Histopathological Changes In Liver Research Articles

Acute Oral Toxicity Assessment of Repchol in Wistar Rats: A Liver-protective Herbal Premix for Poultry

The present study was conducted for the assessment of acute oral toxicity and safety analysis of Repchol Premix (M/s Ayurvet Limited) according to OECD-423 guidelines. Six adult Wistar rats, weighing 113-134 g, were used for the study. After oral administration of Repchol@ 300 and 2000mg/kg body weight, the animals were observed for manifestation of toxic effect and death upto14 days. Evaluation of safety analysis and toxicity was assessed on the basis of presence of mortality or toxicity symptoms. Every animal in group served as its own control. At the end of experiment blood biochemical parameters and histopathological changes in heart, liver, kidney and lung were studied. The results showed that Repchol did not produce toxic effects or mortality during the experimental period. The body weight changes observed for two weeks were in the normal range. In Repchol treated rats biochemical parameters like AST, ALT, ALP and creatinine were observed within normal range and in histopathological examination no significant microscopic alterations were observed. Thus, the observations indicated that Repchol Premix did not produce toxic effect or acute oral toxicity and the LD50 of compound is beyond 2000mg/kg.

Impact of dietary exposure to polyester microfibers on hematology, serology and histology in a mouse model

Synthetic fabrics, especially polyester, are a primary source of microplastic fibers (MFs), but there is limited data on their accumulation and dose related health impact in living organisms. This study examined the effects of ingested polyester microfibers (PE-MFs) on hematology, histopathology, and serum biochemistry in albino mice. Mice were given varying doses of PE-MFs (100, 200, 400 and 800 μg/d/mice) for a duration of thirty-five days and a notable decreases in certain hematological parameters such as RBCs, Hb, and platelets, and increases in MCV and MCH was noted at (p < 0.05) thereby indicating possible inflammatory response within the body resulting from ingestion of these MFs. Liver enzymes (ALT, AST, and alkaline phosphatase) and histopathological changes in the liver and gastrointestinal tract also exhibited significant variations, with higher levels seen in the group receiving the highest dose of PE-MFs (800 μg/d/mice). In summary, increased exposure to PE-MFs led to a dose-related impact and notable alterations in histopathological, hematological, and serum biomarkers in albino mice. This study highlights the potential hazards associated with dietary exposure to PE-MFs in mammals and emphasizes the need for further research in this field.

Corilagin inhibits human cytomegalovirus infection and replication via activating the cGAS-STING signaling pathway in vitro and in vivo

AimThe existence of human cytomegalovirus (HCMV) is extremely widespread, causing serious diseases in patients with low immune function. The purpose of this study is to explore the efficacy and mechanism of Corilagin in the control of CMV infection, in order to provide scientific basis for the control of CMV infection. MethodsOur study employed an animal model in Balb/c mice, infected with MCMV, alongside cellular models in HFF cells and THP-1 cells, stimulated with HCMV. The expression of cGAS-STING signaling pathway molecules was detected in liver tissue, lung tissue, serum, cells and cell supernatant. The liver function and histopathological changes of mice were evaluated. ResultsIn vivo and in vitro experiments showed that Corilagin significantly inhibits CMV levels and attenuates pathological damage in liver and lung tissues in vivo, and similarly inhibits viral load in cells in vitro. Corilagin promotes the expression levels of STING and its downstream molecules in vivo and in vitro. Inhibition/down-regulation of STING significantly promotes CMV replication, on the contrary, activation/up-regulation of STING inhibits CMV replication, and Corilagin also promotes the expression levels of molecules related to the cGAS-STING signaling pathway in the above cases. ConclusionCorilagin could effectively inhibit the infection and replication of CMV in vitro and in vivo, which may be through the activation of cGAS-STING signaling pathway.

Active Role of Lactoferrin on Arsenic and Imidacloprid Toxicity in Broiler Chicks

Abstract This work aimed to evaluate the lactoferrin (LF) effect on arsenic (As) and imidacloprid (IMI) toxicity in broiler chicks. One-week old broiler chicks (n=105) were divided into seven groups (x15 each). The animals were orally supplemented with As, IMI, and/or LF for 4 weeks as follows: Control (G1) no supplements, G2 supplemented with As, G3 supplemented with IMI, G4 supplemented with As+IMI, G5 supplemented with As+LF, G6 supplemented with IMI+LF, G7 supplemented with As+IMI+LF. Body weight and weight gain were recorded on weekly interval. Blood, serum, liver, kidney, and muscle samples were collected at the end of the experimental period for biochemical and histopathological examination. Body weight performance, hematological, serum, and liver tissue biochemical analysis revealed adverse changes in G2, G3, and G4 compared to control, G5, G6, and G7. There was higher tissue residue of As and IMI in G4 and G5 compared to G5, G6, and G7. Liver histopathological changes in the groups supplemented with As and/or IMI were observed with necrosis, congestion, and inflammatory cell aggregates. The use of LF in broiler chicks improves weight gain performance and modulates the adverse effects of As and/or IMI toxicity.

A Prospective Study Of Histo-Pathological Changes In Lungs, Liver And Kidneys In Burns Cases Autopsied At A Tertiary Care Hospital

Introduction: Medico legal deaths including burns claim a substantial number of lives in central Karnataka.‘A Prospective Study of Histo-Pathological changes in Lungs, Liver and Kidneys in Burns Cases’ was carried out at the Department of Forensic Medicine &amp; Toxicology, SS hospital, SSIMS &amp; RC, Davangere. Material &amp; methods: The present study was carried out for the period of 3 years from January 2021 to December2023. Totally 100 cases with burns and scalds injuries brought to the mortuary for autopsy was the material for study and collection of tissues for histopathological examination. Observations &amp; Results: In the present study, histopathological changes in lungs showed congestion, pulmonary edema, Diffuse alveolar damage or ARDS changes, bronchopneumonia, interstitial pneumonitis, anthracotic pigment, carbon laden macrophages, intravascular thrombi, septic emboli, interstitial &amp; intra alveolar hemorrhage. Histopathological changes in liver showed congestion, fatty change, centrilobular necrosis, cloudy swelling, focal hemorrhage, necrosis, portal inflammation. Histopathological changes in kidneys showed ATN in majority of cases, cloudy degeneration, congestion, tubular casts and acute pyelonephritis in rest of the cases. Conclusion: The effect of burns on vital organs can be assessed through histopathological examination, which helps in determining the post burn complications and which aid in better treatment outcome of the burn’s patients.

Establishment of enterically transmitted hepatitis virus animal models using lipid nanoparticle-based full-length viral genome RNA delivery system

BackgroundEnterically transmitted hepatitis viruses, such as hepatitis A virus (HAV) and hepatitis E virus (HEV), remain notable threats to public health. However, stable and reliable animal models of HAV and...

Protective Effect of Banana, Cassava, and Corn Flours on Hepatotoxicity of Malnourished Male Rats

Background: Malnutrition-induced hepatotoxicity is defined as liver damage caused by insufficient nutrition, which results in oxidative stress and damage to liver cells. Objectives: The present study aimed to investigate the protective effects of banana, cassava, and corn flours on hepatotoxicity induced by malnutrition in male rats. Methods: Twenty-four male rats were divided into six groups (n=4): (1) rats received 30 g/rat normal feed daily for 45 days; (2) rats received 30 g malnutrition feed daily for 45 days; rats received 30 g/rat malnutrition feed daily for 15 days and then treated with normal feed (3), banana flour (4), cassava flour (5), and corn flour (6), for 30 days. The malnutrition groups received a diet with protein deficiency for 15 days, then were treated with a diet according to each treatment group. The liver enzymes were analyzed, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Furthermore, the liver's histopathological changes in each group were evaluated using Hematoxylin eosin staining. Results: The AST levels in malnourished male rats significantly (p&lt;0.05) increased (240.75±67.23 U/L) compared to the control group (170.00±33.52 U/L). While, the ALT levels (66.75±12.69 U/L) were decreased compared to the control group (98.75±26.61 U/L). Furthermore, malnutrition diet in rats caused significant changes in liver histology, including inflammatory cell infiltration, necrosis, congestion of the central vein, cytoplasmic vacuolization, and widened hepatic sinusoid. Interestingly, normalized AST and ALT levels and improved liver histology were observed in malnourished rats after receiving normal feed and flour of banana, cassava, and corn. Conclusions: Banana, cassava, and corn flours exhibited hepatoprotective activity on malnutrition-induced hepatotoxicity in malnourhised male rats.

Integrated transcriptomics and proteomics analyses reveal the ameliorative effect of hepatic damage in tilapia caused by polystyrene microplastics with chlorella addition

Fish exhibit varying responses to polystyrene microplastics (MPs) depending on particle size. Previous studies suggested that microorganisms adhering to the surface of MPs can induce toxic effects. In this study, Tilapia were exposed to MPs of control (group A), 75 nm (B), 7.5 μm (C), 750 μm (D), as well as combinations of all sizes (E) and 75 nm MPs with Chlorella vulgaris addition (F) for 7, 10 and 14 days. Histopathological changes in liver of tilapia were assessed using enzyme activities, transcriptomics and proteomics. The results showed that in groups combined MPs of different particle sizes and those supplemented with chlorella, MPs were localized on the surface of goblet cells, leading to vacuoles, constricted hepatic sinuses and nuclei displacement. Exposure to 7.5 and 750 μm MPs significantly increased the contents of fatty acid synthase (FAS), adenosine triphosphate (ATP), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), total cholesterol (TC), total triglyceride (TG) contents at 7 and 10 days. In particular, cytochrome p450 1a1 (EROD), reactive oxygen species (ROS) and superoxide dismutase (SOD) were markedly elevated following exposure to MPs. Apoptotic markers caspase-3, and inflammatory markers, including tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β), had a similar upward trend in comparisons of group C vs A at 7 d, group D vs A at 14 d. The peroxisome proliferator activated receptor (PPAR) signaling pathway, spliceosome, was highly enriched during the 7-day exposure of medium sized MPs, while largest MPs in the comparison of group D vs A at 14 d activated pathways such as phagosome, apoptosis, salmonella infection. Transcriptomic analysis revealed that after 14 days, the kyoto encyclopedia of genes and genomes (KEGG) pathways associated with protein processing in endoplasmic reticulum and the PPAR signaling has been significantly enriched in the Chlorella-supplemented group, which was further confirmed via the proteomic analysis. Overall, the findings highlight the size-dependent effects of MPs on histopathological changes, gene and protein expression in the liver of tilapia, and C. vulgaris effectively attenuated liver damages, likely through modulation of endoplasmic reticulum protein processing and PPAR signaling pathways.

Supplementation with cysteine improved metabolic syndrome in rats by increasing antioxidant potential in the liver and adipose tissue, as well as decreasing hepatic NF-κB expression

Insulin resistance is a key characteristic of metabolic syndrome (MetS). The hepatic nuclear factor- κB (NF-κB) signaling pathway plays a crucial role in insulin resistance and the development of type 2 diabetes. Our study aimed to examine the impact of cysteine (Cys) on various biochemical and histopathological parameters in the liver and kidney, hepatic NF-kβ expression, oxidative stress, inflammation, glycation, carbonyl stress markers, and insulin resistance. The study involved four groups of rats, each consisting of seven rats: a control group, a MetS group, and two similar groups receiving Cys treatment. Metabolic syndrome was induced in rats by administering a 40% sucrose solution, while, the treated groups received 50 mg/L Cys in their drinking water. Various factors, including body weight, hepatic NF-kβ expression, levels of antioxidants, anti-glycation, oxidative stress, carbonyl stress, inflammatory, anti-glycation, and glycation markers were assessed in blood and tissues. Liver and kidney function parameters and metabolic profiles were measured. Finally, liver tissue was also evaluated by a pathologist. The results showed that Cys reduced hepatic NF-kβ expression, oxidative stress, inflammation, glycation and carbonyl stress markers, as well as liver fatty content, blood sugar levels, insulin resistance, cardiovascular risk index, and body weight. The treatment also mitigated histopathological liver changes and acute hepatitis (p < 0.001). Cysteine exhibited anti-obesity and anti-atherosclerotic effects, improved β-cell function, insulin sensitivity, and lipid metabolism, and enhanced liver and kidney function, as well as prevented acute hepatitis by restoring the GSH/GSSG ratio, hepatic NF-kβ signaling, and carbonyl stress.

Investigating the Protective Effects of Ascorbic Acid Against Paracetamol-induced Liver Toxicity in Wistar Rats

Paracetamol is one of the most widely used analgesics and antipyretics but can cause severe liver damage at high doses. This study explores the potential protective effects of ascorbic acid (vitamin C) against paracetamol-induced hepatotoxicity in Wistar rats. For this experimental study, 25 mature male Wistar rats, weighing 140–180g, were divided into five groups: Group 1 stands for the Normal Control. Group 2 received 25 mg of PCM for 21 days, whereas Group 3 received 500 mg of ascorbic acid. Furthermore, after PCM was given, rats in groups 4 and 5 were given 500 mg and 1000 mg of ascorbic acid, respectively. Following PCM and Ascorbic acid treatment, biochemical parameters and histoarchitectural studies were examined. Histopathological examination of liver tissue was performed to evaluate cellular architecture and damage. Results indicated that treatment with ascorbic acid significantly mitigated the elevation of liver enzymes and histopathological changes compared to the paracetamol-only group. In conclusion, the research underscores the potential role of ascorbic acid in safeguarding liver function.

Eriodictyol regulates white adipose tissue browning and hepatic lipid metabolism in high fat diet-induced obesity mice via activating AMPK/SIRT1 pathway

Ethnopharmacological relevanceBlossom of Citrus aurantium L. var. amara Engl. (CAVA) has been popularly consumed as folk medicine and dietary supplement owing to its various beneficial effects and especially anti-obesity potential. Our previous study predicted that eriodictyol was probably one of the key active compounds of the total flavonoids from blossom of CAVA. However, effects of eriodictyol in anti-obesity were still elusive. Aim of the studyThis study was performed to explore the precise role of eriodictyol in white adipose tissue (WAT) browning and hepatic lipid metabolism, and simultaneously, to verify the impact of eriodictyol on the total flavonoids of CAVA in losing weight. Materials and methodsThe pancreas lipase assay was conducted and oleic acid-induced HepG2 cells were established to preliminarily detect the lipid-lowering potential of eriodictyol. Then, high fat diet-induced obesity (DIO) mouse model was established for in vivo studies. The biochemical indicators of mice were tested by commercial kits. The histopathological changes of WAT and liver in mice were tested by H&E staining, Oil Red O staining and Sirius Red staining. Immunohistochemical, western blot assay, as well as RT-qPCR analysis were further performed. Additionally, molecular docking assay was used to simulate the binding of eriodictyol with potential target proteins. ResultsIn vitro studies showed that eriodictyol intervention potently inhibited pancreatic lipase activity and reversed hepatic steatosis in oleic acid-induced HepG2 cells. Consistently, long-term medication of eriodictyol also effectively prevented obesity and improved lipid and glucose metabolism in diet-induced obesity (DIO) mice. Obesity-induced histopathological changes in iWAT, eWAT and BAT, and abnormal expression levels of IL-10, IL-6 and TNF-α in iWAT of DIO mice were also significantly reversed by eriodictyol treatment. Eriodictyol administration significantly and potently promoted browning of iWAT by increasing expression levels of thermogenic marker protein of UCP1, as well as brown adipocyte-specific genes of PGC-1α, SIRT1 and AMPKα1. Further assays revealed that eriodictyol enhanced mitochondrial function, as shown by an increase in compound IV activity and the expression of tricarboxylic acid cycle-related genes. Besides, eriodictyol addition markedly reversed hepatic damages and hepatic inflammation, and enhanced hepatic lipid metabolism in DIO mice, as evidenced by its regulation on p-ACC, CPT1-α, UCP1, PPARα, PGC-1α, SIRT1 and p-AMPKα expression. Molecular docking results further validated that AMPK/SIRT1 pathway was probably the underlying mechanisms by which eriodictyol acted. ConclusionEriodictyol exhibited significant anti-obesity effect, which was comparable to that of the total flavonoids from blossom of CAVA. These findings furnished theoretical basis for the application of eriodictyol in weight loss.

β-arrestin2 promotes angiogenesis of liver sinusoidal endothelial cells through the VEGF/VEGFR2 pathway to aggravate cirrhosis

Excessive extracellular matrix deposition and increased intrahepatic angiogenesis are prominent features of cirrhosis. β-arrestin2 is thought to be involved in the pathological processes of various fibrotic diseases. This study aimed to investigate the role and possible mechanism of β-arrestin2 in the angiogenesis of cirrhosis. Firstly, β-arrestin2 expression in liver tissues of cirrhotic patients was detected, and the correlation between β-arrestin2 and α-SMA, CD-31, PDGF, and VEGF indexes was analyzed. Then, after liver cirrhosis induced by CCL4 in Arrb2-KO mice (β-arrestin2 coding gene), liver histopathological changes were observed, and the expressions of α-SMA, CD-31, PDGF, VEGF, and VEGFR2 were detected. Finally, VEGF-A was used to treat human liver sinusoidal endothelial cells (LSECs) to simulate pathological conditions. After transfection with si-ARRB2, the cell activity, MDA and GSH-PX activities, cell invasion, angiogenesis, and the expressions of α-SMA, CD-31, and VEGF/VEGFR2 pathway were detected. Results showed that β-arrestin2 expression in the liver increased significantly during cirrhosis and was positively correlated with angiogenesis. In vivo, Arrb2-KO significantly inhibited fibrosis and angiogenesis in cirrhotic mice, and decreased the expressions of α-SMA, CD31, PDGF, VEGF, and VEGFR2. Studies using LSECs in vitro showed that after intervention of ARRB2, the activity of LSECs and the number of invasions and tubule formations were significantly reduced. Similarly, after transfection with si-ARRB2, the expressions of α-SMA, CD31, PDGF, VEGF, and VEGFR2 in LSECs were significantly decreased. Collectively, β-arrestin2 aggravated cirrhosis by promoting the angiogenesis of LSECs. Blocking β-arrestin2 may be an important target against angiogenesis and fibrosis in cirrhosis.

Thymol Protects against 5-Fluorouracil-Induced Hepatotoxicity via the Regulation of the Akt/GSK-3β Pathway in In Vivo and In Silico Experimental Models.

5-fluorouracil (5-FU) is a widely used, highly effective chemotherapeutic agent. However, its therapeutic efficacy is often limited by associated adverse effects, with hepatotoxicity being frequently reported with 5-FU therapy. Thymol is a monoterpene found in thyme (Thymus vulgaris L., Lamiaceae) and is known for its antioxidant, anti-apoptotic, and anticancer activities. This study aimed to explore the hepatoprotective activity of thymol against 5-FU-induced liver injury. Rats received two intraperitoneal doses of 5-FU (150 mg/kg) either alone or in combination with thymol at doses of 60 mg/kg or 120 mg/kg. Liver enzymes, oxidative stress, and apoptotic markers, in addition to histopathological changes, were assessed. 5-FU induced marked liver injuries as evidenced by elevated liver enzymes and histopathological changes, in addition to abnormalities of oxidative and apoptotic markers. The administration of thymol ameliorated the 5-FU-induced oxidative damage through increasing hepatic antioxidants and lowering lipid peroxidation. Apoptotic response markers such as Bax, Bcl-2, Bax/Bcl-2 ratio, and PARP were also improved. Furthermore, Western blotting analysis showed that thymol modulated the 5-FU-induced changes in the expression of Akt/GSK-3β and p44/42 MAPK (ERK1/2) signaling pathways. Our research is the first to shed light on thymol's potential protective effect against 5-FU- induced hepatotoxicity by inhibiting oxidative and apoptotic pathways and modulating the Akt/ GSK-3β as well as p44/42 MAPK (ERK1/2) signaling pathways.

Effects of the Aquatic Extract of Cinnamon Zeylanicum on STZ-Induced Diabetic Rats: A Molecular and Histopathological Study

Background: The prevalence of diabetes mellitus has increased over the past few decades, making it a significant public health challenge of the twenty-first century. Cinnamon, as a traditional medicine, has been used in several regions of the world for its anti-diabetic properties. Objectives: The current study was conducted to determine the effect of Cinnamon Zeylanicum extract on blood glucose levels, oxidative stress markers, and antioxidant enzyme gene expression in diabetic rats. Methods: Forty Sprague-Dawley rats were divided into four groups, each containing 10 rats. A single dose of streptozotocin (50 mg/kg, IP) was used to induce diabetes. In this investigation, 40 mg/kg body weight of cinnamon extract was administered orally. After eight weeks, the levels of glucose, malondialdehyde (MDA), and reduced glutathione (GSH) were determined using biochemical methods. Additionally, the expression levels of catalase and glutathione reductase in the rat liver homogenate were evaluated using real-time PCR. The effect of cinnamon extract on histopathological changes in the rats' liver was also investigated. Results: The findings indicated that the administration of cinnamon extract resulted in a considerable reduction in blood glucose (210 ± 29.9 vs. 449 ± 48.4 mg/dL; P &lt; 0.001) and liver MDA levels (2.01 ± 0.35 vs. 3.05 ± 0.47; P &lt; 0.001) in diabetic rats after eight weeks. However, this extract had no significant effect on GSH levels (4.71 ± 0.25 vs. 4.75 ± 0.42; P = 0.79) in diabetic rats compared to diabetic control rats. The mRNA expression of catalase and glutathione reductase genes in the liver of diabetic control rats (0.73 ± 0.23 and 0.90 ± 0.18, respectively) was significantly lower than that of the healthy control group (1.33 ± 0.37 and 1.46 ± 0.54, respectively) (P = 0.001, P = 0.012). Administration of cinnamon extract increased the expression levels of these antioxidant enzyme genes, but these changes were statistically not significant (P = 0.72 and P = 0.48, respectively). Furthermore, the creation of hyperglycemia led to slight hypertrophic degeneration and lymphocyte infiltration in hepatocytes. Notably, the administration of cinnamon extract was unable to reverse these abnormalities. Conclusions: The findings of our study support cinnamon's anti-diabetic and antioxidant properties in diabetic rats. However, the histological abnormalities in the diabetic rats' livers could not be altered by the administration of cinnamon.

Hepatoprotective potential of taxifolin in type 2 diabetic rats: modulation of oxidative stress and Bcl2/Bax/Caspase-3 signaling pathway.

Diabetes mellitus (DM) is a global metabolic problem. Several factors including hyperglycemia, oxidative stress, and inflammation play significant roles in the development of DM complications. Apoptosis is also an essential event in DM pathophysiology, -with B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) determining apoptotic susceptibility. The present study aimed to elucidate the protective effects of two doses of taxifolin (TXF) on liver damage in diabetic rats and explore the possible mechanisms of action. DM was induced in eighteen rats through intraperitoneal injections of 50mg/kg streptozotocin and 110mg/kg nicotinamide. Diabetic rats received daily oral intubation of 25 and 50mg/kg TXF for 3 months. In the untreated diabetic group, there was a significant increase in fasting and postprandial glucose levels, glycosylated hemoglobin A1C (HbA1c), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), while insulin and adiponectin levels decreased significantly. Both TXF doses mitigated hyperglycemia, regulated cytokine production, and increased insulin level. Gene expressions and protein levels of Bax, caspase 3, and cytochrome c were significantly increased, while Bcl-2 was significantly decreased in the livers of diabetic rats, effects that were significantly ameliorated after TXF treatment. The results of the TUNEL assay supported the apoptotic pathway. Additionally, TXF significantly decreased lipid peroxidation and enhanced antioxidant enzyme activity in diabetic rats. Liver enzymes and histopathological changes also showed improvement. TXF mitigated diabetes-associated hepatic damage by reducing hyperglycemia, oxidative stress, inflammation, and modulating anti-/pro-apoptotic genes and proteins. A dose of 50mg/kg TXF was more effective than 25mg/kg and is recommended for consumption.

Ameliorative Potential of Ginger for Mitigating Liver Damage Caused by Fluopyram in Male Albino Rats

Fluopyram is a widely used new generation broad spectrum fungicide and a variety of biochemical and histopathological alterations in the livers of albino rats. These include inflammatory cells, dilated sinusoids, haemorrhage, dilation of central veins, congestion and presence of erythrocytes. Significant increase in blood alanine aminotransferase (ALT), aspartate amino transferase (AST), acid phosphatise (ACP) and decrease in alkaline phosphatise (AKP) enzyme levels were seen in high dose of fluopyram treated rats as compared to control. The oxidative stress and antioxidant enzymes showed a significant reduction in superoxide dismutase (SOD), catalase (CAT) and increase in malondialdehyde (MDA) level. Rats treated with fluopyram and ginger showed improved histopathological changes in liver. Ginger extract also showed decreased serum levels of malondialdehyde and raised serum levels of antioxidant enzymes. According to the current study, strong antioxidant activity of ginger mediates its protective effect against fluopyram induced liver damage.

Toxicological Assessment of Azo Dye Brown HT In Vivo

Background: Azo dyes, widely used in food, pharmaceuticals, textiles, and cosmetics, raise significant safety concerns due to their potential toxicological effects. Specifically, the biotransformation of azo dyes into aromatic amines, which may have carcinogenic potential, necessitates an investigation into their impact on health, especially for vulnerable populations like children. Methods: This study assessed the effects of Brown HT (E155) azo dye on juvenile rats. Male Long-Evans rats were divided into control and treatment groups, receiving varying doses of Brown HT over six weeks. Parameters measured included body weight, hematological and biochemical indices, and histopathological changes in liver and kidney tissues. Results: The results indicated a significant dose-dependent effect of Brown HT on body weight, blood parameters, and organ function. The high-dose group exhibited significant weight reduction, elevated liver enzymes, and abnormal lipid profiles. Histopathological examination revealed severe liver damage and renal impairment in high-dose groups, indicating potential long-term health risks associated with azo dye consumption. Conclusion: Brown HT azo dye demonstrates dose-dependent toxicity in juvenile rats, impacting physiological, biochemical, and histopathological parameters. These findings underscore the need for regulatory scrutiny regarding azo dye usage in food products, particularly for children, to mitigate associated health risks and promote safer food practices.

TDMPP activation of estrogen receptor 2a regulates smc2 and p53 signaling to interfere with liver development in zebrafish (Danio rerio)

Tris (2,6-dimethylphenyl) phosphate (TDMPP), a novel organic phosphorus flame retardant (OPFR), has been found to have estrogenic activity. Estrogens are critical in regulating various biological responses during liver development. However, the effects of TDMPP on zebrafish liver development remain largely unexplored. Here, we utilized a chemical genetic screening approach to assess the estrogenic effects of TDMPP on liver development and to elucidate the underlying molecular mechanism. Our findings revealed that zebrafish larvae exposed to environmentally relevant concentrations of TDMPP (0.05 and 0.5 μM) exhibited concentration-dependent liver impairments, including reduced liver size, histopathological changes, and hepatocyte apoptosis. In addition, E2 caused similar adverse effects to TDMPP, but the pharmacological blockade of estrogen synthesis alleviated the effects on liver development. Chemical inhibitors and morpholino knockdown assays indicated that the reduction of esr2a blocked TDMPP-induced liver impairments, which was further confirmed in the esr2a-/- mutant line. Subsequently, transcriptomic analysis showed that the estrogen receptor activated by TDMPP inhibited the expression of smc2, which was linked to the suppression of liver development through p53 activation. Consistently, overexpression of smc2 and inhibition of p53 evidently rescued hepatic damages induced by TDMPP. Taken together, the above findings identified esr2a, downstream smc2, and p53 as important regulators for the estrogenic effects of TDMPP on liver development. Our work fills crucial gaps in the current knowledge of TDMPP's hepatotoxicity, providing new insights into the adverse effects of TDMPP and the molecular mechanisms of action. These findings underscore the need for further ecological risk assessment and regulatory considerations.

“Adjusting internal organs and dredging channelon” electroacupuncture glycolipid metabolism disorders in NAFLD mice by mediating the AMPK/ACC signaling pathway

To investigate the effect mechanism of electroacupuncture based on the AMP-activated protein kinase (AMPK) /acetyl-CoA carboxylase (ACC) signaling pathway to improve glycolipid metabolism disorders in db/db mice. 10 db/m mice with normal genotype were used as the normal control group without diabetes (Con), and 30 db/db mice were divided randomly into three groups: Pathological model mice (Mod), Acupuncture + ACC antagonist group (Acu + ACC), and Acupuncture + AMPK antagonist group (Acu + AMPK). Con and Mod did not receive any special treatment, only as a control observation. The latter two groups of mice received electroacupuncture treatment for 4 weeks. Mouse triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol(LDL-C), and cholesterin(CHO) levels were detected by colorimetric assay. Enzyme-linked immunoassay (ELISA) was used to detect insulin(INS) levels. Liver histopathologic changes and hepatic glycogen synthesis were observed by HE and PAS staining. The mRNA and protein expression of insulin receptor substrate-1(IRS1), Phosphatidylinositol 3-kinase(PI3K), protein kinase B (AKT), AMPK, and ACC were detected by Western blot and qRT-PCR.The results show that compared with Mod, TG, LDL, CHO, and INS levels of Acu + AMPK and Acu + ACC mice were significantly reduced (P < 0.05), and the HDL levels were significantly increased (P < 0.05), the steatotic degeneration of mice hepatocytes was reduced to different degrees, and the hepatocyte glycogen particles were increased, and the latter two groups had a decrease in AKT, ACC mRNA expression was reduced (P < 0.05), PI3K protein expression was increased, and AKT and ACC protein expression was reduced (P < 0.05), in addition, protein expression of AMPK was increased and IRS1 protein expression was reduced in Acu + ACC (P < 0.05). The study showed that electroacupuncture improves glucose-lipid metabolism disorders in db/db mice, and this mechanism is related to the AMPK/ACC signaling pathway.

Emodin alleviates cholestatic liver injury by modulating Sirt1/Fxr signaling pathways

Emodin (EMO) has the effect of anti-cholestasis induced by alpha-naphthylisothiocyanate (ANIT). But its mechanism is still unclear. The farnesoid X receptor (Fxr) is the master bile acid nuclear receptor. Recent studies have reported that Sirtuin 1 (Sirt1) can regulate the activities of Fxr. The purpose of the current study was to investigate the mechanism of EMO against ANIT-induced liver injury based on Sirt1/Fxr signaling pathway. The ANIT-induced cholestatic rats were used with or without EMO treatment. Serum biochemical indicators, as well as liver histopathological changes were examined. The genes expressions of Sirt1, Fxr, Shp, Bsep and Mrp2 were detected. The expressions of Sirt1, Fxr and their downstream related genes were investigated in vitro. The results showed that EMO significantly alleviated ANIT-induced liver injury in rats, and increased Sirt1, Fxr, Shp, Bsep and Mrp2 gene expression in liver, while decreased the expression of Cyp7a1. EMO significantly activated Fxr, while Sirt1 inhibitor and Sirt1 gene silencing significantly reduced Fxr activity in vitro. Collectively, EMO in the right dose has a protective effect on liver injury induced by ANIT, and the mechanism may be through activation of Fxr by Sirt1, thus regulating bile acid metabolism, and reducing bile acid load in hepatocytes.