Morphological Changes In Liver Research Articles

Effect of curcumin and cacao extract on interleukin-6 expression on ribociclib-induced hepatotoxicity in rats

Purpose: To assess the relationship between interleukin-6 (IL-6) expression and the protective effect of curcumin and cacao extract on hepatotoxicity caused by ribociclib. Method: Sixty adult male albino rats (9 – 10 weeks old) were utilized in this experiment. The rats were separated into six groups (n = 10 each). Group 1 (control) rats received 2 mL of normal saline daily. Group 2 rats were administered 5 mg/kg ribociclib and group 3 rats received 5 mg/kg ribociclib with a cacao dose of 200 mg/kg daily. Group 4 rats were administered 5 mg/kg ribociclib treated with curcumin (200 mg/kg) daily. Groups 5 and 6 were administered cacao and curcumin doses of 200 mg/kg daily. All rats were sacrificed and liver immunohistochemical and histological examinations were performed. Result: The findings demonstrated that ribociclib administration caused liver damage and morphological changes at a histological level in liver tissue. The immunohistochemical investigation revealed that IL-6 levels were significantly increased in group 2 and control group (p < 0.05). Furthermore, co-administration of curcumin and cacao with ribociclib suppressed the levels of IL-6 expression in the liver tissue of rats compared to control group 1. Conclusion: Co-administration of curcumin and cacao protects the liver against ribociclib-induced liver damage. It is necessary to determine the effect of long-term administration of these extracts on the functions of some organs such as the liver and kidney.

Cisplatin induces acute liver injury by triggering caspase-3/GSDME-mediated cell pyroptosis

BackgroundCisplatin triggers Gasdermin E (GSDME) cleavage, causing membrane bubble formation, content release, and inflammation. Caspase-3 activation initiates GSDME cleavage, and thus inhibiting this pathway mitigates cisplatin-induced pyroptosis in hepatocytes. This study aimed to delve into how cisplatin induces liver injury via pyroptosis. MethodsFor animal experiments, C57BL/6J mice were divided into three groups: control, liver injury model group, and Ac-DMLD-CMK (caspase-3 inhibitor) intervention group. The liver histology was evaluated by hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and TUNEL staining. The mRNA and protein levels were detected by real-time polymerase chain reaction (PCR) and Western blot analysis. For in vitro experiments, HL-7702 cells were treated with cisplatin or GSDME siRNA. Cell pyroptosis was determined via cellular morphology, cytotoxicity and viability detection, flow cytometric assay, and Western blot detection for the expression of pyroptosis-related proteins. ResultsCisplatin-induced distinct liver morphological changes, hepatocellular injury, and inflammation in mice, along with elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and increased pro-inflammatory cytokine expression. Heightened macrophage infiltration and hepatocellular death indicated cisplatin-induced hepatotoxicity. Cisplatin upregulated GSDME activation, along with Bax-mediated caspase-3 cleavage both in vivo and in vitro, implicating caspase-3/GSDME-dependent pyroptosis in liver injury. Treatment with Ac-DMLD-CMK ameliorated cisplatin-induced liver injury, reducing hepatocellular lesions, serum ALT and AST levels, cytokine expression, macrophage infiltration, and hepatocyte death. Ac-DMLD-CMK also attenuated GSDME-dependent pyroptosis post-cisplatin induction, as evidenced by decreased GSDME expression, Bax upregulation, and cleaved caspase-3 activation. For HL-7702 cells, GSDME siRNA transfection reduced GSDME expression, attenuated typical signs of cisplatin-induced pyroptosis, partially restored cell viability, and significantly inhibited cytotoxicity and a decrease in the proportion of propidium iodide-positive cells, indicating protection against cisplatin-induced hepatocyte pyroptosis. ConclusionOur study underscores the role of the caspase-3/GSDME signaling pathway in mediating cisplatin-induced hepatotoxicity, particularly in cases of excessive or cumulative cisplatin exposure. These findings suggest that targeting GSDME could represent a promising therapeutic approach to mitigate cisplatin-induced liver damage.

Imaging and Pathological Feature Analysis of Idiopathic Portal Hypertension

Background: Idiopathic portal hypertension (IPH) is a rare clinical condition often misdiagnosed as cirrhosis. The management of IPH focuses on preventing and treating complications related to portal hypertension, such as bleeding from esophagogastric fundal varices. In contrast, the management of cirrhosis focuses on symptomatic treatment based on etiology, protecting hepatocyte function, and inhibiting hepatic inflammation and fibrosis. Therefore, it is crucial to correctly recognize both diseases and take appropriate therapeutic measures. Objectives: The aim of this study was to summarize and analyze the imaging, pathological, and serological features of idiopathic portal hypertension and cirrhosis to reduce misdiagnosis in clinical practice. Patients and Methods: Pathological, radiological parameters [computed tomography (CT)/magnetic resonance imaging (MRI)], and serological examinations were retrospectively evaluated for 14 patients with IPH and 30 patients with cirrhosis. We analyzed and compared their imaging manifestations in terms of spleen thickness and length, liver morphology, hepatic lobe atrophy, hyperplasia, portal vein thrombosis, arteriovenous phase liver perfusion, regenerative nodules, focal nodular hyperplasia-like lesions of the liver, portal vein morphology, splenorenal shunt, and hepatorenal shunt. The aim was to investigate the correlation between the imaging manifestations and the pathological manifestations. Results: There were significant differences between the IPH and cirrhosis groups in individual indicators of liver function, routine blood tests, and coagulation function (P < 0.05). Significant differences in spleen thickness and length were also observed between the IPH and cirrhosis groups (P < 0.05). Atrophy and hyperplasia of the hepatic lobe differed between the two groups. Changes in liver morphology and parenchyma were observed in both the IPH and cirrhosis groups, with diffuse regenerative nodules and focal nodular hyperplasia-like lesions being significant for distinguishing between IPH and cirrhosis. Focal nodular hyperplasia-like lesions were more common in patients with idiopathic portal hypertension, whereas diffuse regenerative nodules were more common in patients with cirrhosis. All 14 IPH patients had abnormalities in the portal vein system, including main portal vein dilation, stiffness, straightening, and distal branch vein stenosis or occlusion, while 9 cirrhosis patients had portal vein abnormalities, primarily thinning of the portal vein. Pathology revealed that patients in the cirrhosis group had varying degrees of cell necrosis and edema, and pseudolobule formation was observed in all patients. Patients with IPH showed varying degrees of fibrosis in the portal and confluent areas, but lobular inflammation was not evident. Some IPH patients experienced portal vein occlusion and stenosis. Conclusion: Idiopathic portal hypertension is relatively rare in clinical practice and is characterized by mostly normal liver function and hypersplenism, which may lead to a decrease in platelets, red blood cells, and white blood cells. If a giant spleen is found on imaging and the liver surface is smooth, IPH should be considered. Additionally, fibrosis, stenosis, and occlusion of the portal venous system, as well as focal nodular hyperplasia-like lesions, are suggestive of idiopathic portal hypertension. In contrast, diffuse regenerative nodules and pseudolobule formation are often indicative of cirrhosis. Furthermore, atrophy and hyperplasia of the liver are significant in differentiating the two diseases.

Antitumor effect of Iso-mukaadial acetate on MCF-7 breast cancer mice xenograft model

Antitumor drugs used today have shown significant efficacy and are derived from natural products such as plants. Iso-mukaadial acetate (IMA) has previously been shown to possess anticancer properties by inducing apoptosis. The purpose of this study was to investigate the therapeutic effect of IMA in the breast cancer xenograft mice model. Female athymic nude mice were used and inoculated with breast cancer cells subcutaneously. Untreated group one served as a negative control and positive control group two (cisplatin) was administered intravenously. IMA was administered orally to group three (100 mg/kg) and group four (300 mg/kg). Blood was collected (70 μL) from the tail vein on day zero, day one and day three. Tumor regression was measured every second day and body mass was recorded each day. Estimation of serum parameters for renal indices was examined using a creatinine assay. Histopathological analysis was conducted to evaluate morphological changes of liver, kidney, and spleen tissues before and after compound administration under a fluorescence light microscope. Histopathological analysis of tumors was conducted before and after compound administration. Apoptotic analysis using the TUNEL system was conducted on liver, kidney, and spleen tissues. Tumor shrinkage and reduction in body mass were observed after treatment with IMA. Serum creatinine was slightly elevated after treatment with IMA at a dosage of 100 and 300 mg/kg. Histopathological results of the liver exhibited no changes before and after IMA while the kidney and spleen tissues showed changes in the cellular structure. IMA showed no cytotoxic effect on the tumor cells, and cell proliferation was observed. Apoptotic assay stain with TUNEL showed apoptotic cells in spleen tissue and kidney but no apoptotic cells were observed in liver tissue section treated with IMA. IMA showed clinical toxic signs that resulted in the suffering and death of the mice immediately after IMA administration. Histopathology of tumor cells showed that IMA did not inhibit cell proliferation and no cellular damage was observed. Therefore, based on the results obtained, we cannot make any definitive conclusion on the complete effect of IMA in vivo. IMA is toxic, poorly soluble, and not safe to use in animal studies. The objective of the study was not achieved, and the hypothesis was rejected.

Effects of electroacupuncture of different intensities and durations on PERK/ATF4/CHOP signaling pathway in liver of non-alcoholic fatty liver disease rats.

To analyze the effects of electroacupuncture (EA) at "Fenglong" (ST40) and "Zusanli" (ST36) of different intensities and durations on rats with non-alcoholic fatty liver disease (NAFLD) based on the protein kinase R-like endoplasmic reticulum kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP) signaling pathway, so as to explore its mechanism underlying improvement of NAFLD. SD rats were randomly divided into normal diet group, high-fat model group, sham EA group, strong stimulation EA (SEA) group, and weak stimulation EA (WEA) group, with 15 rats in each group. Each group was further divided into 2, 3, and 4-week subgroups. NAFLD rat model was established by feeding a high-fat diet. After successful modeling, rats in the SEA and WEA groups received EA at bilateral ST40 and ST36 with dense and sparse waves (4 Hz/20 Hz) at current intensities of 4 mA (SEA group) and 2 mA (WEA group), lasting for 20 minutes, once a day, 5 days a week with 2 days of rest. The sham EA group only had the EA apparatus connected without electricity. Different duration subgroups were intervened for 2, 3, and 4 weeks. After the intervention, the contents of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rats were detected by an automatic biochemical analyzer；liver morphological changes were observed by Oil Red O staining；real-time fluorescence quantitative PCR and Western blot were used to detect the expression of PERK, ATF4, and CHOP mRNAs and proteins in the rat liver tissue. In the high-fat model group, there was a significant accumulation of red lipid droplets in the liver cells, which was reduced significantly in the SEA group at the 4th week. Compared with the normal diet group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and proteins in the liver tissue were elevated (P<0.01) in the high-fat model group . Compared with the high-fat model group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, CHOP mRNAs and proteins in the liver tissue were decreased (P<0.01, P<0.05) in the SEA and WEA groups. Compared with the sham EA group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs were decreased (P<0.01, P<0.05) in the SEA and WEA groups, the expression of PERK, ATF4, and CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA group at the 2nd, 3rd, and 4th week, the expression of PERK and CHOP proteins at the 2nd, 3rd, 4th week and ATF4 protein at 2nd week in the liver tissue were decreased (P<0.01, P<0.05) in the WEA group. Compared with the SEA group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and proteins in the liver tissue were elevated (P<0.05, P<0.01) in the WEA group. Compared with the 2-week time point within the groups, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and PERK proteins in the liver tissue were decreased (P<0.01, P<0.05) in the SEA and WEA groups at 3rd and 4th week, the expression of ATF4 proteins in the liver tissue was decreased (P<0.01) in the SEA group at 3rd and 4th week, and the expression of CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA group at 4th week and in the WEA group at 3rd and 4th week. Compared with the 3-week time point within the groups, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs were significantly decreased (P<0.05, P<0.01) in the SEA and WEA groups at 4th week, the expression of PERK and CHOP proteins in the liver tissue was decreased (P<0.01) in the SEA and WEA groups at 4th week, and the expression of ATF4 protein in the liver tissue was decreased (P<0.05) in the SEA group at 4th week. EA at ST40 and ST36 can significantly improve liver function in NAFLD rats, and its mechanism of action may involve inhibiting PERK expression thereby targeting the downstream ATF4/CHOP signaling pathway to suppress endoplasmic reticulum stress, exerting a liver protective effect；the optimal effect was observed with EA intensity of 4 mA for 4 weeks.

Effect of Rutin on the Behavioural, Biochemical and Liver Morphological Changes in Danio Rerio Exposed to Reduced Graphene Oxide (Rgo) Nanoparticles

ABSTRACT: Reduced graphene oxide (rGO) is a carbon nanomaterial with unique characteristics that permit application in numerous fields. Rutin is a flavonoid with a variety of biological functions and pharmaceutical applications. In topical years, a handful of research has stated on the environmental impacts of carbon nanoparticles (NPs) and the consequences of reduced graphene oxide on the species that live in water bodies. However, the capacity to recuperate after exposure is still mostly unfamiliar. This study analyzed the protective effect of rutin against rGO NPs in zebrafish and the optimal dose required to inverse the impairment caused by rGO NPs exposure in zebrafish. In this study, fish were treated for 14 days and 8 study groups were examined: control, rGO exposure alone (10 mg/L), rutin exposure alone (50, 100 and 200 mg/L) and rGO combined with 3 distinct rutin doses (10 mg/L of rGO + rutin 50, 100, and 200 mg/L). In the zebrafish gill tissues, rGO impairs cells by increasing LPO levels and inducing oxidative stress by suppressing antioxidants (SOD, CAT, GPx, GSH, GR, GST, and vitamin C). Multiple alterations, including sinusoidal and venous congestion, vacuole formation or cytoplasmic vacuolation of hepatocytes, an enlarged hepatic plate gap, and necrosis, were revealed on the structural examination of liver tissues. Based on our results, we conclude that sub-lethal doses of rGO (10 mg/L) could be harmful to zebrafish. Rutin supplementation between 100 and 200 mg/L can protect against the toxic effects of rGO, even though rGO is detrimental to the exposed fish population.

Effects of carnosine combined with Lactobacillus on the antioxidant capacity of liver and kidney in normal or stressed mice

Massive secretion of glucocorticoids or excessive use of dexamethasone (Dex) can cause oxidative stress and negatively affect the health status of animals. The objective of this study was to investigate whether the use of Lactobacillus (LAB) or/and carnosine (CAR) can effectively improve the antioxidant capacity of the liver and kidneys of normal or dexamethasone-induced stress mice and its potential mechanisms. 48 ICR mice were randomly divided into eight groups: Control, LAB, CAR, LAB + CAR, Dex, Dex + LAB, Dex + CAR, and Dex + LAB + CAR. The results indicated that carnosine and Lactobacillus rhamnosus had a complementary effect on antioxidant stress. The combination of the two could better improve the increased serum ALT activity and CRE content, increased liver index, decreased kidney index, and changes in liver and kidney tissue morphology induced by dexamethasone in mice. Part of the involved mechanisms were: Carnosine combined with Lactobacillus rhamnosus promoted the expressions of downstream antioxidant genes SOD1, SOD2, GSH-Px1, and HO-1 by increasing Nrf2 expression in liver and kidney tissues. It also increased the contents of activated antioxidant enzymes SOD, GSH-Px, CAT, and HO-1, thereby reducing ROS and MDA levels and alleviating liver and kidney oxidative damage caused by dexamethasone.

Effects of dietary phytosterols or phytosterol esters supplementation on growth performance, biochemical blood indices and intestinal flora of C57BL/6 mice.

This study was conducted to evaluate the effects of phytosterols (PS) and phytosterol esters (PSE) on C57BL/6 mice. Three groups of 34 six-week-old C57BL/6 mice of specific pathogen free (SPF) grade, with an average initial body weight (IBW) of 17.7g, were fed for 24 days either natural-ingredient diets without supplements or diets supplemented with 89 mg/kg PS or diets supplemented with 400 mg/kg PSE. Growth performance, blood biochemistry, liver and colon morphology as well as intestinal flora status were evaluated. Both PS and PSE exhibited growth promotion and feed digestibility in mice. In blood biochemistry, the addition of both PS and PSE to the diet resulted in a significant decrease in Total Cholesterol (TC) and Triglyceride (TG) levels and an increase in Superoxide Dismutase (SOD) activity. No significant changes in liver and intestinal morphology were observed. Both increased the level of Akkermansia in the intestinal tract of mice. There was no significant difference between the effects of PS and PSE. It was concluded that dietary PS and PSE supplementation could improve growth performance, immune performance and gut microbiome structure in mice, providing insights into its application as a potential feed additive in animals production.

A bioactive compound digested chia protein is capable of modulating NFκB mediated hepatic inflammation in mice fed a high-fat diet

The consumption of diets high in saturated fat can induce damages in liver morphology and function, which leads to increased inflammation, oxidative stress, and hepatic steatosis. Chia seed (Salvia hispanica L.) is rich in protein, which provides bioactive peptides with potential benefits, including antioxidant and anti-inflammatory functions. Then, this study aimed to analyze the effect of digested total protein (DTP) of chia on inflammation, oxidative stress, and morphological changes in liver of C57BL/6 mice fed a diet rich in saturated fat. Male C57BL/6 mice (n = 8/group), 8 weeks old, were fed standard diet (AIN), high-fat diet (HF), standard diet added digested protein (AIN + DTP) or high-fat diet added digested protein (HF + DTP) for 8 weeks. In animals fed a high-fat diet, chia DTP was able to reduce weight gain, food efficiency ratio and hepatosomatic index. In addition, it presented antioxidant capacity, which reduced catalase activity and lipid peroxidation. DTP was also able to reduce hepatic inflammation by reducing p65-NFκB expression and IL-1β expression and quantification. The APSPPVLGPP peptide present in chia DTP presented binding capacity with PPAR-α, which contributed to the reduction of hepatic fat accumulation evidenced by histological analysis. Thus, chia DTP improved hepatic inflammatory and histological parameters, being an effective food in reducing the liver damage caused by a high-fat diet.

Pathophysiologic effects of waterpipe (shisha) smoke inhalation on liver morphology and function in mice

AimsThe global prevalence of waterpipe tobacco smoking is increasing. Although the cardiorespiratory, renal, and reproductive effects of waterpipe smoking (WPS) are well-documented, there is limited knowledge regarding its adverse impact on the liver. Therefore, our study aimed to assess the effects and potential mechanisms of WPS inhalation for one or four weeks on the liver. Main methodsMice were exposed to WPS for 30 min per day, five days per week, while control mice were exposed to clean air. Key findingsAnalysis using light microscopy revealed the infiltration of immune cells (neutrophils and lymphocytes) accompanied by vacuolar hepatic degeneration upon WPS inhalation. At the four-week timepoint, electron microscopy analysis demonstrated an increased number of mitochondria with a concomitant pinching-off of hepatocyte plasma membranes. WPS exposure led to a significant rise in the activities of liver enzymes alanine aminotransferase and aspartate aminotransferase in the bloodstream. Additionally, WPS inhalation elevated lipid peroxidation and reactive oxygen species levels and disrupted the levels of the antioxidant glutathione in liver tissue homogenates. The concentration of proinflammatory cytokines, including tumor necrosis factor α, interleukin (IL)-6, and IL-1β, was significantly increased in the WPS-exposed group. Furthermore, WPS inhalation induced DNA damage and a significant increase in the levels of cleaved caspase-3, cytochrome C and hypoxia-inducible factor 1α along with alterations in the activity of mitochondrial complexes I, II, III and IV. SignificanceOur findings provide evidence that WPS inhalation triggers changes in liver morphology, oxidative stress, inflammation, DNA damage, apoptosis, and alterations in mitochondrial activity.

Ticlopidine induces embryonic development toxicity and hepatotoxicity in zebrafish by upregulating the oxidative stress signaling pathway

Ticlopidine exerts its anti-platelet effects mainly by antagonizing platelet p2y12 receptors. Previously, a few studies have shown that ticlopidine can induce liver injury, but the exact mechanism of hepatotoxicity remains unclear. Oxidative stress, metabolic disorders, hepatocyte apoptosis, lipid peroxidation, and inflammatory responses can all lead to hepatic liver damage, which can cause hepatotoxicity. In this study, in order to deeply explore the potential molecular mechanisms of ticlopidine -induced hepatotoxicity, we used zebrafish as a model organism to comprehensively evaluate the hepatotoxicity of ticlopidine and its associated mechanism. Three days post-fertilization, zebrafish larvae were exposed to varying concentrations (1.5, 1.75 and 2 μg/mL) of ticlopidine for 72 h, in contrast, adult zebrafish were exposed exposure to 4 μg/mL of ticlopidine for 28 days. Ticlopidine-exposed zebrafish larvae showed changes in liver morphology, shortened body length, and delayed development of the swim bladder development. Liver tissues of ticlopidine-exposed zebrafish larvae and adults stained with Hematoxylin & Eosin revealed vacuolization and increased cellular interstitial spaces in liver tissues. Furthermore, using Oil Red O and periodic acid-Schiff staining methods and evaluating different metabolic enzymes of ticlopidine-exposed zebrafish larvae and adults suggested abnormal liver metabolism and liver injury in both ticlopidine-exposed zebrafish larvae and adults. Ticlopidine also significantly elevated inflammation and oxidative stress and reduced hepatocyte proliferation. During the rescue intervention using N-acetylcysteine, we observed significant improvement in ticlopidine-induced morphological changes in the liver, shortened body length, delayed swim bladder development, and proliferation of liver tissues showed significant improvement. In conclusion, ticlopidine might inhibit normal development and liver proliferation in zebrafish by upregulation of oxidative stress levels, thus leading to embryonic developmental toxicity and hepatotoxicity. In this study, we used zebrafish as a model organism to elucidate the developmental toxicity and hepatotoxicity induced by ticlopidine upregulation of oxidative stress signaling pathway in zebrafish, providing a theoretical basis for clinical application.

Chemotherapy-associated liver morphological changes in hepatic metastases (CALMCHeM).

To review imaging findings in chemotherapy-associated liver morphological changes in hepatic metastases (CALMCHeM) on computed tomography (CT)/magnetic resonance imaging (MRI) and its association with tumor burden. We performed a retrospective chart review to identify patients with hepatic metastases who received chemotherapy and subsequent follow-up imaging where CT or MRI showed morphological changes in the liver. The morphological changes searched for were nodularity, capsular retraction, hypodense fibrotic bands, lobulated outline, atrophy or hypertrophy of segments or lobes, widened fissures, and one or more features of portal hypertension (splenomegaly/venous collaterals/ascites). The inclusion criteria were as follows: a) no known chronic liver disease; b) availability of CT or MRI images before chemotherapy that showed no morphological signs of chronic liver disease; c) at least one follow-up CT or MRI image demonstrating CALMCHeM after chemotherapy. Two radiologists in consensus graded the initial hepatic metastases tumor burden according to number (≤10 and >10), lobe distribution (single or both lobes), and liver parenchyma volume affected (<50%, or ≥50%). Imaging features after treatment were graded according to a pre-defined qualitative assessment scale of "normal," "mild," "moderate," or "severe." Descriptive statistics were performed with binary groups based on the number, lobar distribution, type, and volume of the liver affected. Chi-square and t-tests were used for comparative statistics. The Cox proportional hazard model was used to determine the association between severe CALMCHeM changes and age, sex, tumor burden, and primary carcinoma type. A total of 219 patients met the inclusion criteria. The most common primaries were from breast (58.4%), colorectal (14.2%), and neuroendocrine (11.0%) carcinomas. Hepatic metastases were discrete in 54.8% of cases, confluent in 38.8%, and diffuse in 6.4%. The number of metastases was >10 in 64.4% of patients. The volume of liver involved was <50% in 79.8% and ≥50% in 20.2% of cases. The severity of CALMCHeM at the first imaging follow-up was associated with a larger number of metastases (P = 0.002) and volume of the liver affected (P = 0.015). The severity of CALMCHeM had progressed to moderate to severe changes in 85.9% of patients, and 72.5% of patients had one or more features of portal hypertension at the last follow-up. The most common features at the final follow-up were nodularity (95.0%), capsular retraction (93.4%), atrophy (66.2%), and ascites (65.7%). The Cox proportional hazard model showed metastases affected ≥50% of the liver (P = 0.033), and the female gender (P = 0.004) was independently associated with severe CALMCHeM. CALMCHeM can be observed with a wide variety of malignancies, is progressive in severity, and the severity correlates with the initial metastatic liver disease burden.

Retraction Note to: Effect of prenatal and perinatal acrylamide on the biochemical and morphological changes in liver of developing albino rat.

Retraction Note to: Effect of prenatal and perinatal acrylamide on the biochemical and morphological changes in liver of developing albino rat.

The health risk of acetochlor metabolite CMEPA is associated with lipid accumulation induced liver injury

Liver injury may cause many diseases, such as non-alcoholic fatty liver disease (NAFLD). Acetochlor is one of the representative chloroacetamide herbicides, and its metabolite 2-chloro-N-(2-ethyl-6-methyl phenyl) acetamide (CMEPA) is the main form of exposure in the environment. It has been shown that acetochlor can cause mitochondrial damage of HepG2 cells and induce apoptosis by activating Bcl/Bax pathway (Wang et al., 2021). But there has been less research on CMEPA. we explored the possibility of CMEPA and liver injury through biological experiments. In vivo, CMEPA (0–16 mg/L) induced liver damage in zebrafish larvae, including increased lipid droplets, changes in liver morphology (>1.3-fold) and increased TC/TG content (>2.5-fold). In vitro, we selected L02 (human normal liver cells) as the model, and explored its molecular mechanism. We found that CMEPA (0–160 mg/L) induced apoptosis (similar to 40%), mitochondrial damage and oxidative stress in L02 cells. CMEPA induced intracellular lipid accumulation by inhibiting AMPK/ACC/CPT-1A signaling pathway and activating SREBP-1c/FAS signaling pathway. Our study provides evidence of a link between CMEPA and liver injury. This raises concerns regarding the health risks of pesticide metabolites to liver health.

Liver cirrhosis following oxaliplatin-based adjuvant chemotherapy for rectal cancer.

Oxaliplatin is a third-generation platinum-based antineoplastic drug that is widely used to treat patients with colorectal cancer. Reported adverse reactions include hepatic sinusoidal obstruction syndrome and liver fibrosis, but there are few reports of cirrhosis associated with chemotherapy. In addition, the pathogenesis of cirrhosis remains unclear. We report a case of suspected oxaliplatin-induced liver cirrhosis, an adverse reaction that has not been previously reported. A 50-year-old Chinese man was diagnosed with rectal cancer and underwent laparoscopic radical rectal cancer surgery. The patient had a history of schistosomiasis, but history and serology showed no evidence of chronic liver disease. However, after five oxaliplatin-based chemotherapy cycles, the patient presented dramatic changes in liver morphology and developed splenomegaly, massive ascites, and elevated CA125 levels. Four months after discontinuing oxaliplatin, the patient's ascites had decreased significantly and CA125 levels declined from 505.3 to 124.6 mU/mL. After 15 weeks of follow-up, CA125 levels decreased to the normal range, and there has been no increase in ascites in this patient. Oxaliplatin-induced cirrhosis may be a serious complication and should be discontinued based on clinical evidence.

Morphological changes of liver and spleen under the impact of dextran-polyacrylamide polymers and their effects as carriers of silver and gold nanoparticles

The possibility of usage of polymer nanocomposites is being intensively studied today with a purpose of their application in medicine, espessialy in oncology. At the experimental stage it is important to determine the mechanisms of the influence of such compounds on the body and their own possible undesirable effects. Aim – to study the effect of the treatment with maximal doses of the dextran-polyacrylamide polymers and their effect as carriers of silver and gold nanoparticles on the spleen and liver. Histological examination of micropreparations of the spleen and liver by the standard method with hematoxylin-eosin staining was made. As a result of the treatment with nonionic (D-g-PAA) and anionic (D-g-PAA (PE)) polymer matrices, changes which occurred in the spleen indicate an increase in the production of all blood cells. These phenomena were absent when silver and gold nanoparticles were included in the matrix. In the liver, treatment with D-g-PAA and D-g-PAA (PE) caused a disorder of hepatic circulation, focal infiltration by inflammatory cells and death of hepatocytes by necrosis. The addition of nanoparticles triggered other mechanisms of alteration, which manifested themselves in excessive accumulation of glycogen, fatty infiltration of hepatocytes, and cell death, mainly through apoptosis. However, along with this, signs of an incomplete regenerative response of the liver were revealed. Morphological changes caused by the treatment with maximal doses of the tested substances indicate their toxic effect, especially on the liver. Further researches are needed to establish the optimal doses and the frequency of their administration, which can be used for therapeutic purposes, including the interaction of studied polymers with blood cells.

CD44-Targeting Drug Delivery System of Exosomes Loading Forsythiaside A Combats Liver Fibrosis via Regulating NLRP3-Mediated Pyroptosis.

Liver fibrosis is a progressive pathological process induced by various stimuli and may progress to liver cirrhosis and cancer. Forsythiaside A (FA) is an active ingredient extracted from traditional Chinese medicine Forsythiae Fructus and has prominent hepatoprotective activities. However, the unsatisfactory pharmacokinetic properties restrict its clinical application. In this study, the nanocarrier of CD44-specific ligand Hyaluronic acid (HA)-modified milk-derived exosomes (mExo) encapsulated with FA (HA-mExo-FA) is developed. As a result, HA modification could deliver drug-loaded exosomes to the target cells and form a specific ligand-receptor interaction with CD44, thus improving the anti-liver fibrosis effect of FA. In vitro findings indicate that HA-mExo-FA could inhibit TGF-β1-induced LX2 cell proliferation, reduce α-SMA and collagen gene and protein levels, and promote the apoptosis of activated LX2 cells. In vivo results demonstrate that HA-mExo-FA could improve liver morphology and function changes in zebrafish larvae. The anti-liver fibrosis mechanism of HA-mExo-FA may be attributed to the inhibition of NLRP3-mediated pyroptosis. In addition, the effect of HA-mExo-FA on TAA-induced increase in NLRP3 production is attenuated by NLRP3 inhibitor MCC950. Collectively, this study demonstrates the promising application of HA-mExo-FA in drug delivery with high specificity and provides a powerful and novel delivery platform for liver fibrosis therapy.

Sub-acute toxicity of graphene oxide (GO) nanoparticles in male mice after intraperitoneal injection: Behavioral study and histopathological evaluation.

Graphene oxide (GO) is a graphene derivative used for numerous applications in which biomedical uses are significant. However, for this application, the security of GO is doubtful. In this work, we synthesized this nanoparticle to assess its toxicity in male mice. In addition, we studied the effects of this nanomaterial on behavior by administering GO intraperitoneally to mice at different doses (2mg/kg and 5mg/kg) for five days. Subsequently, we performed biochemical analyses of blood serum and measured peroxidase and malondialdehyde (MDA) activity. Then, we performed histological sections to evaluate the brain's and liver's pathological and morphological changes. The data showed that the open field tests did not alter the locomotor activity. Furthermore, the elevated cross-maze tests showed no anxiety effect in the GO doses in the animals. The biochemical analyses indicated that GO influenced the level of biochemical parameters. Although, the oxidative stress assay showed an increase in peroxidase and MDA activity after GO intoxication. However, histopathological analysis of liver sections showed that GO caused liver inflammation, whereas, at the brain level, GO did not affect neuronal cells. The results indicate that GO caused toxic effects and that its toxicity could be mediated by oxidative stress.

Extracts from sojae semen germinatum ameliorated carbon tetrachloride-induced liver injury in mice

Sojae semen germinatum (SSG) prepared from the germinating black soybean Glycine max L. Merr. is a traditional Chinese herbal medicine with heat-clearing, dampness-removing, and detoxifying properties. In the present study, we explored the effects and possible underlying mechanisms of petroleum ether extract (PEE), ethyl acetate extract (EAE), n-butanol extract (NBE) and aqueous fraction (AF) of SSG on the carbon tetrachloride (CCl4)-induced liver injury in mice, an animal model representing pathological features of “dampness-heat” syndrome from the perspective of Traditional Chinese Medicine. Results showed that the EAE and NBE of SSG significantly protected mice against the CCl4-induced increases of liver tissue index and serum transaminase levels, ameliorated the CCl4-induced liver morphological changes. Compared with CCl4 model controls, EAE and NBE of SSG decreased malondiadehyde (MDA) levels, enhanced glutathione (GSH) content and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in liver tissues, as well as reduced the number of apoptotic hepatocytes. Moreover, the CCl4-induced increase of pro-inflammatory cytokine levels in livers was markedly suppressed by pre-treatment with EAE of SSG. Data suggested that SSG extracts showed protective effect on the CCl4-induced liver injury via multiple pharmacological mechanisms including anti-oxidation, anti-inflammation and anti-apoptosis. EAE and NBE appeared to be superior to other fractions.

Biochemical and Morphological Responses in Amazon Fish, Piaractus brachypomus Exposed To 2,4-D + Picloram Herbicide

Pesticides as herbicides present an elevated potential for contaminating the aquatic environment, being able to create negative effects for organisms that are not the target, like fish. We evaluated the morphology and function of the hepatic, branchial and renal tissue on Piaractus brachypomus exposed to the herbicide based on 2,4-D + Picloram. Fishes were exposed to a sublethal concentration of the herbicide Norton® (1.1 g L-1, corresponding to 420 mg L-1 of 2,4D and 100 mg L-1 of picloram) for 96 h. After exposure, the plasma, gills, liver, kidney and white muscle were sampled for biochemical and morphological analyses. Acute exposure induced an increase on plasmatic glucose and decrease of muscular glycogen, while the plasmatic protein was also decreased. Tissues GST-GSH enzymatic biotransformation pathway and lipid peroxidation (LPO) were unchanged after acute exposure. Histopathological indexes analysis showed alterations on gills, liver and kidney which was evidenced morphofunctional damage by histopathological organ indexes. The results demonstrate that the herbicide induce different organs responses characterized by morphological and metabolic alterations on P. brachypomus. The adjustments of energy demand and gill, liver and kidney morphological changes produced by Norton® may affect the capacity of vital functions and capacity for development and reproduction of the specie.