Rat Liver Tissue Research Articles

Therapeutic effect of fecal microbiota transplantation on rats with liver cirrhosis and its influence on gut microbiota.

This study aimed to explore the therapeutic effect of fecal microbiota transplantation (FMT) on liver cirrhosis-induced rat models by studying changes in intestinal flora distribution and liver pathology. Cirrhosis was induced in adult male Sprague-Dawley rats using carbon tetrachloride; successful establishment of the cirrhosis model was verified using hematoxylin and eosin (HE) staining. Rats were divided into normal control, cirrhosis model+normal saline, and cirrhosis model+FMT groups. Fecal intestinal flora was analyzed using 16S rRNA high-throughput sequencing for each group. Alpha diversity, beta diversity, and functional prediction analyses were performed. Additionally, rat liver tissue was subjected to HE staining to compare the degree of fibrosis and liver damage between the groups. FMT significantly improved the diversity, richness, and uniformity of the intestinal flora in rats with liver cirrhosis. Notably, post-FMT, the abundance of lactobacillaceae, bacilli, and bacteroidia increased, while the abundance of clostridia decreased. Moreover, hepatic fibrosis improved after FMT. The dysbiosis of intestinal flora in rats with liver cirrhosis improved after FMT. Thus, FMT can regulate intestinal flora, reduce liver inflammation, and improve hepatic fibrosis and cirrhosis.

Laser capture microdissection and native mass spectrometry for spatially-resolved analysis of intact protein assemblies in tissue.

Previously, we have shown that native ambient mass spectrometry imaging allows the spatial mapping of folded proteins and their complexes in thin tissue sections. Subsequent top-down native ambient mass spectrometry of adjacent tissue section enables protein identification. The challenges associated with protein identification by this approach are (i) the low abundance of proteins in tissue and associated long data acquisition timescales and (ii) irregular spatial distributions which hamper targeted sampling of the relevant tissue location. Here, we demonstrate that these challenges may be overcome through integration of laser capture microdissection in the workflow. We show identification of intact protein assemblies in rat liver tissue and apply the approach to identification of proteins in the granular layer of rat cerebellum.

Effects of repeated doses of paracetamol administration during pregnancy on lung, kidney, and liver tissues of pregnant rats.

Paracetamol is one of the most widely used analgesics and antipyretics in the world. It is the most commonly used analgesic and antipyretic agent in pregnancy. Paracetamol is known to have toxic effects on the liver, lung, and kidney. In this study, we investigated the effects of long-term chronic paracetamol exposure on the lung, liver, and kidney in newborn rats at different trimesters of pregnancy. In our study, we formed control (group C), first trimester (group A), and third trimester (group B) groups. Group A had the first seven days of pregnancy and group B had days 15-21. Paracetamol was given orally during the specified periods. On the third postnatal day, pups were euthanized by applying 50 mg/kg ketamine intraperitoneally, and then lung, liver, and kidney tissues were kept under appropriate conditions for examination. A total of 70 pups underwent histopathological examination. The lung revealed congestion (p<0.0001), and erythrocytes (p<0.0001), the liver revealed significant histopathological findings in terms of the presence of inflammation (p<0.0001), vacuolar degeneration (p<0.0001), and sinusoidal dilatation in groups A and B compared to the control group under light microscopy. MDA and free radical metabolism enzyme activities, CAT, GSH, and SOD were evaluated. While there were no significant differences between the groups in lung and kidney tissues, oxidant parameters were significant in liver tissues. Our data point out that subacute doses of paracetamol used chronically in different trimesters caused damage to the lung, liver, and kidney tissues of pups.

Identification of Proteomic Biomarkers of Acetaminophen-Induced Hepatotoxicity Using Stable Isotope Labeling.

Quantitative proteomics approaches based on stable isotopic labeling and mass spectrometry have been widely applied to disease research, drug target discovery, biomarker identification, and systems biology. One of the notable stable isotopic labeling approaches is trypsin-catalyzed 18O/16O labeling, which has its own advantages of low sample consumption, simple labeling procedure, cost-effectiveness, and absence of chemical reactions that potentially generate by-products. In this chapter, a protocol for 18O/16O labeling-based quantitative proteomics approach is described with an application to the identification of proteomic biomarkers of acetaminophen (APAP)-induced hepatotoxicity in rats. The protocol involves first the extraction of proteins from liver tissues of control and APAP-treated rats and digestion into peptides by trypsin. After cleaning of the peptides by solid-phase extraction, equal amounts of peptides from the APAP treatment and the control groups are then subject to trypsin-catalyzed 18O/16O labeling. The labeled peptides are combined and fractionated by off-line strong cation exchange liquid chromatography (SCXLC), and each fraction is then analyzed by nanoflow reversed-phase LC coupled online with tandem mass spectrometry (RPLC-MS/MS) for identification and quantification of differential protein expression between APAP-treated rats and controls. The protocol is applicable to quantitative proteomic analysis for a variety of biological samples.

Alterations of serum biochemical parameters and tyrosine phosphorylation in kidney and liver of chronic stress-induced rats

Abstract Chronic stress (CS) can contribute to dysfunction in several organs including liver and kidney. This study was performed to investigate the changes in serum biochemistry, histological structure, as well as in localization of tyrosine phosphorylated proteins (TyrPho) and Heat shock protein 70 (Hsp-70) in liver and kidney tissues of CS rats induced by two stressors (restrained and force swimming) for 60 consecutive days. Samples of blood, liver, and kidney were collected from adult male Sprague–Dawley rats in each group. Our results showed that serum biochemical parameters including corticosterone, blood sugar, urea nitrogen, creatinine, cholesterol, triglyceride, HDL-C, LDL-C, ALT, AST, alkaline phosphatase in CS group were significantly different from that in normal group in both liver and kidney tissues. Although histological structure was not changed. TyrPho expression was significantly increased in liver lysate but significantly decreased in kidney. Hsp-70 expression in liver increased whereas in kidney decreased. In conclusion, CS can induce changes in liver and kidney functions.

Ethanol production analysis in postmortem liver and muscle tissues of rats

Ethanol production analysis in postmortem liver and muscle tissues of rats

Antioxidant effect of Rosa pimpinellifolia L. fruit extract on cholestatic liver injury: an experimental study.

Antioxidants have been considered a rational curative strategy to prevent and cure liver diseases involving oxidative stress. An acute obstructive jaundice rat model was established to investigate the in vivo hepatoprotective efficacy of Rosa pimpinellifolia L. The experimental jaundice model was performed by binding the main bile duct in 25 male Sprague-Dawley rats. All rats were randomly divided into five groups: first group: laparotomy-sham-only, second group: biliary tract binding (control), and third, fourth, and fifth groups: treatment groups with 250, 500, and 750 mg/kg fruit extracts daily, respectively. Considering dosage, although there was no significant therapeutic effect in the 250 mg/kg of Rosa pimpinellifolia L. group, the best results were found in the 500 mg/kg dose group, while results in the 750 mg/kg dose group showed consistent correlation with proinflammatory response. With regard to biochemical parameters, lipid hydroperoxide level in the rat serum and liver tissue was significantly decreased in all treatment groups. Amadori products, which are one of the early markers of glycol-oxidative stress, showed statistical significance in the treatment. It was revealed that the antioxidant effect of Rosa pimpinellifolia L. was more prominent in the early stages of hepatic injury secondary to oxidative stress.

The effect of aerobic exercise and ethanolic extract of rice bran on the expression of Acetyl-CoA Carboxylase and HMGCR genes in the liver tissue of rats fed with a high-fat diet

The effect of aerobic exercise and ethanolic extract of rice bran on the expression of Acetyl-CoA Carboxylase and HMGCR genes in the liver tissue of rats fed with a high-fat diet

Hepatoprotective effect of Nobiletin against 5-fluorouracil induce hepatotoxicity

5-florouracil is a widely used anticancer/anti-metabolite drug used to treat solid tumor like colon cancer, head and neck, rectum, stomach, pancreas and breast cancer; but, it can cause hepatotoxicity by induction of apoptosis through activation of caspases enzymes and oxidative stress. Nobiletin is a citrus fruit-derived flavonoid that possess significant biological activity, including anticancer, and anti-inflammatory. This study was design to investigate the effects of nobiletin against 5-florouracil-indcued hepatotoxicity in male rats through the measurement of selected -inflammatory, -apoptosis, and -oxidative stress markers. By use male Albino rats weighing 150-250gm around 28 animals; giving them tap water ad libitum and fed commercial pellets; and randomized into four groups (7animals/group) as following arrangement: Group I oral administered only corn oil for rats 1 ml for each kilogram for day by using of oral gavage for rat for 14 days. Group II: oral administered Nobiletin at dose 10 mg for each kilogram for each day (dissolved in corn oil) via oral gavage for 14 days. Group III: oral administered corn oil via oral gavage for 14 days after that single IP injection of 5-FU (150 mg/kg) on the day fourteenth (14). Group VI: Rats oral administered nobiletin dissolved in corn oil daily by oral gavage at a dose 10 mg/kg for each day for 14 days and a single IP injection of (150 mg/kg) 5-florouracil was given on day 14. All groups, seven animals of each group were sacrificed at day fifteenth (15); and, serum was collected to measure inflammatory and anti-inflammatory markers (interlukin-6 and interlukin-10) and liver function tests(ALT, LDH and AST); furthermore, liver tissue samples were collected to measure level of caspase-3, malondialdehyde and reduced form of glutathione, assessment of Hemeoxygenase-1 and NADPH quinone dehydrogenase-1 enzymes. In addition, histopathological study of the liver tissue of rats was perform to detect difference between architecture of liver cells in all rats’ groups. The protective effect of Nobiletin noted by decrease in apoptosis of hepatocytes by decreasing of caspase-3 and reduction on free radical through reduce in malondialdehyde level, also increase in Hemeoxygenase-1gene expression. Increase in NADPH quinone dehydrogenase-1 dehydrogenase enzyme. On histopath reduce in congestion and some inflammatory infiltration by using of nobiletin prior to give 5-florouracil.

Preclinical Evaluation of Nerolidol’s Hepatoprotective and Nephroprotective Potential

Background: Due to the potential negative effects of artificial food additives on health and the recent surge in consumer awareness of the issue, natural goods are becoming more and more popular in diets. Objective: The main objective of the current study is the evaluation of the protective effect and antioxidant role of Nerolidol against alloxan-induced oxidative stress, hepatotoxicity, and nephrotoxicity. Method: The present experiment was designed as Group I (control), Group II (Alloxan monohydrate, 120 mg/kg i.p), Group III (Ascorbic acid 250 mg/kg p.o), Group IV (Nerolidol 100 mg/kg p.o), Group V (Nerolidol 200 mg/kg p.o), Group VI (Nerolidol 300 mg/kg p.o). Alloxan was given to all groups excluding control group in order to induce hepatorenal toxicity. The groups III, IV, V and VI received the Standard Ascorbic acid and Nerolidol after 72 hrs. of alloxan administration for consecutive 14 days. The protective roles and antioxidant activity of Nerolidol against Alloxan induced oxidative stress and hepatorenal toxicity were evaluated by histopathological changes, measuring hepatic and renal damage biomarkers, antioxidant enzyme levels and malondialdehyde (MDA) parameters in the liver and kidney tissues of rats. Result and Conclusion: The biochemical analysis showed a decrease in serum AST, ALT, ALP, and LDH enzymes, total protein, creatinine, bilirubin, and urea in group III and test groups compared to that of group II. Nerolidol also restored the Alloxan-induced MDA and antioxidant enzyme level to control. Hepatorenal protection of Nerolidol was confirmed by almost normal histological findings in test groups.

The Effect of Single Clove Garlic Extract (Allium sativum) Against Aspartame-Induced Hepatotoxicity in Diabetic Rats

Background: Aspartame is a widely used synthetic sweetener used for dietary control and by diabetics. Objectives: This study aims to investigate the effect of a single garlic clove extract against aspartame-induced hepatotoxicity in diabetic rats. Methods: Forty-eight experimental male albino rats were randomly divided into eight groups (6 rats per group) as follows: Group (G)1: served as normal control and received distilled water orally, G2: rats treated with single clove garlic (SCG) extract (0.5 g/kg body weight), G3: rats were treated with SCG extract (0.5 g/kg body weight) and alkaline phosphatase (ALP) (200 mg/kg body weight), G4: rats treated with ASP (200 mg/kg body weight), G5: was the diabetic control group (induced by alloxan (ALX) 120 mg/kg body weight), G6: diabetic rats were treated with SCG extract (0.5 g/kg body weight), G7: diabetic rats were treated with SCG extract (0.5 g/kg body weight) and ASP (200 mg/kg body weight) and G8: diabetic rats were treated with ASP 200 mg/kg body weight. Results: The results obtained showed that treatment with ASP caused a significant increase in serum levels of serum alanine transaminase (ALT), aspartate transaminase (AST), and ASP in SCG extract-treated rats in G3 and G4 and diabetic rats in G7 and G8, while treatment with SCG extract caused a significant decrease in serum levels of ALT, AST and ALP in SCG treated rats in G2 and G6 and diabetic rats in G7 compared to the control group (G1). After treatment with ASP, histologic changes in the liver were observed in G4, which were more pronounced in G8, indicating liver damage compared to the control group, while treatment with SCG extract showed further changes in liver tissue in the diabetic rats of G7 and G8. Conclusion: The present study suggests that administering ASP in normal rats leads to liver dysfunction. Moreover, our results proved that the application of ASP in diabetic rats may cause additional damage compared to ASP in normal rats. This study demonstrated that treatment with SCG extract significantly attenuated the biochemical and histopathologic changes induced by ASP and alloxan. From the data obtained, it appears that treatment with SCG extract has a protective effect against the toxicity of ASF and alloxan on the liver of normal and diabetic rats.&#x0D;

Application of Several Special Staining Methods for Paraffin Sections on Epon-Embedded Semithin Sections

Aim: This study aimed to compare several specific staining protocols recommended for paraffin sections and toluidine blue and light green double staining combination to be tried for the first time with routine toluidine blue staining on semithin epon sections.&#x0D; Material and Methods: Samples of 1x1x1 mm were taken from the liver, skin, and aorta tissues of Wistar albino adult rats. Tissue samples were fixed with 5% glutaraldehyde at +4º C overnight, postfixed with 1% osmium tetroxide for one hour, and then, blocked with Epon 812 after processing. Semithin sections of 1 μm thickness were obtained from the epon blocks. Sections were stained with Altmann’s method (for mitochondria), Verhoeff’s method (for elastic fibers), Gordon&amp;Sweets’ silver impregnation method (for type III collagen), toluidine blue and light green double staining combination (for type I collagen) and routine toluidine blue method.&#x0D; Results: In liver sections, mitochondria in hepatocytes were differentiated by the Altmann method, and stromal type III collagen fibers were distinguished with Gordon&amp;Sweets’ method. Elastic lamellar structures were easily observed in black in the aortic sections stained with the Verhoeff method. Successful results were obtained in the staining of dermal type I collagen with toluidine blue and light green double staining in skin sections.&#x0D; Conclusion: Since the specific staining tried for the first time gave positive results in epon sections, it was concluded that these methods can be used to determine the localization of cellular and intercellular components that are aimed to be examined at the ultrastructural level.

Protective Effect of Pomegranate Juice on Lead Acetate-Induced Liver Toxicity in Male Rats

Objective: Lead has been reported to cause oxidative stress in liver tissues and cause histopathological changes. Studies have shown that pomegranate juice has antioxidant properties that prevent oxidative stress. In this study, the harmful effects of lead acetate on rat liver tissue and the efficacy of pomegranate juice against these effects were investigated. Methods: 28 male Wistar albino rats were divided into four groups: control, lead acetate (50 mL/kg), pomegranate juice (1 mL/kg), and lead acetate + pomegranate juice (50 mL/kg+1 mL/kg). Lead acetate and pomegranate juice were administered orally. Results: When compared with the control group, it was seen that the lead acetate had an increase in the malondialdehyde level and a decrease in reduced Glutathione, Glutathione S-transferase, and Carboxylesterases. Group lead acetate + pomegranate juice had a reduction in malondialdehyde level and an increase in Glutathione, Glutathione S-transferase, and Carboxylesterases compared with the group lead acetate. The lead level of group lead acetate + pomegranate juice decreased compared to the group lead acetate. Cellular degeneration and irregular hepatic cords were observed in group lead acetate's liver tissue, and the negative changes were lost in group lead acetate + pomegranate juice. Conclusion: It was observed that pomegranate juice had a protective effect against liver toxicity caused by lead acetate.

Phytochemical constituents of bark essential oils of Cinnamomum zeylanicum Blume and effects on liver tissue of rats

Cinnamomum zeylanicum Blume is an evergreen tropical tree belonging to the Lauraceae family; it is a useful plant in traditional and modern medicines. Essential oils of Cinnamomum zeylanicum were prepared and identified using gas chromatography–mass spectrometry (GC-MS). For histological study 80 adult male rats were employed in this study. It is the same weight (30 ±5 gm) and 75 days in age. The animals were divided into 4 groups, with ten rats in each group. The results indicated that C. zeylanicum bark contained 27 different phytochemical components. The main components included Cinnamaldehyde (2-Propenal, 3-phenyl-) (46.46%), 9-Methoxybicyclo, [6.1.0] nona-2,4,6-triene (31.31%), alpha-, Muurolene (7.14%) and Copaene (1.63%). Sections of livers were examined for histological abnormalities, such as the breakdown of the liver architecture and increased inflammation, in comparison to control samples, some hepatocytes were swollen with pyknotic, large nuclei and dilated sinusoids. As well as in the rats treated with noticed sever congestion of central vein (CV), degeneration and sluggish of endothelial lining larger, Bile ducts hyperplasia and necrotic hepatocytes. It can be deduced that the main component of cinnamon bark oil is cinnamaldehyde and the liver displayed some tissue changes, including hepatocyte necrosis and the existence of steatosis foci. Histological and cellular changes in liver tissue were dramatically attenuated by C. zeylanicum essential oil.

High Sucrose Diet-Induced Subunit I Tyrosine 304 Phosphorylation of Cytochrome c Oxidase Leads to Liver Mitochondrial Respiratory Dysfunction in the Cohen Diabetic Rat Model.

The mitochondrial oxidative phosphorylation process generates most of the cellular energy and free radicals in mammalian tissues. Both factors play a critical role in numerous human diseases that could be affected by reversible phosphorylation events that regulate the function and activity of the oxidative phosphorylation complexes. In this study, we analyzed liver mitochondria of Cohen diabetes-sensitive (CDs) and Cohen diabetes-resistant (CDr) rats, using blue native gel electrophoresis (BN-PAGE) in combination with mitochondrial activity measurements and a site-specific tyrosine phosphorylation implicated in inflammation, a known driver of diabetes pathology. We uncovered the presence of a specific inhibitory phosphorylation on tyrosine 304 of catalytic subunit I of dimeric cytochrome c oxidase (CcO, complex IV). Driven by a high sucrose diet in both CDr and CDs rats, Y304 phosphorylation, which occurs close to the catalytic oxygen binding site, correlates with a decrease in CcO activity and respiratory dysfunction in rat liver tissue under hyperglycemic conditions. We propose that this phosphorylation, specifically seen in dimeric CcO and induced by high sucrose diet-mediated inflammatory signaling, triggers enzymatic activity decline of complex IV dimers and the assembly of supercomplexes in liver tissue as a molecular mechanism underlying a (pre-)diabetic phenotype.

Lysophosphatidic acid triggers inflammation in the liver and white adipose tissue in rat models of 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 deficiency and overnutrition.

AGPAT2 (1-acyl-sn-glycerol-3-phosphate-acyltransferase-2) converts lysophosphatidic acid (LPA) into phosphatidic acid (PA), and mutations of the AGPAT2 gene cause the most common form of congenital generalized lipodystrophy which leads to steatohepatitis. The underlying mechanism by which AGPAT2 deficiency leads to lipodystrophy and steatohepatitis has not been elucidated. We addressed this question using an antisense oligonucleotide (ASO) to knockdown expression of Agpat2 in the liver and white adipose tissue (WAT) of adult male Sprague-Dawley rats. Agpat2 ASO treatment induced lipodystrophy and inflammation in WAT and the liver, which was associated with increased LPA content in both tissues, whereas PA content was unchanged. We found that a controlled-release mitochondrial protonophore (CRMP) prevented LPA accumulation and inflammation in WAT whereas an ASO against glycerol-3-phosphate acyltransferase, mitochondrial (Gpam) prevented LPA content and inflammation in the liver in Agpat2 ASO-treated rats. In addition, we show that overnutrition, due to high sucrose feeding, resulted in increased hepatic LPA content and increased activated macrophage content which were both abrogated with Gpam ASO treatment. Taken together, these data identify LPA as a key mediator of liver and WAT inflammation and lipodystrophy due to AGPAT2 deficiency as well as liver inflammation due to overnutrition and identify LPA as a potential therapeutic target to ameliorate these conditions.

Ginkgo Biloba Extract Can Antagonize Subchronic Arsenite Exposure-Induced Hepatocyte Senescence by Inhibiting Oxidative Damage and Inflammation in Rats.

A growing body of evidence suggests that long-term arsenic exposure can induce liver injury. Our previous studies have demonstrated that liver injury occurs in arsenic-poisoning patients and arsenic-exposed rats. However, therapeutic targets are still unclear, and there is a lack of effective drugs. This study aimed to investigate the effects of sodium arsenite (arsenite) exposure on hepatocyte senescence and the intervention effect of ginkgo biloba extract in rats. In this study, 24 male Sprague-Dawley rats (weighing 180-200g) were randomized into three groups. The control group received a normal diet, and the arsenic-exposed group was given 10mg/L arsenite for 3months by free drinking along with a normal diet. The ginkgo biloba extract treatment group was consecutively administered EGb761 (10mg/kg, by gavage) for 1month following 2months of arsenite exposure. Our results showed that exposure to 10mg/L arsenite induced narrowing of the hepatic sinus space, enlargement of hepatocytes, and increased multinucleated hepatocytes and inflammatory cell infiltration in rat liver tissue compared with the normal control group. Moreover, 10mg/L arsenite also caused abnormal expression of inflammation-related indices (IL1-β, IL-6, TNF-α), oxidative damage-related indices (SOD, MDA, GPx), and senescence-related proteins (p16, p-p53, E2F1). EGb761 could effectively reduce the pathological damage of liver tissue and antagonize the abnormal expression of liver tissue inflammation and oxidative damage-related indices as well as cellular senescence-related proteins caused by arsenite exposure. Notably, EGb761 reduced the accumulation of arsenic in rat liver tissues. These results suggested that EGb761 could effectively alleviate subchronic arsenic exposure-induced senescence of hepatocytes, which may be achieved partially through inhibiting inflammation and oxidative damage in rats. This study may provide a new therapeutic target for arsenic-induced liver injury.

AUT-M enterosorbent stabilizes glutathione system in vincristine-treated rats with dimethylhydrazine-induced colon cancer

Colorectal cancer is one of the leading causes of mortality in the world. The search for new methods of therapy for this disease that could correct the state of oxidative stress during the development of neoplasms is up to date. The aim of this work was to study the level of reduced glutathione and the activity of glutathione-dependent enzymes in the development of 1,2 dimethylhydrazine-induced colon cancer in rats while treated with vincristine and the use of enterosorbent. To induce carcinogenesis, dimethylhydrazine was administered to male rats subcutaneously for 30 weeks at a dose of 7.2 mg/kg of body weight. The rats with induced colon cancer received entorosorbent per os at a dose of 0.2 g per 100 g of body weight daily for 21 days. After detoxification therapy, the rats were administered cytostatic vincristine daily at a dose of 0.23 mg/kg for 14 days. A decrease in the content of reduced glutathione, the activity of glutathione reductase and glutathione peroxidase in the blood and liver tissue of rats with colorectal cancer was established. The use of enterosorbent­ AUT-M was shown to be effective in stabilizing the indicators of the glutathione system in rats with induced colon cancer. Cytostatic vincristine did not significantly affect the change of the studied indicators, confirming the effectiveness of previous sorption measures. Keywords: blood, colorectal cancer, entorosorbent, glutathione, glutathione peroxidase, glutathione reductase, liver, vincristine

Anti-diabetic mechanism and potential bioactive peptides of casein hydrolysates in STZ/HFD-induced diabetic rats.

Casein hydrolysates have attracted much interest as anti-diabetic food, but their hypoglycemic mechanism and biopeptides are not well understood. This study aimed to explore the anti-diabetic mechanism and potential biopeptides of casein hydrolysates in streptozotocin/high-fat-diet-induced diabetic rats and HepG2 cells. Oral administration of casein hydrolysate prepared with papain-Flavourzyme combination (P-FCH) decreased fasting blood glucose, improved oral glucose tolerance, and reduced HbA1c values in diabetic rats. P-FCH was ineffective in alleviating insulin resistance (homeostasis model assessment and insulin sensitivity index) and enhancing hepatic insulin signaling transduction (phosphorylated Akt, hexokinase activity, and pyruvate kinase activity) in diabetic rats. However, P-FCH significantly upregulated adenosine monophosphate-activated protein kinase phosphorylation and glucose transporter-2 expression, inhibited phosphoenolpyruvate carboxylase kinase activity, and elevated glycogen content in liver tissue of diabetic rats. Furthermore, P-FCH increased glucose consumption independently in normal and insulin-resistant HepG2 cells without the presence of insulin. The peptide composition of P-FCH was characterized. The potential biopeptides in P-FCH showed the sequence characteristic of a Val at the N-terminal or a Pro at the P2 position, and the hypoglycemic activity of Val-Pro-Leu-Gly (the most potential biopeptide in P-FCH) was verified by oral glucose tolerance test in mice. These results suggested that activation of the non-insulin-mediated AMPK pathway might be the determinant mechanism of P-FCH on the hypoglycemic effect. The novel peptide Val-Pro-Leu-Gly in P-FCH was effective in reducing blood glucose levels when orally administered to mice. © 2023 Society of Chemical Industry.

TMT-based quantitative proteomics analysis of Sprague-Dawley rats liver reveals Triphenyltin induced liver damage and lipid metabolism disorders

Triphenyltin (TPT) is a widely used pesticide that has a negative impact on biological health and production efficiency. In addition, TPT poses a threat to human health through the food chain and environmental pollution. However, the exact mechanism of TPT toxicity remains unclear. In this study, we investigated the hepatotoxicity of TPT and its effects on lipid metabolism using male SD rats as an animal model. Our results from HE and serum biochemical analysis suggested that TPT could damage liver structure and function, resulting in disruption of lipid metabolism. We therefore proceeded to analyze the proteomic response of rat liver tissue after 28 days of treatment with 2 mg/kg/d TPT. Our study demonstrates that TPT has a variety of effects on liver protein expression in rats. Through bioinformatic analysis, we observed significant changes in proteins related to fatty acid oxidation and synthesis due to TPT exposure. Furthermore, western blot and RT-qPCR experiments confirmed that TPT can affect lipid metabolism through the PPAR pathway. These findings suggest that TPT exposure can lead to liver damage, lipid accumulation and metabolic disorders.