Histopathological Examination Of Liver Tissues Research Articles

The hepatoprotective effect of 4-phenyltetrahydroquinolines on carbon tetrachloride induced hepatotoxicity in rats through autophagy inhibition

BackgroundThe liver serves as a metabolic hub within the human body, playing a crucial role in various essential functions, such as detoxification, nutrient metabolism, and hormone regulation. Therefore, protecting the liver against endogenous and exogenous insults has become a primary focus in medical research. Consequently, the potential hepatoprotective properties of multiple 4-phenyltetrahydroquinolines inspired us to thoroughly study the influence of four specially designed and synthesized derivatives on carbon tetrachloride (CCl4)-induced liver injury in rats.Methods and resultsSeventy-seven Wistar albino male rats weighing 140 ± 18 g were divided into eleven groups to investigate both the toxicity profile and the hepatoprotective potential of 4-phenyltetrahydroquinolines. An in-vivo hepatotoxicity model was conducted using CCl4 (1 ml/kg body weight, a 1:1 v/v mixture with corn oil, i.p.) every 72 h for 14 days. The concurrent treatment of rats with our newly synthesized compounds (each at a dose of 25 mg/kg body weight, suspended in 0.5% CMC, p.o.) every 24 h effectively lowered transaminases, preserved liver tissue integrity, and mitigated oxidative stress and inflammation. Moreover, the histopathological examination of liver tissues revealed a significant reduction in liver fibrosis, which was further supported by the immunohistochemical analysis of α-SMA. Additionally, the expression of the apoptotic genes BAX and BCL2 was monitored using real-time PCR, which showed a significant decrease in liver apoptosis. Further investigations unveiled the ability of the compounds to significantly decrease the expression of autophagy-related proteins, Beclin-1 and LC3B, consequently inhibiting autophagy. Finally, our computer-assisted simulation dockingonfirmed the obtained experimental activities.ConclusionOur findings suggest that derivatives of 4-phenyltetrahydroquinoline demonstrate hepatoprotective properties in CCl4-induced liver damage and fibrosis in rats. The potential mechanism of action may be due to the inhibition of autophagy in liver cells.

Nicorandil/ morphine crosstalk accounts for antinociception and hepatoprotection in hepatic fibrosis in rats: Distinct roles of opioid/cGMP and NO/KATP pathways

Previous report indicated that nicorandil potentiated morphine antinociception and attenuated hepatic injury in liver fibrotic rats. Herein, the underlying mechanisms of nicorandil/morphine interaction were investigated using pharmacological, biochemical, histopathological, and molecular docking studies. Male Wistar rats were injected intraperitoneally (i.p.) with carbon tetrachloride (CCl4, 40%, 2 ml/kg) twice weekly for 5 weeks to induce hepatic fibrosis. Nicorandil (15 mg/kg/day) was administered per os (p.o.) for 14 days in presence of the blockers; glibenclamide (KATP channel blocker, 5 mg/kg, p.o.), L-NG-nitro-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor, 15 mg/kg, p.o.), methylene blue (MB, guanylyl cyclase inhibitor, 2 mg/kg, i.p.) and naltrexone (opioid antagonist, 20 mg/kg, i.p.). At the end of the 5th week, analgesia was evaluated using tail flick and formalin tests along with biochemical determinations of liver function tests, oxidative stress markers and histopathological examination of liver tissues. Naltrexone and MB inhibited the antinociceptive activity of the combination. Furthermore, combined nicorandil/morphine regimen attenuated the release of endogenous peptides. Docking studies revealed a possible interaction of nicorandil on µ, κ and δ opioid receptors. Nicorandil/morphine combination protected against liver damage as evident by decreased liver enzymes, liver index, hyaluronic acid, lipid peroxidation, fibrotic insults, and increased superoxide dismutase activity. Nicorandil/morphine hepatoprotection and antioxidant activity were inhibited by glibenclamide and L-NAME but not by naltrexone or MB. These findings implicate opioid activation/cGMP versus NO/KATP channels in the augmented antinociception, and hepatoprotection, respectively, of the combined therapy and implicate provoked cross talk by nicorandil and morphine on opioid receptors and cGMP signaling pathway. That said, nicorandil/morphine combination provides a potential multitargeted therapy to alleviate pain and preserve liver function.

The effect of krill oil on Wnt/β-catenin signaling pathway in acetaminophen-induced acute liver injury in mice

Abstract Objectives This study investigated the effect of krill oil (KO) on liver damage caused by acetaminophen (APAP). Methods In the present study, the control and APAP groups were given distilled water by gavage for 14 days. In addition, the KO and APAP+KO groups were given 500 mg/kg krill oil by gavage for 14 days. At the end of 14 days, 0.9 % sodium chloride solution (saline solution) administration was applied intraperitoneally to the control and KO groups. Meanwhile, 220 mg/kg acetaminophen was administered to the APAP and APAP+KO groups. While some biochemical parameters in plasma were examined, some oxidative stress parameters in plasma and liver tissue were evaluated. Apoptotic and inflammatory responses of some primer sequences determined by quantitative Real-Time PCR (qPCR) in liver tissue. After histopathological examination of liver tissue, immunohistochemical analysis was performed with Wnt inhibitory factor-1 (Wif-1), beta-catenin (β-Catenin), and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Results The Wif-1 positivity in hepatocytes increased significantly in the APAP group (5.29 ± 0.71) compared to the control (1.14 ± 0.51), and KO (2.14 ± 0.55) groups (p<0.001). The 8-OHdG positivity in hepatocytes increased significantly in the APAP group (19.57 ± 0.58) compared to the control (0.43 ± 0.20), KO (3.57 ± 0.48), and APAP+KO (4.00 ± 2.53) groups (p<0.001). Conclusions As a result, krill oil could be used as a nutritional supplement to protect the liver against acetaminophen-induced liver injury.

Susceptibility of selected tropical non-tilapine ornamental cichlids to Tilapia tilapinevirus following experimental infection

The emergence and spread of transboundary aquatic animal diseases have been frequently associated with international trade of live aquatic animals. Tilapia is one of the most traded aquatic animals and the recent global spread of Tilapia tilapinevirus, also known as tilapia lake virus (TiLV), is speculated to be due to transboundary movement of infected fish. Further, extensive trade of ornamental cichlids can be a major threat to the spread of TiLV. However, there is little information about susceptibility of ornamental fishes, especially cichlids, to this virus. In this background, the present study evaluated the susceptibility of three ornamental cichlids (angelfish, firemouth cichlid and parrotfish) and two non-cichlids (three spot gourami and goldfish) vis-à-vis Nile tilapia following experimental infection with TiLV through intraperitoneal injection. The study carried out quantification of viral load using real-time PCR, histopathology and isolation of the virus in permissive cell line developed previously from Oreochromis niloticus heart (OnH). Experimental infection resulted in the successful reproduction of the disease in tilapia with typical clinical signs. In angelfish, 40% mortality was observed and the TiLV copy number/100 ng RNA was determined to be 2.49 × 106, 1.52 × 106 and 2.64 × 104 in the target tissues, namely liver, spleen and brain, respectively at 4 days post-infection (dpi). In addition, TiLV could be detected in the target tissues till end of the experimental period of 24 days. Although no clinical signs or mortality were observed in firemouth cichlid, but TiLV copies were detected in the target organs with significant increase in the viral load up to 12 dpi. Histopathological examination of liver tissue of the experimentally infected fishes revealed typical syncytial cells only in tilapia whereas necrosis of hepatocytes was observed in tilapia, angelfish and firemouth cichlid. Besides, TiLV could be isolated from target tissues of both angelfish and firemouth cichlid at 8 dpi, using OnH cell line. On the other hand, in parrotfish, three spot gourami and goldfish, the virus copy number in the target tissues showed a decline from 1 dpi and no evidence of virus replication could be noticed in the cell line studies. Hence, these three ornamental fishes were considered resistant to experimental infection with TiLV. The findings of this study indicated the existence of wide host-range of TiLV in non-tilapine ornamental fishes including angelfish and firemouth cichlid, and the potential role of these fishes in the epidemiology of TiLV disease.

Asemptomatik ve semptomatik hastalarda karaciğer biyopsi sonuçlarına göre karaciğer transaminaz anormalliklerinin retrospektif olarak değerlendirilmesi

Background and Aim: Histopathological examination of liver tissue is often performed with percutaneous liver biopsy. In this study, we aimed to evaluate the causes and results of liver biopsy performed for various reasons in our clinic between years 2016 and 2019. Materials and Methods: 554 of 750 liver biopsies performed between July 2016 and January 2019 were included in the study. Pathology results of liver biopsies, the clinical information of the same patients were obtained from the patient files. Biopsy indications and results of the patients were evaluated retrospectively. Results: 554 liver biopsy results (M:323, 58.4%; mean age: 45±14.3) were included in the study. The most common liver biopsy indication in our hospital, was determined as the biopsies of patients with chronic hepatitis B. This indication was followed by liver biopsies performed to examine non-viral liver enzyme elevations.The pathology results were listed as; chronic hepatitis B (65%), NAFLD/NASH (16%), AIH (3%), Hepatitis C (3%) respectively. Discussion: The diversity in liver biopsy results shows the importance of histopathological evaluation. In order to reach healthy data, multi-centered prospective randomized controlled studies with larger populations are needed.

Immunomodulatory effect of Linalool (Lin) against CCl4 -induced hepatotoxicity and oxidative damage in rats.

The current study explored the hepatoprotective and immunomodulatory effects of Linalool (Lin) against carbon tetrachloride (CCl4 )-induced toxicity in mice. Four study groups (n = 8 each) were used: (1) a negative control group and (2) a toxicity control group (single dose of CCl4 administered on day 14 as 1 mL/kg of CCL4 in 1% olive oil). Intraperitoneally (i.p.)), and two experimental groups where mice were treated with either (3) Lin (25 mg/kg b.w., orally, daily for 15 days) or (4) pretreated with Lin (25 mg/kg b.w., orally, daily for 14 days) and intoxicated with CCl4 (1 mL/kg of CCL4 in 1% olive oil. i.p.) on day 14. The levels of the anti-inflammatory cytokine interleukin 10 (IL-10), the proinflammatory cytokines TNF-α, IL-6, and TGF-1β, and the histopathology of the liver were assessed. According to our findings, IL-10 concentrations were significantly increased in Lin-treated groups, while other cytokine levels were marked by a considerable decrease in the toxicity model group (CCl4 -treated group). Histopathological examinations of liver tissues showed that the Lin-treated groups had an almost normal structure. The current findings showed that Lin could inhibit CCl4 -induced liver injury in mice, which warrants further investigation of Lin as a potential protective and therapeutic agent against hepatotoxicity.

Clinicohematological, Mutagenic, and Oxidative Stress Induced by Pendimethalin in Freshwater Fish Bighead Carp (Hypophthalmichthys nobilis).

Currently, aquatic and terrestrial ecosystems are continuously and chronically polluted by cocktails of countless chemical compounds. The susceptibility to infections is tremendously increasing in a variety of organisms due to exposure to environmental pollutants. Pendimethalin, an herbicide, is continuously used in agriculture to remove unwanted broadleaf weeds across the globe. Therefore, this study investigates the mechanisms of toxicity of pendimethalin in freshwater fish bighead carp upon exposure to low and environmentally relevant concentrations. For this purpose, 48 fish without any clinical abnormalities were kept in a glass aquarium in different experimental groups (T0, T1, T2, and T3). These groups were treated with pendimethalin at 0.00, 0.25, 0.50, and 0.75 mg/L, respectively. Four fish were randomly picked from each experimental group and killed at 72, 96, and 120 hours of the trial to study hematobiochemical parameters and visceral tissues including the brain, liver, heart, gills, and kidneys for histopathology. Herbicide-treated fish indicated various physical and behavioral abnormalities including hypersecretion of mucus, erratic swimming, operculum movement, air gulping, tremors of fins, loss of equilibrium, and increased surface breathing. Histopathologically, gills tissues of treated fish indicated atrophied lamellae, uplifting of secondary lamellae, necrosis of primary and secondary lamellar epithelial cells, telogenesis, congestion, and lamellar fusion. Histopathological examination of liver tissues of treated fish showed mild to moderate congestion, necrosis of hepatocytes, and atrophy of hepatocytes while kidneys revealed degeneration of renal tubules, glomerular atrophy, ceroid, and necrosis of renal tubules. The erythrocyte counts, monocyte and lymphocyte counts, and hemoglobin values were significantly (P < 0.05) reduced in pendimethalin-treated fish. Results on serum biochemistry showed that the biomarkers of kidneys, heart, and liver were significantly higher in fish of treated groups. In addition, values of different biochemical reactions like reactive oxygen species (ROS), thiobarbituric acid reactive species (TBARS), total proteins, and quantity of different antioxidant enzymes including reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) were significantly different when compared to untreated fish. Moreover, the percentile of different nuclear abnormalities in red blood cells and frequency of DNA damage increased significantly in treated fish. It can be concluded from the findings that pendimethalin causes its toxic effects via disruption of physiological and hematobiochemical reactions of fish.

Efficacy of Melatonin and Pentoxifylline combination therapy in treatment of endotoxin induced hepatic dysfunction in white albino mice

Introduction:&#x0D; Despite major expansion and elaboration in treatment protocols of septic patients, mortality rate is still very high due to multiple organ damage including hepatotoxicity. We in study evaluated the role of two strong anti-inflammatory agents, melatonin and pentoxifylline, as a combined treatment in lipopolysaccharide induced hepatic dysfunction in white albino mice.&#x0D; Material and Methods:&#x0D; Endotoxemia was reproduced in white albino mice through intraperitoneal administration of lipopolysaccharide (LPS) of serotype E.Coli. Therapeutic potential of the both melatonin and pentoxifylline alone and as combined therapy was adjudged by administering agents 2 hours after LPS delivering. The extent of liver damage was evaluated via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with histopathological examination of liver tissue.&#x0D; Results: Lipopolysaccharide administration (Group 2) resulted in marked hepatotoxicity as evident by statistically raised serum ALT ((p≤0.01) and AST (p≤0.01) at the end of experimentation. Also liver cross section examination showed marked distortion of liver parenchyma. Melatonin (Group 3) was prosperous in aversion of LPS invoked hepatotoxicity as proved by lessening of augmented ALT (p≤0.01) and AST (p≤0.01) along with restoration of pathological changes on liver sections (p≤0.05). Pentoxifylline generated similar results and serum ALT, AST and histological alteration abated considerably (p≤ 0.05).Combination therapy in animals of Group 5 also tapered LPS evoked hepatic dysfunction statistically considerably.&#x0D; Conclusion: Melatonin and pentoxifylline alone and as combination therapy as effective in countering LPS induced hepatotoxicity. However the combination therapy did not yield synergistic effects.&#x0D; Keywords:&#x0D; Lipopolysaccharides, Endotoxin, Hepatotoxicity, Melatonin, Pentoxifylline.

Effect of an Extract from the Egyptian Sea Cucumber, Bohadschia marmorata, on Methotrexate-Induced Hepatorenal Toxicity in Male Mice.

Background:The sea cucumber, Bohadschia marmorata, is a marine echinoderm consumed and used as a medication. Extract of this species displays a broad spectrum of bioactivity, such as antifungal, antibacterial, immunomodulatory, and cytotoxic properties. This investigation explored sea cucumber extract for hepatorenal protection against the toxicity of methotrexate (MTX). Methods:Four groups of mice were divided into G1: control, G2: MTX treated, G3: B. marmorata extract-treated daily for 14 days, and G4: B. marmorata extract and MTX treated. Results and Conclusions:Biochemical analysis and histopathological examination of liver tissue showed that administration of MTX increased serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), lowered levels of serum albumin, total protein, Superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Administration of B. marmorata extract to MTX- injected mice significantly reversed the increase in serum levels of liver enzymes and induced a significant elevation in serum albumin and total protein levels. SOD, CAT, and GSH levels returned to nearly normal levels. Histopathological examination indicated fewer signs of toxicity in liver and kidney tissues of mice treated with both extract and MTX compared to MTX treatment alone. An extract of B. marmorata will protect mice from hepatorenal toxicity induced by MTX.

Downregulation of TLR4-NF-?B-p38 MAPK Signalling in Cholestatic Rats Treated with Cranberry Extract.

&lt;b&gt;Background and Objective:&lt;/b&gt; Cholestasis is a liver disease that occurs when bile flow is restricted or blocked. Estrogen-induced cholestasis is marked by a reduction in bile flow and the accumulation of bile acids in the liver as well as liver damage. The aim was to evaluate the hepatoprotective effect on EE-induced cholestasis in rats of Cranberry Water Extract (CWE). &lt;b&gt;Materials and Methods:&lt;/b&gt; Adult albino rats weighing approximately 150±10 g were divided into six groups of six animals each. As control groups, three groups (I, II and IV) and three experimental groups were used (III, V, VI). &lt;b&gt;Results:&lt;/b&gt; Oral administration for 15 days of CWE (150 mg kg&lt;sup&gt;1&lt;/sup&gt; b.wt.) in EE-treated rats (100 μg kg&lt;sup&gt;1&lt;/sup&gt; 5 days b.wt.) improved serum cholesterol, bile acid and TBIL as well as hepatic SOD and GPx significantly. Also, CWE inhibited ALP, ALT, γ-GT activity as well as levels of TNF-α, NO, MMP-2 and MMP-9 and MDA in comparison with the EE treatment rats. On the other hand, the liver TLR4, NF-κB and p38MAPK gene expression was down regulated group of rats administrated with cranberry extract when compared with the EE-treated rats. CWE's prophylactic action II is more pronounced than prophylactic one. The hepatoprotective effects of cranberry in restoring normal liver functional ability were also supported by histopathological examination of liver tissues. &lt;b&gt;Conclusion:&lt;/b&gt; The results show clearly that cranberry extract has a strong prophylactic effect in EE-induced cholestasis by normalizing the levels of TLR4, NF-κB and p38MAPK gene expression.

LC/MS/MS-Based Liver Metabolomics to Identify Chronic Liver Injury Biomarkers Following Exposure to Arsenic in Rats.

Arsenic is a widespread natural metalloid element. Long-term chronic exposure to arsenic can lead to different degrees of liver injury. Although the etiology of this disease is well known, to date, the underlying mechanism of arsenic-induced liver injury remains unclear, and no specific treatment exists because of the complexity of arsenic. In the present study, potential biomarkers and metabolic pathways in the livers of Wistar rats treated with arsenic for 24weeks were investigated using an integrated metabolic approach with an LC-Orbitrap Q Exactive™ HF-X mass spectrometer. Markedly increased liver levels of arsenic, alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bile acid (TBA) were detected in the arsenic treatment groups (P < 0.05). Furthermore, histopathological examination of liver tissues showed obviously swollen, loose cytoplasm and increased necrosis in the arsenic treatment groups compared with those in the control group (P < 0.05). Metabonomics results showed that 109 metabolites (variable importance in the projection (VIP) > 1; fold change > 2 or < 0.5; P adjusted < 0.05) changed significantly after exposure to arsenic and included 71 upregulated metabolites and 38 downregulated metabolites. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that 6 metabolic pathways with statistical significance-phenylalanine metabolism, pyruvate metabolism, glycolysis/gluconeogenesis, citrate cycle (TCA cycle), thiamine metabolism, and vitamin B6 metabolism-were selected, and 13 differential metabolites were detected to be involved in regulating these metabolic pathways. The present study could help identify potential biomarkers and their functions, as well as metabolic pathways, likely providing evidence for the early diagnosis, prevention, and mechanistic study of arsenism.

Acute in vivo toxicity of neonicotinoid pesticide residues in common Egyptian fruits

Pesticide residues in food is a major health hazard. Contamination of pesticide residues in common Egyptian fruits was studied. Samples of peach and cantaloupe (500g each) from five different local markets were examined. Fruit samples were liquid-liquid extracted. Thiamethoxam was detected in three cantaloupe samples at 0.085 mg/kg and acetamiprid in two samples at 0.24 mg/kg, whereas acetamiprid was detected in all the peach samples at 0.08 mg/kg. Detected levels were below MRL. Male albino rats were given either distilled water (0.2 ml) or acetamiprid (17 µg/kg) or thiamethoxam (6 µg/kg) orally for 6 consecutive days. Doses were calculated according to the estimated average daily intake of fruits (~100 g) and extrapolated to rats. Thereafter, oxidative state of liver and brain was evaluated besides liver function tests and assessment of histopathological features. Serum GPT was in normal range in thiamethoxam-exposed rats, while it showed a marked increase in acetamiprid-exposed rats. sGOT was elevated after exposure to both compounds, though total protein and sGSH were not affected. Oxidative insult was expressed in liver tissue through increased MDA, NO and protein carbonyl contents, although the antioxidant GSH pool was not depleted after pesticide exposure. Acetamiprid boosted the cytokine IL-1 level. Histopathological examination of liver tissue showed inflammatory degenerative changes. Acetamiprid affected the DNA integrity in blood. Brain oxidative state was not changed. These pesticides should be further studied for guiding local regulations towards safer use to avoid long term associated health hazards.

Investigation of the Effect of Lycopene, Hesperidin, Essential Oil and their Relative Nano-Formulation Form on Experimentally Obese –Induced Rats

The study was designed to investigate the effect of lycopene, hesperidin, and essential oil and their nano-formulation form in high-fat diet (HFD) -induced obese Wistar rats. To achieve this, a total of ninety adult Wistar male rats were used. The animals were made obese by feeding rats' high-fat diet (HFD, cholesterol, and bile acid). A dose of cholesterol (30 mg/0.3 mL olive oil /1 kg b.w.) was orally administrated (five times per week ) for 8 consecutive weeks. Obesity was confirmed by the percentages of body weight gain. Animals were divided into negative control groups (normal rats received normal diet) and positive control groups (normal rats received HFD ) and treatment groups (obese rats received different samples) of five animals each. Dose of lycopene and its nanoparticles 50 mg/kg b. wt., hesperidin, essential oil, and their nano-formulation form (100 mg/kg b.wt). All samples and standard drug (orlistat 12 mg/kg b. wt.) were orally administered once daily for four weeks. At the end of experiement, all animal groups were sacrificed and blood samples were collected. Different parameters including total cholesterol, triglycride, HDL-cholesterol, total lipid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinene and urea were determined in the serum. The liver tissue was excised for the determination of hepatic antioxidant biomarkers (catalase and GSH) and oxidative stress (lipid peroxide). Histopathological examination of liver tissue of obese rats showed diffuse fatty liver, circumscribed hepatic vacuoles with prepheralnucleous. However, obese rats- treated with all different samples declaring amelioration in all the measured parameters. The results obtained illustrated that the nano-formulation form are more effective than a native form of lycopene, hesperidin, and essential oil. Besides, the lycopene and its nanoparticles were more effective than hesperidin, essential oil, and their nano-formulation forms. So, it could be concluded that , oral supplementation with lycopene, hesperidin, essential oil, and their relative nano-formulation forms can treat hepatic dysfunction in obese rats.

Panax Ginseng alleviates thioacetamide-induced liver injury in ovariectomized rats: Crosstalk between inflammation and oxidative stress.

Liver diseases impose a substantial health problem. Female hormones play a crucial role in the protection against chronic inflammatory diseases. Fifty female rats were allocated into five groups (n = 10). Group I comprised sham-operated rats. The remaining groups underwent ovariectomy at the beginning of the experiment. Group II served as the ovariectomy-control group. Groups III, IV & V received thioacetamide (TAA; 300 mg/kg; i.p.) to induce liver injury 6 weeks after ovariectomy. Group III served as the TAA-control group. Groups IV & V received panax ginseng (100 and 300 mg/kg/day, p.o.) for 6 weeks post TAA administration. All groups were investigated for liver function tests along with total antioxidant capacity (TAC), tumor necrosis factor-α (TNF-α) and advanced glycation end products (AGEs). Histopathological examination of liver tissues was performed followed by immunohistochemical staining for nuclear factor kappa-B (NF-kβ p65) and myeloperoxidase (MPO). Ovariectomized-rats showed a non-significant change in the measured parameters while TAA administration resulted in significant liver damage. Panax ginseng at both dose levels significantly improved the serum liver function tests and TAC along with decreasing the AGEs and TNF-α. It also restored the histopathological picture of liver tissue and decreased hepatic tissue inflammation via reduction of MPO and NF-kβ p65 immunoreactivity. The current study is the first to elucidate the effect of panax ginseng against TAA-induced liver injury in ovariectomized rats which mimic aged post-menopausal estrogen-deficient females. The study demonstrates the crosstalk between AGEs, NF-kβ and MPO in the modulation of inflammation. Panax ginseng possesses antioxidant and anti-inflammatory properties.

Naringenin alleviates hepatic injury in zinc oxide nanoparticles exposed rats: impact on oxido-inflammatory stress and apoptotic cell death

Human exposure to nanoparticles became unavoidable secondary to their massive involvement in a multitude of industrial applications. Zinc oxide nanoparticles (ZnONPs) are one of the most commonly used metal oxide nanoparticles in biological applications. Naringenin (NAR), a citrus-derived flavonoid, has favorable biological properties that promote human health. The present study was carried out to investigate the possible defensive role of NAR versus ZnONPs provoked hepatic injury in rats through an evaluation of liver enzymes, hepatic biomarkers of oxidative stress, inflammatory process, apoptotic cell death along with histopathological examination of liver tissue. Therefore, 32 adult rats were randomly divided into four equal groups as control, NAR, ZnONPs and co-treated ZnONPs with NAR groups. All treatments were administered for 14 days. Our results showed that ZnONPs induced hepatic injury as documented by the marked increased in hepatic enzymes activities, disturbed hepatic oxidant/antioxidant balance, increased hepatic inflammatory reactions, in addition to, extensive hepatic morphological alterations, marked collagen fibers accumulation as well as overexpression of apoptotic BAX and the noticeable intensified positive nuclear staining for nuclear factor Kabba-b in hepatic tissues. Concurrent NAR supplement to ZnONPs- treated rats significantly declined liver enzymes activities, restored oxidant/antioxidant balance, reversed inflammation, induced fewer collagen fibers accumulation, and antagonized BAX-mediated apoptotic cell death in hepatic tissues. We concluded that concurrent NAR supplement to ZnONPs treated rats improved hepatic function and structure by its antioxidant, anti-inflammatory and antiapoptotic potentials.

The role of different edible vegetable oils as hypolipidemic agents on experimental hyper-lipidemic rat model

Hyperlipidemia is a common disorder that includes genetic and functional disorders represented by elevated lipid levels in the body. The objective of this study was to characterize the physicochemical parameters of the edible seed oils separated from linseed, soybean, olive seed and blends from different proportion, then identify the optimum blend in controlling serum lipid profile in experimental hyperlipidemic rat model. Histopathological examinations of the liver section were carried out to support the laboratory investigation. Sixty male albino rats were used for the study. The animals were divided into ten groups, where group 1 represents negative control, while rats in group 2 received high fat diet and served as positive control. Groups from 3 to 10 were fed high-fat diet and then supplemented with different vegetable oils. At the termination of the 6 weeks trial, blood samples and organs were collected for estimation of lipid profile. Results showed that rats administered different vegetable oils significantly decrease levels of serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) cholesterol as well as increase levels of high-density lipoprotein (HDL) cholesterol in comparison with rats fed high-fat diet. Histopathological examination of liver tissue in positive control showed severe dilatation and congestion in the central vein with fatty change in the surrounding adjacent hepatocytes. While administration of different vegetable oils showed marked improvement in the histological feature of liver tissues. In conclusion, the findings suggest that balanced blend from linseed, soybean and olive oils help in controlling hyperlipidemia and restoring the lipid profile.

Evaluation of the hepatotoxic potential of citalopram in rats

Background and Aims: Citalopram is a selective serotonin reuptake inhibitor with a high potency which is occasionally prescribed and used to treat major depression associated with mood disorders as a first-line drug. According to the results of previous studies, evidence of hepatotoxicity related to citalopram treatment were limited and conflicting. Therefore, we aimed to evaluate the hepatotoxicity potential of sub-chronic citalopram administration. Methods: Citalopram was administered to female rats orally in 5 and 10 mg/kg for 30 days. After the exposure period, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and direct bilirubin levels as biomarkers of hepatotoxicity were measured and histopathological examination of liver tissues was performed. Additionally, GSH levels of liver tissues were determined. Results: The risk of hepatotoxicity related to citalopram was shown by significant increases of serum hepatic biomarkers, AST, ALT, and total bilirubin in citalopram-administered groups. According to the histopathological findings, hepatocellular necrosis, hepatic nuclear asymmetry, and disarrangement of hepatic cord cells (hepatocytes) were prominent in the 10 mg/kg citalopram-administered group. On the other hand, there was no significant difference among the groups in terms of GSH levels. Conclusion: The results suggested that the administration of citalopram might cause hepatotoxic effects, depending on the dose.

Diacerein protects rats with liver ischemia/reperfusion damage: Down-regulation of TLR4/ NFκ-B signaling pathway

PurposeLiver ischemia-reperfusion (I/R) injury is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on liver I/R injury has not yet been fully clarified. Therefore, the current study aimed to detect its hepatic protective effect with the explanation of possible underlying mechanisms. MethodsAdult male albino rats were assigned to 4 groups: sham group, diacerein pretreated sham group, I/R non-treated group, and I/R diacerein pretreated group. Serum liver enzymes, hepatic tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and liver fatty acid binding protein (L-FABP) levels were determined. Histopathological examination of liver tissues and immunohistochemical studies of heat shock protein 70, nuclear factor-kappa B, and Cluster of Differentiation 68 were also done. ResultsDiacerein pretreatment has the ability to restore the hepatic I/R damaging effect, proved by the reduction of serum liver enzymes, the decrease of the oxidative stress and hepatic inflammation via down-regulation of TLR4/ NFκ-B signaling pathway together with the restoration of L-FABP level and improvement of the histopathological and immunohistochemical study findings in the hepatic tissue. ConclusionThese results suggested the hepatoprotective effect of diacerein relies on its antioxidant and anti-inflammatory effects reducing TLR4/ NFκ-B signaling pathway.

Preventive Role of Soy Protein in Fructose Induced Metabolic Dysfunction in Rats via Inhibition of Nuclear Factor kappa B Pathway

Soy protein is an important component of soybeans that has beneficial role in improving insulin resistance. Nuclear factor kappa B (NF-κB) is a crucial pathway that has been implicated in the development of metabolic syndrome. Our study aimed to examine the protective effect of soy protein isolate - as a natural NF-κB inhibitor - and its possible mechanism of action in amelioration of inflammatory and metabolic disorders induced in male albino rats by high fructose diet (10% w/v) via using synthetic NF-κB inhibitor (IMD-0354). Rats were randomized into normal control group, soy group, NF-κB inhibitor (IMD-0354) group, high fructose group, high fructose with soy group, high fructose with NF-κB inhibitor group, high fructose with soy and NF-κB inhibitor group. Serum glucose, serum insulin, serum free fatty acids, insulin resistance (HOMA-IR), NF-κB, phosphorylated insulin receptor (pISR), carbohydrate-responsive element-binding protein (ChREBP) were determined and histopathological examination of liver tissue was performed. The concurrent administration of IMD-0354 and/or soy protein with high fructose significantly increased pISR and decreased FFAs, NF-κB, glucose, insulin, HOMA-IR, and ChREBP as well as improved the pathological conditions of the livers. The metabolic and inflammatory disorders induced by chronic consumption of fructose could be inhibited by co-administration of soy protein through regulation of NF-κB signalling pathway.

Epigenetic Programming Through Breast Milk and Its Impact on Milk-Siblings Mating

BackgroundThe epigenetic effects of transmission of certain regulatory molecules, such as miRNAs, through maternal milk on future generations, are still unknown and have not been fully understood yet. We hypothesized that breastfeeding regularly by adoptive-mother may cause transmission of miRNAs as epigenetic regulating factors to the infant, and the marriage of milk-siblings may cause various pathologies in the future generations.ResultsA cross-fostering model using a/a and Avy/a mice had been established. F2 milk-sibling and F2 control groups were obtained from mating of milk-siblings or unrelated mice. Randomized selected animals in the both F2 groups were sacrificed for miRNA expression studies and the remainings were followed for phenotypic changes (coat color, obesity, hyperglycemia, liver pathology, and life span). The lifespan in the F2 milk-sibling group was shorter than the control group (387 vs 590 days, p = 0.011) and they were more obese during the aging period. Histopathological examination of liver tissues revealed abnormal findings in F2 milk-sibling group. In order to understand the epigenetic mechanisms leading to these phenotypic changes, we analyzed miRNA expression differences between offspring of milk-sibling and control matings and focused on the signaling pathways regulating lifespan and metabolism. Bioinformatic analysis demonstrated that differentially expressed miRNAs were associated with pathways regulating metabolism, survival, and cancer development such as the PI3K-Akt, ErbB, mTOR, and MAPK, insulin signaling pathways. We further analyzed the expression patterns of miR-186-5p, miR-141-3p, miR-345-5p, and miR-34c-5p and their candidate target genes Mapk8, Gsk3b, and Ppargc1a in ovarian and liver tissues.ConclusionOur findings support for the first time that the factors modifying the epigenetic mechanisms may be transmitted by breast milk and these epigenetic interactions may be transferred transgenerationally. Results also suggested hereditary epigenetic effects of cross-fostering on future generations and the impact of mother-infant dyad on epigenetic programming.