.

Rifaximin prophylaxis in MASLD‑hepatocellular carcinoma: Lessons from a negative animal model.

The incidence of hepatocellular carcinoma (HCC) has been rising, particularly among individuals diagnosed with metabolic dysfunction-associated steatotic liver disease. In the present study, the prophylactic effects of rifaximin (RIF) on HCC, inflammatory markers and cardiovascular risk (CVR) were investigated in an animal model. Adult Sprague-Dawley rats were randomly allocated into three groups (n=10, each): Control [standard diet/water plus gavage with vehicle (Veh)], HCC [high-fat choline deficient diet (HFCD)/diethylnitrosamine (DEN) in drinking water/Veh gavage] and RIF [HFCD/DEN/RIF (50 mg/kg/day) gavage] groups. After euthanasia at week 16, biochemical/inflammatory markers and the liver histology were assessed. The results demonstrated that the HCC and RIF animals had a significant increase in fresh liver weight, liver weight/body weight ratio, serum total cholesterol (TC), high-density lipoprotein-cholesterol, triglycerides, hepatic lipid accumulation and hepatic concentration of triglycerides and TC, relative to the controls (P<0.001, for all). Additionally, the HCC and RIF animals had higher plasminogen activator inhibitor, intercellular adhesion molecule-1, E-selectin and CVR scores than the controls (P<0.001, for all). The HCC animals had higher interleukin (IL)-1β (P=0.011), IL-10 (P<0.001), toll-like receptor-2 (P=0.012), lipopolysaccharide-binding protein (P=0.018) and metalloproteinase-2 (P=0.003) levels than the RIF animals. Furthermore, liver steatosis, inflammation and fibrosis, along with increased collagen fiber deposition occurred in the HCC and RIF groups. However, HCC occurred only in 2 RIF rats. In conclusion, although most animals did not develop HCC in the present study, RIF positively affected liver inflammation markers involved in steatohepatitis pathogenesis.

Deficiency of GPR10 and NPFFR2 receptors leads to sex-specific prediabetic syndrome and late-onset obesity in mice.

GPR10 and neuropeptide FF receptor 2 (NPFFR2) play important role in the regulation of food intake and energy homeostasis. Understanding the interaction between these receptors and their specific ligands, such as prolactin-releasing peptide, is essential for developing stable peptide analogs with potential for treating obesity. By breeding and characterizing double knockout (dKO) mice fed standard or high-fat diet (HFD), we provide insights into the metabolic regulation associated with the GPR10 and NPFFR2 deficiency. Both WT and dKO mice were subjected to behavioral tests and an oral glucose tolerance test. Moreover, dual-energy X-ray absorptiometry (DEXA) followed by indirect calorimetry were performed to characterize dKO mice. dKO mice of both sexes, when exposed to an HFD, showed reduced glucose tolerance, hyperinsulinemia, and insulin resistance compared with controls. Moreover, they displayed increased liver weight with worsened hepatic steatosis. Mice displayed significantly increased body weight, which was more pronounced in dKO males and caused by higher caloric intake on a standard diet, while dKO females displayed obesity characterized by increased white adipose tissue and enhanced hepatic lipid accumulation on an HFD. Moreover, dKO females exhibited anxiety-like behavior in the open field test. dKO mice on a standard diet had a lower respiratory quotient, with no significant changes in energy expenditure. These results provide insights into alterations associated with disrupted GPR10 and NPFFR2 signaling, contributing to the development of potential anti-obesity treatment.

Disruption of canonical AHR-mediated induction of hepatocyte PKM2 expression compromises antioxidant defenses and increases TCDD-induced hepatotoxicity

Metabolic reprogramming by the pyruvate kinase M2 isoform is associated with cell proliferation and reactive oxygen species (ROS) defenses. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant that induces ROS and hepatotoxicity, dose-dependently induces pyruvate kinase muscle isoform M2 (PKM2) in the liver. To further investigate its role in combating TCDD hepatotoxicity, a PkmΔDRE mouse was constructed lacking the dioxin response element mediating aryl hydrocarbon receptor (AHR) induction. TCDD failed to induce hepatic PKM2 in PkmΔDRE mice and in primary hepatocytes isolated from an AHR knockout model (AHRV375Afl/flAlb-CreERT2), demonstrating induction is AHR dependent. Both wild-type (WT) and PkmΔDRE mice exhibited dose-dependent increases in liver weight after treatment with TCDD every 4 days for 28 days. Glutathione (GSH) levels increased in WT mice while oxidized glutathione (GSSG) levels increased in both models with a 24-fold decrease in the GSH/GSSG ratio in PkmΔDRE mice suggesting lower antioxidant and recycling capacity. Moreover, TCDD-induced fibrosis was more severe in PkmΔDRE mice while PkmΔDRE hepatocytes exhibited greater cytotoxicity following co-treatment with TCDD and hydrogen peroxide. TCDD also induced PKM2 in human HepaRG™ cells with AHR enrichment at a conserved DRE core within the locus. These results suggest AHR-mediated PKM2 induction is a novel antioxidant response to TCDD.

MOR23 deficiency exacerbates hepatic steatosis in mice.

Hepatic steatosis, a common liver disorder, can progress to severe conditions such as nonalcoholic steatohepatitis and cirrhosis. While olfactory receptors are primarily known for detecting odorants, emerging evidence suggests that they also influence liver lipid metabolism. This study generated a mouse model with a specific knockout of olfactory receptor 23 (MOR23) to investigate its role in hepatic steatosis. MOR23 knockout mice on a normal diet showed a slight increase in liver weight compared to wild-type (WT) mice. When fed a high-fat diet (HFD), these knockout mice exhibited accelerated hepatic steatosis, indicated by increased liver weight and hepatic triglyceride levels. Our findings suggest that the cyclic adenosine monophosphate/protein kinase A/AMP-activated protein kinase pathway is involved in the role of MOR23, leading to the upregulation of peroxisome proliferator-activated receptor α, peroxisome proliferator-activated receptor-γ coactivator 1-α, and their target β-oxidation genes in the liver. MOR23 also appeared to regulate lipogenesis and free fatty acid uptake in HFD-fed mice, potentially by influencing sterol regulatory element-binding protein 1 activity. Notably, administering a potential MOR23 ligand, cedrene, attenuated hepatic steatosis in WT mice, but these effects were largely nullified in MOR23 knockout mice. These findings provide valuable insights into the invivo role of MOR23 in hepatic steatosis development.

High fat intake aggravates hyperlipidemia and suppresses fatty liver symptoms induced by a high-sucrose diet in rats.

Overconsumption of sucrose or fat is widely acknowledged as a prominent feature of unhealthy dietary patterns. Both factors commonly co-occur and are recognized as hallmarks of the Western diet, which is an important contributor to non-communicative diseases. In this study, we investigated the hazards of high sucrose or fat intake, either alone or in combination. Wistar rats were divided into four groups and fed a control starch diet, high-sucrose diet, high-fat diet, or high-sucrose/fat diet for 30 days. High fat intake increased body weight and visceral and subcutaneous adipose tissue weights. Both high-sucrose and -fat diets were associated with increased plasma triglyceride and glucose levels, and high sucrose also elevated plasma cholesterol levels. The combination of high sucrose and fat synergistically elevated plasma triglyceride levels. The high-sucrose diet increased liver weight and hepatic total lipid and triglyceride levels, whereas this increase was suppressed by the high-fat diet. The high sucrose increased the mRNA levels of hepatic genes involved in fatty acid synthesis and transport (ACLY, ACACA, FAS, ELOVL6, SCD1, SREBP1, and CD36), whereas the high fat suppressed the high sucrose-induced expression of these genes. We observed that high sucrose and fat contents differently exerted their effects on hyperlipidemia and fatty liver. Furthermore, high fat aggravated hyperlipidemia and suppressed fatty liver induced by high sucrose.

High-sucrose diet induces abnormalities in lipid metabolism through gut microbiome dysbiosis linked to five metronidazole-suppressed bacteria

Public attention to the correlation between excessive sucrose consumption and metabolic syndrome has facilitated research on its underlying mechanisms. Recent studies have newly identified the intestine, rather than the liver, as the predominant site of dietary fructose metabolism, which corrects the previous concepts and links the promotion of fatty liver and hyperlipidemia to gut microbiota dysbiosis, although the specific mode of action remains unclear. Here, we used microbiota suppression to identify the causative bacteria. Male Wistar rats were fed a starch or high-sucrose diet and orally administered two independent antibiotic treatments for four weeks. Metronidazole, neomycin, ampicillin, vancomycin, and their mixture were used to explore highly sucrose-responsive bacteria. Metronidazole and the mixture decreased or showed a tendency to decrease high-sucrose diet-induced increases in liver weight, plasma triglyceride levels, and fatty acid synthesis-related gene expression (ATP citrate lyase, fatty acid synthase, and malic enzyme). To further investigate the ability of metronidazole to ameliorate high-sucrose diet-induced abnormalities in lipid metabolism, three nitroimidazole antibiotics (metronidazole, tinidazole, and ornidazole) were used. Only metronidazole reduced the liver weight and decreased plasma triglyceride levels on a high-sucrose diet. Among the high-sucrose diet induction effects, five bacteria suppressed by metronidazole were screened, belonging to the family Rikenellaceae, genera Bacteroides, Blautia, and Dorea, and species Eubacterium dolichum. Overall, suppression of the gut microbiota by metronidazole-specific action, rather than the nitroreductase activity of tinidazole and ornidazole, was responsible for the amelioration of high-sucrose diet-induced fatty liver and hypertriglyceridemia. Five causative bacteria were identified in this study.

Thymol, a Dietary Monoterpene, Abrogates Hexachlorobenzene-Induced Hepatic Dysfunction Via Different Mechanisms

Thymol (2-isopropyl-5-methyl-phenol) is a natural monoterpene phenolic antioxidant that has anti-inflammatory and anti-apoptotic potentials in experimental studies. Literatures are scarce on effects of hexachlorobenzene-induced hepatic damage. Therefore, this study investigated the ameliorating potential of thymol (THY) on hexachlorobenzene (HCB)-induced hepatic damage as well as the effects on the antioxidant status, polyamine catabolism, inflammatory and apoptotic processes. Thirty-two adult male rats were daily treated orally by gavage for 25 days and allocated into four groups; control group received corn oil, HCB alone group (15 mg/kg b.wt), THY-treated group (100 mg/kg b.wt) and HCB + THY-treated group. The results showed that HCB significantly reduced the body weight with concurrent increase in relative liver weight accompanied by widespread histological aberrations. Furthermore, HCB-treated rats revealed increases in hepatic putrescine oxidase, spermine oxidase, and myeloperoxidase activities, tumor necrosis-α and interleukin-1β levels, caspase-3 activity, induced oxidative damage as evidenced by elevated malondialdehyde (MDA) levels and significant reduction in antioxidant enzyme activities and reduced glutathione (GSH). However, co-administration of THY with HBC abated the hepatic damage by preventing the generation and release of reactive oxygen species, improving the antioxidant system, down-regulated polyamine catabolism, inflammatory and apoptotic responses. The findings of this study revealed that HCB acts as a hepatotoxicant and thymol might be a possible future therapeutic agent for HCB-induced hepatic damage.

Polysaccharide of Atractylodes macrocephala Koidz alleviates NAFLD-induced hepatic inflammation in mice by modulating the TLR4/MyD88/NF-κB pathway

Non-alcoholic fatty liver disease (NAFLD) not only could cause abnormal lipid metabolism in the liver, but also could cause liver inflammation. Previous studies have shown that Polysaccharide of Atractylodes macrocephala Koidz (PAMK) could alleviate animal liver inflammatory damage and alleviate NAFLD in mice caused by high-fat diet(HFD), but regulation of liver inflammation caused by NAFLD has rarely been reported. In this study, an animal model of non-alcoholic fatty liver inflammation in the liver of mice was established to explore the protective effect of PAMK on the liver of mice. The results showed that PAMK could alleviate the abnormal increase of body weight and liver weight of mice caused by HFD, alleviate the abnormal liver structure of mice, reduce the level of oxidative stress and cytokine secretion in the liver of mice, and downregulate the mRNA expression of TLR4, MyD88, NF-κB and protein expression of P-IκB, P-NF-κB-P65, TLR4, MyD88, NF-κB in the liver. These results indicate that PAMK could alleviate hepatocyte fatty degeneration and damage, oxidative stress and inflammatory response of the liver caused by NAFLD in mice.

High fat diet-induced obesity and gestational DMBA exposure alter folliculogenesis and the proteome of the maternal ovary†.

Obesity and ovotoxicant exposures impair female reproductive health with greater ovotoxicity reported in obese relative to lean females. The mother and developing fetus are vulnerable to both during gestation. 7,12-dimethylbenz[a]anthracene (DMBA) is released during carbon combustion including from cigarettes, coal, fossil fuels, and forest fires. This study investigated the hypothesis that diet-induced obesity would increase sensitivity of the ovaries to DMBA-induced ovotoxicity and determined impacts of both obesity and DMBA exposure during gestation on the maternal ovary. Female C57BL/6J mice were fed a control or a High Sugar High Fat (45% kcal from fat; 20% kcal from sucrose) diet until ~30% weight gain was attained before mating with unexposed males. From gestation Day 7, mice were exposed intraperitoneally to either vehicle control (corn oil) or DMBA (1mg/kg diluted in corn oil) for 7 d. Thus, there were four groups: lean control (LC); lean DMBA exposed; obese control; obese DMBA exposed. Gestational obesity and DMBA exposure decreased (P < 0.05) ovarian and increased liver weights relative to LC dams, but there was no treatment impact (P > 0.05) on spleen weight or progesterone. Also, obesity exacerbated the DMBA reduction (P < 0.05) in the number of primordial, secondary follicles, and corpora lutea. In lean mice, DMBA exposure altered abundance of 21 proteins; in obese dams, DMBA exposure affected 134 proteins while obesity alone altered 81 proteins in the maternal ovary. Thus, the maternal ovary is impacted by DMBA exposure and metabolic status influences the outcome.

Hepatocyte-specific loss of melanocortin 1 receptor disturbs fatty acid metabolism and promotes adipocyte hypertrophy.

Melanocortins mediate their biological functions via five different melanocortin receptors (MC1R - MC5R). MC1R is expressed in the skin and leukocytes, where it regulates skin pigmentation and inflammatory responses. MC1R is also present in the liver and white adipose tissue, but its functional role in these tissues is unclear. This study aimed at determining the regulatory role of MC1R in fatty acid metabolism. Male recessive yellow (Mc1re/e) mice, a model of global MC1R deficiency, and male hepatocyte-specific MC1R deficient mice (Mc1r LKO) were fed a chow or Western diet for 12 weeks. The mouse models were characterized for body weight and composition, liver adiposity, adipose tissue mass and morphology, glucose metabolism and lipid metabolism. Furthermore, qPCR and RNA sequencing analyses were used to investigate gene expression profiles in the liver and adipose tissue. HepG2 cells and primary mouse hepatocytes were used to study the effects of pharmacological MC1R activation. Chow- and Western diet-fed Mc1re/e showed increased liver weight, white adipose tissue mass and plasma triglyceride (TG) concentration compared to wild type mice. This phenotype occurred without significant changes in food intake, body weight, physical activity or glucose metabolism. Mc1r LKO mice displayed a similar phenotype characterized by larger fat depots, increased adipocyte hypertrophy and enhanced accumulation of TG in the liver and plasma. In terms of gene expression, markers of de novo lipogenesis, inflammation and apoptosis were upregulated in the liver of Mc1r LKO mice, while enzymes regulating lipolysis were downregulated in white adipose tissue of these mice. In cultured hepatocytes, selective activation of MC1R reduced ChREBP expression, which is a central transcription factor for lipogenesis. Hepatocyte-specific loss of MC1R disturbs fatty acid metabolism in the liver and leads to an obesity phenotype characterized by enhanced adipocyte hypertrophy and TG accumulation in the liver and circulation.

Treatment with 1.25% cholesterol enriched diet produces severe fatty liver disease characterized by advanced fibrosis and inflammation and impaired autophagy in mice

Nonalcoholic fatty liver disease (NAFLD) is reaching pandemic proportions due to overnutrition. The understanding of advanced stages that recapitulate the human pathology is of great importance to get a better mechanistic insight. We hypothesized that feeding of WT (C57BL) mice with a diet containing a high content of fat (21%), sugar (41.5%) and 1.25% of cholesterol (called from now on high fat, sucrose and cholesterol diet, HFSCD) will reproduce the characteristics of disease severity. Analysis of 16 weeks HFSCD-fed mice demonstrated increased liver weight and plasmatic liver damage markers compared with control diet (CD)-fed mice. HFSCD-fed mice developed greater hepatic triglyceride, cholesterol and NEFA content, inflammation and NAFLD activity score (NAS) indicating an advanced disease. HFSCD-fed mice displayed augmented hepatic total CD3+ T and Th9 lymphocytes, as well as reduced Th2 lymphocytes and CD206 anti-inflammatory macrophages. Moreover, T cells and anti-inflammatory macrophages correlated positively and inversely, respectively, with intrahepatic cholesterol content. Consistently, circulating cytotoxic CD8+ T lymphocytes, Th1, and B cell levels were elevated in HFSCD-fed WT mice. Hepatic and adipose tissue expression analysis demonstrated changes in fibrotic and metabolic genes related with cholesterol, triglycerides, and fatty acid synthesis in HFSCD-fed WT. These mice also exhibited reduced antioxidant capacity and autophagy and elevated ERK signaling pathway activation and CHOP levels. Our results indicate that the feeding with a cholesterol-enriched diet in WT mice produces an advanced NAFLD stage with fibrosis, characterized by deficient autophagy and ER stress along with inflammasome activation partially via ERK pathway activation.

Role of HNF4alpha-cMyc interaction in liver regeneration after partial hepatectomy.

Hepatocyte nuclear factor 4 alpha (HNF4α) is the master regulator of hepatic differentiation. Recent studies have also revealed the role of HNF4α in hepatocyte proliferation via negatively regulating the expression of proto-mitogenic genes, including cMyc. Here, we aimed to study the interaction between HNF4α-cMyc during liver regeneration after partial hepatectomy (PHX). Wild-type (WT), hepatocyte-specific knockout of HNF4α (HNF4α-KO), cMyc (cMyc-KO), and HNF4α-cMyc double knockout (DKO) mice were subjected to PHX to induce liver regeneration. Blood and liver tissue samples were collected at 0h, 24h, 48h, 7D, and 14D after PHX for further analysis. WT, HNF4α-KO, cMyc-KO and DKO mice regained liver weight by 14 days after PHX. The deletion of cMyc did not affect liver regeneration, which was similar to the WT mice. WT and cMyc-KO mice started regaining liver weight as early as 24 hours after PHX, with a peak proliferation response at 48 hours after PHX. HNF4α- KO and DKO showed a delayed response with liver weight increase by day 7 after PHX. The overall hepatocyte proliferation response by DKO mice following PHX was lower than that of other genotypes. Interestingly, the surviving HNF4α-KO and DKO mice showed re-expression of HNF4α at mRNA and protein levels on day 14 after PHX. This was accompanied by a significant increase in the expression of Krt19 and Epcam, hepatic progenitor cell markers, in the DKO mice on day 14 after PHX. These data indicate that, in the absence of HNF4α, cMyc contributes to hepatocyte-driven proliferation to compensate for the lost tissue mass. Furthermore, in the absence of both HNF4α and cMyc, HPC-driven proliferation occurs to support liver regeneration.

Influence of Varied Dietary Cholesterol Levels on Lipid Metabolism in Hamsters.

Syrian hamsters are valuable models for studying lipid metabolism due to their sensitivity to dietary cholesterol, yet the precise impact of varying cholesterol levels has not been comprehensively assessed. This study examined the impact of varying dietary cholesterol levels on lipid metabolism in Syrian hamsters. Diets ranging from 0% to 1% cholesterol were administered to assess lipid profiles and oxidative stress markers. Key findings indicate specific cholesterol thresholds for inducing distinct lipid profiles: below 0.13% for normal lipids, 0.97% for elevated LDL-C, 0.43% for increased VLDL-C, and above 0.85% for heightened hepatic lipid accumulation. A cholesterol supplementation of 0.43% induced hypercholesterolemia without adverse liver effects or abnormal lipoprotein expression. Furthermore, cholesterol supplementation significantly increased liver weight, plasma total cholesterol, LDL-C, and VLDL-C levels while reducing the HDL-C/LDL-C ratio. Fecal cholesterol excretion increased, with stable bile acid levels. High cholesterol diets correlated with elevated plasma ALT activities, reduced hepatic lipid peroxidation, and altered leptin and CETP levels. These findings underscore Syrian hamsters as robust models for hyperlipidemia research, offering insights into experimental methodologies. The identified cholesterol thresholds facilitate precise lipid profile manipulation, enhancing the hamster's utility in lipid metabolism studies and potentially informing clinical approaches to managing lipid disorders.

Tranilast Inhibits TRPV2 and Suppresses Fibrosis Progression and Weight Gain in a NASH Model Mouse.

This study aimed to investigate the role of transient receptor potential vanilloid 2 (TRPV2) in a mouse model with non-alcoholic steatohepatitis (NASH) and to examine the effects of tranilast on TRPV2 and fibrosis-related cytokines. C57BL/6N mice were fed a Gubra-Amylin NASH (GAN) diet for 20 weeks to induce NASH. The tranilast groups received oral administration of tranilast at doses of 300, 400 and 500 mg/kg/day, five days per week for 20 weeks, in addition to the GAN diet. The effects of tranilast were assessed based on the dosage of food intake, changes in body weight, liver weight, blood biochemical parameters, histopathological examination, and expression of TRPV2 and inflammatory cytokines. Hepatic expression of TRPV2 was observed in the GAN-fed NASH mouse model. The tranilast groups showed significantly suppressed increases in body and liver weights. The development of intrahepatic fat deposition and liver fibrosis, assessed histopathologically, was inhibited. Tranilast administration improved the expression of TRPV2 and inflammatory cytokines in the liver. Additionally, blood tests indicated a reduction in elevated liver enzyme levels. In GAN diet NASH models, TRPV2 was up-regulated in the liver and tranilast inhibited TRPV2 and suppressed fibrosis. Therefore, it might prevent the incidence of hepatocellular carcinoma associated with NASH.

General toxicity and screening of reproductive and developmental toxicity following bioaccumulation of oral-dosed perfluorooctanoic acid: Loss of the Golgi apparatus

Despite its widespread use as a stabilizer across various industries over the past several decades, the health effects of chronic exposure to PFOA are still unclear. We administered PFOA by oral gavage (0, 12.5, 50, and 200 μg/day/mouse, eight groups) to male and female mice for six months. Body weight gain decreased with dose accompanied by increased liver weight, and PFOA altered liver damage-related-blood biochemical indicators and induced pathological lesions, including hepatocellular hypertrophy, cholangiofibrosis, and centrilobular hepatocellular vacuolation. Loss of the Golgi apparatus, formation of lamellar body-like structures, and lipid accumulation were observed in the liver of PFOA-treated mice. We also cohabited five pairs of male and female mice for the last ten days of administration, dosed PFOA to dam up to 28 days after birth, and investigated effects on reproduction and development. The survival rate of pups and the sex ratio of surviving mice decreased significantly at the highest dose. PFOA tissue concentration increased with the dose in the parent mice's liver and the pups' blood and brain. Taken together, we suggest that PFOA primarily affects the liver and reproduction system and that disturbance in lipid metabolism and Golgi's structural stability may be involved in PFOA-induced toxicity.

Metabolic Profiling Changes Induced by Fermented Blackberries in High-Fat-Diet-Fed Mice Utilizing Gas Chromatography-Mass Spectrometry Analysis.

The aim of this study was to investigate the metabolic changes associated with the anti-obesity effects of fermented blackberry extracts in the liver tissues of high-fat-diet-fed mice using mass spectrometry-based metabolomics analysis. C57BL/6J mice were divided into eight groups: normal-diet-fed mice, high-fat-diet-fed mice, high-fat diet treated with blackberry extract, high-fat-diet mice treated with blackberry fermented by L. plantarum, and high-fat diet with blackberry fermented by L. brevis. After 12 weeks, the high-fat-diet group exhibited a greater increase in liver weight compared to the control group, and among the groups, the group administered with blackberry fermented with L. plantarum showed the most pronounced reduction in liver weight. As the primary organ responsible for amino acid metabolism, the liver is crucial for maintaining amino acid homeostasis. In our study, we observed that the levels of several essential amino acids, including isoleucine and valine, were decreased by the high-fat diet, and were recovered by administration of blackberry extract fermented with L. plantarum. Our results demonstrated the potential of blackberry extract fermented with L. plantarum as a functional material for metabolic disorders by restoring some of the amino acid metabolism disturbances induced by a high-fat diet.

Hepatic transcriptomic assessment of Sprague Dawley rats in response to dietary perfluorobutane sulfonate (PFBS) ingestion

Perfluorobutane sulfonate is a short-chain PFAS that is a less toxic replacement for the rather more toxic long-chain perfluorooctane sulfonate. PFBS is widespread in the environment and has raised environmental and health concerns. The study goal was to investigate whether dietary ingestion of PFBS would induce hepatic damage. Sprague-Dawley rats were assigned to three PFBS treatment groups for 11 weeks followed by clinical markers analyses in the serum and liver. There was a significant increase in liver and body weights of PFBS rats. Total antioxidant capacity was significantly reduced in the PFBS-treated group. ALT levels increased based on concentration ingested. Close to 1000 gene transcripts were differentially expressed. Further, transmembrane transport and oxidation-reduction processes were the most up-regulated biological processes. Inflammatory genes were up-regulated in the exposed group and those associated with oxidative damage were down-regulated. In conclusion, PFBS ingestion produced mild effects in the liver of Sprague Dawley rats.

The Protective Role of Nigela Sativa Volatile Oil on Antioxidant and Oxidative Stress Enzymes

Hepatotoxicity is the outcome of a paracetamol overdose.In this study, 40 adult male rats, weighing 180–260 gm and aged between 9 and 13 weeks, were given doses of Nigela sativa oil and their liver enzymes were examined to see how paracetamol affected them. The rats were kept in an environment at a temperature of 25 Co in an animal house. ,There were four groups of rats, and food was provided for them. (G). (G1) The only injections given to the control group are food and regular saline (0.9% of the time). (G2) 200 mg/kg of N. sativa and (G3) 400 mg/kg of paracetamol Addition of 400 mg/kg body weight of paracetamol. supplying 300 mg/kg B.W. of N. sativa to (G4)400 milligrams/kg B.W. of aspirin. Rat G2, GPT 87.80 IUL, and GOT hepatic enzyme concentration (129.32 IUL) all exhibit significant increases in comparison to the control. Furthermore, the levels of the liver GSH enzyme in rats (G2 )1.24 IUL shown a substantial increase, whereas G3 ( GOT ) 91.9 IUL, (GPT )76.70 IUL, and group (G4) GOT 109.88 IUL and enzyme (GPT ) 55.66 IUL exhibited significant declines as compared with control. While MDA enzyme in rats G2 (0.259 IUL) shows a major increase in comparison to the control, rats G3 (0.139 IUL) and G4 (0.112) show a noticeable decrease in comparison to G2. While body weight indicates that G2's outcomes are significantly lower than those of the other three groups. Groups G3 (2.55 gm) and G4 (2.7 gm) demonstrated a significant rise in liver weight compared to controls and G2, whereas groups G2 (24.23 gm) demonstrated a significant increase in liver weight compared to controls and group G2. Male rats in groups G2 (1.7 gm) demonstrated a significant drop in liver weight compared to controls.