Rat Liver Morphology Research Articles

Features of liver structural organization in posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a severe psychological condition resulting from traumatic experiences, leading to long-term physiological changes in the body. It affects mental health and induces hormonal imbalances that disrupt the hypothalamus-pituitary-adrenal axis, influencing multiple organ systems. While PTSD is often linked with comorbid conditions like depression and anxiety, its effects on the hepatobiliary system are less understood. Aim. This study aimed to assess PTSD's impact on liver morphology in rats of different sexes and compare the severity of changes between males and females, contributing to the understanding of stress-related physiological effects. Materials and Methods. The experiment involved 40 Wistar rats, divided into control and PTSD-induced groups for both sexes. A validated stress induction protocol was used, followed by a thorough morphological analysis of liver specimens fixed in 10% formalin and stained with hematoxylin-eosin. Histopathological evaluation focused on liver architecture, hepatocyte condition, vascular integrity, and cellular organization. Results. Control animals displayed standard liver structure, while PTSD-induced groups exhibited significant morphological changes, such as dystrophic alterations in hepatocytes, congestion in hepatic veins, and the formation of blood clots. Female rats showed more pronounced changes than males, including hepatocyte swelling and vacuolization, indicating heightened cellular stress and reduced regenerative capacity. Conclusions. The findings highlight that PTSD-related liver changes were more significant in female rats, emphasizing the importance of considering gender differences in stress-related disorders. These alterations suggest a complex interaction between chronic psychological stress and liver physiology, warranting further research on mechanisms by which PTSD affects the hepatobiliary system and potential therapeutic interventions. for at-risk populations.

Exploring the hepatoprotective potential of the probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide-postbiotic on ibuprofen-induced acute liver injury in rats.

The present study investigates the hepatoprotective effect of a probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide (EPS) against ibuprofen-induced acute liver injury, and to explore the involved underlying mechanisms. Hepatotoxicity was induced by administration of a single dose of ibuprofen (200 mg/kg body weight). The Lpb. plantarum E1K2R2 (109 CFU) and its EPS (200 mg/kg bw) were separately used to feed rats for seven consecutive days before ibuprofen administration. Liver toxicity was assessed by monitoring levels of serum liver enzymes, liver relative weight, oxidative stress and inflammatory markers, and through histopathological analysis. The results showed that ibuprofen administration significantly increased (P < 0.05) liver relative weight, elevated levels of alanine-amino transferase (ALT), aspartate-amino transferase (AST), decreased hepatic gluthatione (GSH) and endogenous antioxidant enzymes including, superoxide dismutase (SOD), catalase (CAT) and increased malondialdehyde (MDA) levels, nitric oxide (NO) and myeloperoxidase (MPO) in hepatic tissues. However, pre-treatment with Lpb. plantarum E1K2R2 and its EPS significantly attenuated these toxicity manifestations. Both pre-treatments restored liver weight, normalized transaminase enzyme levels, enhanced the activity of liver antioxidant enzymes (SOD and CAT), increased GSH content, and significantly reduced NO, MPO and MDA levels (P < 0.05), indicating their protective role against oxidative stress and inflammatory response induced by ibuprofen. Furthermore, histopathological analysis confirmed regular liver morphology in rats pre-treated with the probiotic and its EPS. These findings highlight the potential effectiveness of the probiotic Lpb. plantarum E1K2R2 and its EPS in mitigating ibuprofen-induced liver toxicity.

Safety analysis of different ıntensities of elf-pemf in terms of apoptotic, inflammatory, and transcription factor NF-Κb expression levels in rat liver.

The purpose of this research was to ascertain how exposure to extremely low-frequency pulsed electromagnetic fields (ELF-PEMFs) at varying intensities affects apoptosis-related protein expression levels and liver morphology in rats. In this experimental study, 40 Wistar albino rats were randomly divided into 4 groups, with 10 animals in each group: Control, Sham, 1 milli Tesla (1mT), and 5 mT groups. The control group did not expose any application during the experiment. Animals in the sham group were placed into the closed ELF-PEMF exposure environment, but the device was kept closed. The rats in the 1mT and 5mT groups were placed into a closed ELF-PEMF exposure environment, and the magnetic field application was applied 5 days a week for 4 hours a day for 8 weeks. At the end of the study, the animals were sacrificed, and their liver tissues were examined morphologically, and the expression levels of proteins related to apoptosis and inflammation in these tissues were analyzed. Our results indicated that ELF-PEMFs did not lead to any exact morphological alterations in the groups. Tissue apoptotic Bax and Caspase 3 expression levels in the 1mT and 5mT groups were similar (p>0.05) to the control group. Additionally, pro-inflammatory TNF-α and transcription factor NF-κB in the 1mT and 5mT groups were similar (p>0.05) to each other and the control group. It is feasible to conclude that neither the administration nor the exposure design of this study is changing the immunoexpression of apoptosis-regulating protein expression levels or liver morphology exposed to ELF-PEMF in rats.

Difference of lipid-lowering efficacy of "Xinjianqu" before and after fermentation and its mechanism based on LKB1-AMPK pathway and 16S rDNA sequencing technology

On the basis of establishing the prescription of Xinjianqu and clarifying the increase of the lipid-lowering active ingredients of Xinjianqu by fermentation, this paper further compared the differences in the lipid-lowering effects of Xinjianqu before and after fermentation, and studied the mechanism of Xinjianqu in the treatment of hyperlipidemia. Seventy SD rats were randomly divided into seven groups, including normal group, model group, positive drug simvastatin group(0.02 g·kg~(-1)), and low-dose and high-dose Xinjianqu groups before and after fermentation(1.6 g·kg~(-1) and 8 g·kg~(-1)), with ten rats in each group. Rats in each group were given high-fat diet continuously for six weeks to establish the model of hyperlipidemia(HLP). After successful modeling, the rats were given high-fat diet and gavaged by the corresponding drugs for six weeks, once a day, to compare the effects of Xinjianqu on the body mass, liver coefficient, and small intestine propulsion rate of rats with HLP before and after fermentation. The effects of Xinjianqu before and after fermentation on total cholesterol(TC), triacylglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), creatinine(Cr), motilin(MTL), gastrin(GAS), and the Na~+-K~+-ATPase levels were determined by enzyme-linked immunosorbent assay(ELISA). The effects of Xinjianqu on liver morphology of rats with HLP were investigated by hematoxylin-eosin(HE) staining and oil red O fat staining. The effects of Xinjianqu on the protein expression of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK), liver kinase B1(LKB1), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase(HMGCR) in liver tissues were investigated by immunohistochemistry. The effects of Xinjianqu on the regulation of intestinal flora structure of rats with HLP were studied based on 16S rDNA high-throughput sequencing technology. The results showed that compared with those in the normal group, rats in the model group had significantly higher body mass and liver coefficient(P&lt;0.01), significantly lower small intestine propulsion rate(P&lt;0.01), significantly higher serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2(P&lt;0.01), and significantly lower serum levels of HDL-C, MTL, GAS, Na~+-K~+-ATP levels(P&lt;0.01). The protein expression of AMPK, p-AMPK, and LKB1 in the livers of rats in the model group was significantly decreased(P&lt;0.01), and that of HMGCR was significantly increased(P&lt;0.01). In addition, the observed＿otus, Shannon, and Chao1 indices were significantly decreased(P&lt;0.05 or P&lt;0.01) in rat fecal flora in the model group. Besides, in the model group, the relative abundance of Firmicutes was reduced, while that of Verrucomicrobia and Proteobacteria was increased, and the relative abundance of beneficial genera such as Ligilactobacillus and Lachnospiraceae＿NK4A136＿group was reduced. Compared with the model group, all Xinjianqu groups regulated the body mass, liver coefficient, and small intestine index of rats with HLP(P&lt;0.05 or P&lt;0.01), reduced the serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2, increased the serum levels of HDL-C, MTL, GAS, and Na~+-K~+-ATP, improved the liver morphology, and increased the protein expression gray value of AMPK, p-AMPK, and LKB1 in the liver of rats with HLP and decreased that of LKB1. Xinjianqu groups could regulate the intestinal flora structure of rats with HLP, increased observed＿otus, Shannon, Chao1 indices, and increased the relative abundance of Firmicutes, Ligilactobacillus(genus), Lachnospiraceae＿NK4A136＿group(genus). Besides, the high-dose Xinjianqu-fermented group had significant effects on body mass, liver coefficient, small intestine propulsion rate, and serum index levels of rats with HLP(P&lt;0.01), and the effects were better than those of Xinjianqu groups before fermentation. The above results show that Xinjianqu can improve the blood lipid level, liver and kidney function, and gastrointestinal motility of rats with HLP, and the improvement effect of Xinjianqu on hyperlipidemia is significantly enhanced by fermentation. The mechanism may be related to AMPK, p-AMPK, LKB1, and HMGCR protein in the LKB1-AMPK pathway and the regulation of intestinal flora structure.

Systemic Biomarkers and Liver Morphology in Rats during Chronic Low-Dose Toxicant Administration against the Background of Vitamin Deficiency.

Liver morphology, intensity of apoptosis, and activity of xenobiotic metabolism enzymes were studied in a chronic model experiment in rats receiving a mixture of 6 pesticides against the background of life-long diets with adequate and insufficient supply of water-soluble vitamins. The dose of each pesticide in the mixture did not exceed the acceptable daily intake (1 ADI). It was found that chronic exposure to low doses of anthropogenic toxicants in combination with permanent vitamin deficiency provokes a number of liver changes, such as increased apoptosis activity, cytochrome P450 system depletion, steatosis, and inflammatory infiltration, which is a potential health risk factor.

Preventive Effect of Limosilactobacillus fermentum SCHY34 on Lead Acetate-Induced Neurological Damage in SD Rats

Lead poisoning caused by lead pollution seriously affects people's health. Lactic acid bacteria has been shown to be useful for biological scavenging of lead. In this experiment, Sprague-Dawley (SD) rats were treated with 200 mg/L of lead acetate solution daily to induce chronic lead poisoning, and oral Limosilactobacillus fermentum (L. fermentum) SCHY34 to study its mitigation effects and mechanisms on rat neurotoxicity. The L. fermentum SCHY34 showed competent results on in vitro survival rate and the lead ion adsorption rate. Animal experiments showed that L. fermentum SCHY34 maintained the morphology of rat liver, kidney, and hippocampi, reduced the accumulation of lead in the blood, liver, kidney, and brain tissue. Further, L. fermentum SCHY34 alleviated the lead-induced decline in spatial memory and response capacity of SD rats, and also regulated the secretion of neurotransmitters and related enzyme activities in the brain tissue of rats, such as glutamate (Glu), monoamine oxidase (MAO), acetylcholinesterase (AchE), cyclic adenosine monophosphate (cAMP), and adenylate cyclase (AC). In addition, the expression of genes related to cognitive capacity, antioxidation, and anti-apoptotic in rat brain tissues were increased L. fermentum SCHY34 treatment, such as brain-derived neurotrophic factor (BDNF), c-fos, c-jun, superoxide dismutase (SOD)1/2, Nuclear factor erythroid 2-related factor 2 (Nrf2), and B-cell lymphoma 2 (Bcl-2), and so on. L. fermentum SCHY34 showed a great biological scavenging and potential effect on alleviating the toxicity of lead ions.

Effect of Polysaccharide-Based Film on Morphometric Parameters of Rat liver

In the modern world, most manufacturers try to use film coatings that have the following properties: manufacturability, safety, biodegradability, and economic availability. The provided materials present the results of studying the effect of a film based on polysaccharides on the morphology of rat liver. An experiment was carried out on laboratory animals, in the course of its carrying out the morphological structure of the rat liver was studied, which showed that use of films based on polysaccharides is safe for laboratory animals.

Effect of Silicon Dioxide Nanoparticles on Liver Morphology of Rats in Parenteral Administration

The issue of the potential safety of silicon dioxide nanoparticles (SDNPs) remains relevant. In this connection, in order to use the unique capabilities of silicon nanostructures for biomedical purposes, as well as to level their toxic effects, a detailed study of these nanoparticles interaction with cells and tissues in vivo is required.The aim of the research is to reveal morphofunctional changes in a rat's liver after a single parenteral administration of 12 nm silicon dioxide nanoparticles for the period of six months.Material and methods. Using general histological and immunohistochemical methods to study the rats' liver after a single parenteral administration of 1 ml of silicon dioxide nanoparticles at a dose of 7 mg/kg of body weight at a concentration of 2 mg/ml. The sections of the rats' liver were studied by general histological and immunohistochemical methods after injection of 1mL of a SDNPs saline suspension at a concentration of 2 mg/mL (7mg/kg of body weight). Control animals were injected with 1 ml of saline solution. The material was collected in 21 days, 2, 4 and 6 months months after the administration of the SDNPs and it was fixed in 10% neutral formaldehyde.Results. The formation of granulomas in the liver on the 21st day of the experiment and an increase in the number of Kupfer cells were revealed. However, by the 2nd month of the experiment, the number of granulomas significantly decreases compared to the 21st day of the experiment and continues to decrease in subsequent periods. The average size of granulomas decreases during the 2nd month of the experiment and does not change during the subsequent periods of the experiment. After 6 months of the experiment, the morphofunctional state of the liver is characterized by slightly pronounced aseptic inflammation.Conclusion. A single parenteral administration of silicon dioxide nanoparticles causes pronounced aseptic inflammation of the liver, decreasing by the 6th month of the experiment. Connective tissue remodeling in the liver is not observed at all periods of the experiment.

Effects of prolonged subchronic benzo(α)pyrene exposure on rat liver morphology and CYP1A expression during treatment with menadione, quercetin, or tocopherol

Arylamines and polycyclic aromatic hydrocarbons (PAHs) are hazardous anthropogenic pollutants in the environment. The toxicity of PAHs, which include benzo(α)pyrene (BP), is mediated by the activation of Р450 cytochromes of the 1А subfamily (CYP1A1 and CYP1A2). Previously, we have demonstrated that tocopherol, quercetin, and menadione inhibit the expression and activity of CYP1A in the liver of male Wistar rats after administration of a high BP dose to the rats for 3 days. Here, we confirmed the effects of tocopherol, quercetin, and menadione on the expression and activity of CYP1A and on rat liver morphology during prolonged administration (90 days) of a low BP dose. We revealed that subchronic oral administration of a low BP dose has no influence on CYP1A expression as compared to controls but can cause pathomorphological changes in rat liver tissue. These changes are abrogated by tocopherol, attenuated by quercetin, and enhanced by menadione.

The incretin enhancer, sitagliptin, exacerbates expression of hepatic inflammatory markers in rats fed a high-cholesterol diet

Hypercholesterolemia is associated with the development of a pro-inflammatory state and is a documented risk factor for progression to insulin resistance, nonalcoholic fatty liver and cardiovascular diseases. Sitagliptin is an incretin enhancer that improves glucose tolerance by inhibiting dipeptidyl peptidase-4, but it also has reported anti-inflammatory effects. The current study was thus undertaken to examine the interactions of dietary Cholesterol (Cho)and sitagliptin on markers of inflammation. Male Sprague-Dawley rats were provided diets high in Cho and gavaged with vehicle or an aqueous suspension of sitagliptin (100mg/kg/day) from day 10 through day 35. Molecular methods were used to analyze the lipid profile and inflammatory markers in liver and serum samples. H&E-stained liver sections were used for histopathological evaluation. Hepatic influx of mononuclear cells and necrosis were assessed by immunohistochemistry. Sitagliptin reduced triglyceride andCho levels in serum of rats on the control diet but these effects were abrogated in rats on the high-Cho diet. Sitagliptin produced a significant increase in the expression of hepatic inflammatory markers (Tnfa, Il1b, and Mcp1) and a corresponding increase in serum TNFα and IL-1β in rats on the high-Cho diet, but it had no effect on rats on the control diet. Additionally, sitagliptin had no effect on liver morphology in rats on the control diet, but it produced hepatic histopathological changes indicative of necrosis and mononuclear cell infiltration in rats on the high-Cho diet. These mononuclear cells were identified as macrophages and T cells. When provided in the context of a high-Cho diet, these findings reveal previously unrecognized hepato-inflammatory effects of sitagliptin that are accompanied by evidence of hepatic necrosis and mononuclear cell infiltration.

The cytotoxic properties of zinc oxide nanoparticles on the rat liver and spleen, and its anticancer impacts on human liver cancer cell lines.

Due to their unique properties including cellular uptake and the delivery efficiency to biological systems, nanoparticles are used in various preclinical and clinical applications. The aim of this study was to investigate the toxicity impacts of zinc oxide nanoparticles (ZnO-NPs) on morphology and functionality of the rat's liver and spleen and illustrated its safe-therapeutic doses. The 28 female Swiss albino rats (180-220 g) and two human hepatocyte cell lines (HepG2 and HUH7) were designed as an in vivo and in vitro study, respectively. Samples were treated with certain doses of ZnO-NPs. The rat's liver morphology and functionality and apoptotic genes expression profile (Bax, Bcl-2, and P53) were analyzed to detect the cytotoxicity and antitumor impacts of ZnO-NPs, respectively. The results showed a positive significant association between the increasing doses of ZnO-NPs and alanine aminotransferase/aspartate aminotransferase values. Moreover, a meaningful correlation was detected between the rat's liver and spleen weight and ZnO-NPs doses. Furthermore, the histopathological analysis of rat's liver showed the individual cytotoxic properties of ZnO-NPs. Finally, the positive significant correlation was detected among the expression of Bax and P53 genes with ZnO-NPs. In addition, the negative correlation was demonstrated between the expression of Bcl-2 and ZnO-NPs. In general, in the current study, the antitumor effects of ZnO-NPs were confirmed by the enhancement of P53 and Bax genes expression profile, which are indicated the apoptotic induction in HUH7 cell line. Moreover, we introduced a safe-clinical ZnO-NPs dosage, have antitumor effects.

Effect of long-term immunosuppressive therapy on native rat liver morphology and hepatocyte- apoptosis

A negative result of therapy based on immunosuppressive drugs is its leading to pathological alterations in the organ, including liver. Use of immunosuppressive medication may also lead to organized and genetically controlled cell death – apoptosis. The aim of this study was to examine histopathological changes in the livers of rats treated with immunosuppressive drugs, and also to determine the effects of different groups of immunosuppressive drugs on apoptosis activity in the hepatocytes of rat livers. The study was conducted on archival material obtained from Department of Nephrology, Transplantology and Internal Medicine of the Independent Public Clinical Hospital No. 2 at the Pomeranian Medical University in Szczecin, Poland.Statistical comparison of the treatment groups showed that all groups with rapamycin (sirolimus)-based regimens: Tacrolimus, Rapamycin, Glucocorticosteroid (TRG); Cyclosporine, Rapamycin, Glucocorticosteroid (CRG); Mycophenolate, Rapamycin, Glucocorticosteroid (MRG) and additionally Cyclosporine, Mycophenolate, Glucocorticosteroid (CMG) exhibited significantly more pronounced apoptosis than the control group, with p < 0.01, p < 0.05, p < 0.01 and p < 0.01, respectively. Furthermore, in the TRG group, over 90% of apoptotic hepatocytes were seen in the examined classic lobules. Additionally, every liver from treatment group was pathologically altered, including dilated sinusoids, pyknotic nuclei, swollen walls of the vessels.Long-lasting immunosuppressive treatment affects the liver both in terms of histological changes within the structure of the liver and in terms of the percentage of apoptotic hepatocytes.The following study seems to be very innovating due to the duration of the experiment and used drugs-protocols, since they reflect human treatment.

Pathological and immunohistochemical effects of electromagnetic fields on rat liver

The aim of this study was to investigate the possible effects of 50 Hz electromagnetic fields (EMFs) generated by high power lines on the morphology of rat liver and apoptosis. For this purpose, 28 adult male rats weighing 200-250 g were used. The treatment groups were kept in a shelter that were 7.5 m far from the high power lines carrying 170 kV (50 Hz) energy. The control animals (Group 1) were kept in an animal house where no electromagnetic fields were exposed. The animals of the groups 2, 3 and 4 were exposed to EMF (170 kV, 50 Hz) continously for 1, 2 and 3 months, respectively. At the end of the study periods, the animals were sacrificed and their livers were collected. Histopathological evaluation indicated that inflammatory cell infiltration localized in the portal areas was seen in the liver of experimental groups rats. Bax and Bcl-2 positive staining was observed in the liver of control and experimental groups, but both Bax and Bcl-2 staining was intense in Group 3. In conclusion, long- term exposure to EMFs may cause inflammatory changes and apoptosis in liver of rats.

Importance Rat Liver Morphology and Vasculature in Surgical Research.

BackgroundThe laboratory rat is one of the most popular experimental models for the experimental surgery of the liver. The objective of this study was to investigate the morphometric parameters, physiological data, differences in configuration of liver lobes, biliary system, and vasculature (arteries, veins, and lymphatic vessels) of the liver in laboratory rats. In addition, this study supports the anatomic literature and identified similarities and differences with human and other mammals.Material/MethodsForty laboratory rats were dissected to prepare corrosion casts of vascular system specimens (n=20), determine the lymph vessels and lymph nodes (n=10), and for macroscopic anatomical dissection (n=10) of the rat liver. The results are listed in percentages. The anatomical nomenclature of the liver morphology, its arteries, veins, lymph nodes, and lymphatic vessels are in accordance with Nomina Anatomica Veterinaria.ResultsWe found many variations in origin, direction, and division of the arterial, venous, and lymphatic systems in rat livers, and found differences in morphometric parameters compared to results reported by other authors. The portal vein was formed by 4 tributaries in 23%, by 3 branches in 64%, and by 2 tributaries in 13%. The liver lymph was drained to the 2 different lymph nodes. The nomenclature and morphological characteristics of the rat liver vary among authors.ConclusionsOur results may be useful for the planing of experimental surgery and for cooperation with other investigation methods to help fight liver diseases in human populations.

The effect of alkaloids present in blue lupine (Lupinus angustifolius) seeds on the growth rate, selected biochemical blood indicators and histopathological changes in the liver of rats

The objective of this study was to determine the effect of alkaloids present in blue lupine (Lupinus angustifolius) seeds on the growth rate, selected indicators of carbohydrate and lipid metabolism, and liver morphology in rats. The experimental material comprised 32 Wistar rats at around 3 weeks of age, with an initial body weight of 81 g. During a 28-day feeding trial, the rats were fed diets containing the seeds of three blue lupine cultivars, Baron, Zeus and Wersal, with different alkaloid concentrations (0.36, 0.41, 0.56 mg/kg, respectively). Diets containing the seeds of three blue lupine cultivars reduced the feed intake and significantly limited the growth rate of experimental rats, compared to the control group. Lupine alkaloids had no effect on the serum concentrations of glucose and total cholesterol in rats, whereas elevated triglyceride concentrations were noted in experimental groups, relative to the control group. Diets containing the seeds of blue lupine cultivars Zeus and Wersal induced changes in alanine transaminase activity. A histopathological analysis of the liver revealed parenchymatous degeneration, which was more advanced in rats fed diets with the seeds of blue lupine cultivars Zeus and Wersal than in the control group, and congestion of portal vessels, which was more severe in rats fed the seeds of blue lupine cultivars Baron and Zeus.

Effects of raftilose on serum biochemistry and liver morphology in rats fed with normal or high‐fat diet

Non-alcoholic fatty liver disease is the leading cause of chronic liver injury in developed countries. Oligofructose (OFS) is a prebiotic with proven benefits for health. The aim of the study is to evaluate the effect of 10% OFS on hepatic morphology and lipid metabolism in Wistar Kyoto rats submitted to normal diet (ND) or high-fat diet (FD). Animals were treated for 7 weeks. Lipid profile and serum alkaline phosphatase (ALP) activity were measured and liver histology evaluated at the end of the study. Ten percent OFS reduced triglyceride (TAG) levels when added to any of the diet regimens; 10% OFS decreased plasmatic urea in ND and plasmatic and urinary urea levels in FD; ND + 10% OFS treated rats showed lower ALP activity than controls. FD increased ALP activity, an effect not reversed by OFS. Animals submitted to FD have microscopic hepatic changes: marked steatosis with disarranged centrilobular zone structure; enlarged sinusoids; enlarged mitochondria and an increase in number and volume of adiposomes. Supplementation with 10% OFS in FD reversed those effects. In conclusion, 10% OFS supplementation prevented deleterious effects of FD such as alterations on lipid profile (TAG elevation) and hepatic morphologic changes. OFS decreased ALP activity in animals subjected to ND, which may have contributed to the differences on lipid metabolism.

Influence of methyl and isopropyl N-methyl antranilates on carbon tetrachloride-induced changes in rat liver morphology and function

The aim of the present study was to examine potential protective effects of methyl N-methylanthranilate (M) and isopropyl N-methylanthranilate (I) in a rat model of acute intoxication with carbon tetrachloride (CCl4) by tracking the changes in liver morphology and function. Serum transaminase and bilirubin were significantly elevated in animals treated with CCl4 alone. A pretreatment with M and I prior to the administration of CCl4 significantly prevented the increase of serum levels of liver damage markers. Histopathological evaluation of the livers of the test animals also revealed that M and I reduced the incidence of liver lesions. Our experiments showed that both M and I possess protective effect in CCl4-induced liver damage in rats. The results are of interest due to the presence of natural or synthetic M in the human diet.

Anti-inflammatory effect of natural heterocycle glucoside vicine obtained from Vicia faba L. its aglucone (divicine) their effect on some oxidative stress biomarkers in Albino rats

ABSTRACT Background: Inflammation is typically characterized by increased permeability of endothelial tissue resulting in oedema. Much of pyrimidine derivatives have been highly useful for treating acute and self-limited inflammatory conditions. This study was performed to explore the acute toxicity, anti-inflammatory activity and biochemical effect of natural heterocycle pyrimidine glucoside vicine obtained from Vicia faba L. and its aglucone (divicine) and their effect on some oxidative stress biomarkers in Albino rats. Also, the anti-inflammatory effect of the tested compounds were compared with diclofenac sodium (100 mg/kg bw). On the other hand, this article was extended to assess the impact of a very high dose of diclofenac sodium (100 mg/kg bw) on liver enzymes, which was used by many authors to explain the negative effects of diclofenac when used at this dose as a standard anti-inflammatory drug. Methods: The median lethal dose (LD 50 ) and histopathological effects of vicine and divicine was determined in order to assess their safety. Also, the inflammatory effect of the tested compounds was examined at doses (50–200 mg/kg bw) in rats, using fresh egg albumin-induced oedema and compared with standard anti-inflammatory drugs, diclofenac sodium (100 mg/kg bw). Finally, vicine and divicine treatment (50—200 mg/kg bw) was evaluated for 10 consecutive days prior in Albino rats in the serum levels of hepatic enzymes, glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), gamma glutamyl transferase (γ-GT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), super oxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARs). Results: Vicine and divicine were found to have an LD 50 of 2100 and 1950 mg/ kg bw orally, respectively and a significant (p vicine and divicine, respectively, at 150 mg/kg against the fresh egg albumin-induced oedema in rats after 180 min. Also, the standard anti-inflammatory diclofenac sodium (100 mg/kg) showed 100% inhibition against the fresh egg albumin-induced oedema in rats after 180 minutes. In addition, administration of vicine and divicine orally to the rats at doses of 50—200 mg/kg bw for 10 days showed non-significant changes in liver enzymes and serum TBARs as compared with the control group. But administration of diclofenac sodium orally at a concentration of 100 mg/kg bw daily for 10 consecutive days to rats showed significant increase in liver enzymes and serum TBARs and significant decrease in blood GSH, SOD and GPx. Histopathology of the rat liver morphology of all the treated groups showed no disorder except for the photomicrograph of the cross section of liver from rats treated with diclofenac sodium 100 mg/kg for 10 consecutive days, shows pronounced dilatation of the hepatic portal vein. Conclusion: The observation allows conclusion that vicine and divicine at concentration of 50—150 mg/kg bw exhibited good anti-inflammatory effect and have no hepatotoxic activity.

Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with Nω-nitro-L-arginine methyl ester (L-NAME)

Chronic treatment of rats with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension mediated partly by enhanced angiotensin-I-converting enzyme (ACE) activity. We examined the influence of L-NAME on rat liver morphology, on hepatic glycogen, cholesterol, and triglyceride content, and on the activities of the cytochrome P450 isoforms CYP1A1/2, CYP2B1/2, CYP2C11, and CYP2E1. Male Wistar rats were treated with L-NAME (20 mg/rat per day via drinking water) for 2, 4, and 8 weeks, and their livers were then removed for analysis. Enzymatic induction was produced by treating rats with phenobarbital (to induce CYP2B1/2), beta-naphthoflavone (to induce CYP1A1/2), or pyrazole (to induce CYP2E1). L-NAME significantly elevated blood pressure; this was reversed by concomitant treatment with enalapril (ACE inhibitor) or losartan (angiotensin II AT(1) receptor antagonist). L-NAME caused vascular hypertrophy in hepatic arteries, with perivascular and interstitial fibrosis involving collagen deposition. Hepatic glycogen content also significantly increased. L-NAME did not affect fasting glucose levels but significantly reduced insulin levels and increased the insulin sensitivity of rats, based on an intraperitoneal glucose tolerance test. Immunoblotting experiments indicated enhanced phosphorylation of protein kinase B and of glycogen synthase kinase 3. All these changes were reversed by concomitant treatment with enalapril or losartan. L-NAME had no effect on hepatic cholesterol or triglyceride content or on the basal or drug-induced activities and protein expression of the cytochrome P450 isoforms. Thus, the chronic inhibition of NO biosynthesis produced hepatic morphological alterations and changes in glycogen metabolism mediated by the renin-angiotensin system. The increase in hepatic glycogen content probably resulted from enhanced glycogen synthase activity following the inhibition of glycogen synthase kinase 3 by phosphorylation.

A light- and electron-microscope study of hepatocytes of rats fed different diets

Ketogenic diets are used in the treatment of epilepsy in children refractory to drug therapy. This study identifies changes in liver morphology in rats fed four different diets: a normal rodent chow diet, a calorie-restricted high-fat (ketogenic) diet and each diet supplemented with clofibric acid. Hepatocytes of rats fed the ketogenic diet show many lipid droplets and these are reduced to control levels when clofibrate is present in the diet. Mitochondria are enlarged in the livers of rats fed the ketogenic diet and further enlarged if clofibrate is present. Alterations in the appearance or numbers of other organelles are also found. To cite this article: D.A. Eagles, G.B. Chapman, C. R. Biologies 330 (2007).