Histopathological Examination Of Liver Tissues Research Articles

Hepatoprotective effects of ethanolic extract of Corallocarpus epigaeus roots on nitrobenzene-induced liver injury in Wistar rats

ABSTRACT This study examined the potential of Corallocarpus epigaeus ethanolic root extract to combat free radicals using DPPH, FRAP, hydroxyl radical, hydrogen peroxide, and nitric oxide scavenging assays. Rats were initially exposed to a single oral dose of nitrobenzene (50 mg kg−1 body weight), followed by a 15-d oral regimen of the ethanolic root extract of C. epigaeus at 200 mg kg−1 body weight. The assessment of serum liver marker enzymes (AST, ALT, and ALP), lipid peroxidation levels, antioxidant enzyme activities, and histopathological examinations of liver tissues were carried out. The C. epigaeus ethanolic root extract demonstrated antioxidant properties and contained flavonoids, tannins, carotenoids, lycopene, and phenolic compounds. In Nitrobenzene-induced rats, elevated serum markers and increased liver lipid peroxidation were observed that were normalized by the extract. It also increased antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase. Histopathological analysis confirmed the hepatoprotective effects of the extract.

Thyme and Oregano Oil Potential Therapeutics against Malathion Toxicity through Biochemical, Histological, and Cytochrome P450 1A2 Activities in Male Wistar Rats.

The widespread use of malathion may offer several hazards to humans and animals; additionally, many medicinal plants provide what is known as a broad antitoxicity treatment. This study was carried out to investigate hazardous biochemical and histological reactions to MOP and evaluate the effectiveness of TEO and OEO essential oils in restoring normal physiological conditions after MOP exposure by measuring enzyme-specific activity for Cytochrome P450 1A2 (CYP1A2). One hundred and twenty rats were divided into six groups of twenty animals each: (i) C - MOP served as the control group, (ii) C + MOP treated with 5 mg/kg/BW of Malathion-D10, (iii) TEO treated with 100 mg/kg/BW of oregano essential oil, (iv) TEO treated with 100 mg/kg/BW of thyme essential oil, (v) MOP + OEO treated with 5 mg/kg/BW of Malathion-D10 and 100 mg/kg/BW of oregano essential oil, and (vi) MOP + TEO treated with 5 mg/kg/BW of Malathion-D10 and 100 mg/kg/BW of thyme essential oil. The results indicated the protective effects of OEO and TEO against MOP-induced weight loss. Additionally, there was a significant improvement in ALT, AST, and ALK-Ph after being treated with OEO and TEO, either alone or after MOP exposure. Also, treatment with OEO and TEO ameliorated these oxidative stress parameters, indicating their antioxidative properties. A histopathological examination of liver tissues showed reduced hepatocellular damage and improved liver architecture in the OEO and TEO, both alone and in combination with MOP, and protective effects were more pronounced in the TEO-treated groups. However, the results indicated that TEO was more effective than OEO in increasing CYP1A2 expression and alleviating MOP-induced toxicity. Specifically, TEO showed higher protein expression and therapeutic action in reducing liver damage. In conclusion, these findings suggest that OEO and TEO may be potent therapeutic agents against MOP toxicity, offering protective effects by enhancing CYP1A2 activity and mitigating organ damage. Such knowledge would be an important step toward developing potentially unique treatment options for natural antitoxins.

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

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

Haematological and biochemical studies on Justicia secunda infusion used in treatment of anaemia

The effect of ethanolic and infusion of Justicia secunda leaves in the animal organs was investigated using standard analytical protocols. A total of 40 albino rats divided into four groups of five rats each comprising one normal groups and three groups treated with 125, 250 and 500mg/kg body weight respectively. The infusion of J. secunda leaves was prepared using conventional methods. The hematological, biochemical and histological studies were also carried out as reported in previous literatures. The findings confirmed that Justicia secunda leaves are not toxic at the doses administered, there were significant concentrations of essential minerals such as sodium, potassium, calcium, iron, phosphorus, and sulfur. The hematological study conducted on the infusion of the leaves revealed several positive effects on blood parameters in experimental rats. The extract significantly P<0.05 elevated hemoglobin and platelet count, particularly at higher doses, compared to the control group. The liver function tests showed no significant alterations in AST, ALT, TP, and ALB levels; however, the infusion resulted in some alterations in ALP activity and total bilirubin concentration. The histopathological examination of liver tissues showed mild congestion and degenerative changes in higher dose groups, indicating potential dose-dependent hepatomegaly and stress on hepatic architecture.

Flavone improves liver damage in nicotine-exposed rats via the Nrf2/HO-1 pathway

Objective: To assess the hepatoprotective effects of flavone on nicotine-induced liver damage. Methods: Thirty-six rats were allocated into six groups: the control group, the nicotine group, the flavone alone groups (10 and 25 mg/ kg/body weight), and the nicotine groups treated with flavone (10 and 25 mg/kg/body weight). Liver function, oxidative stress, Nrf2 pathway (HO-1, Nrf2, and Keap-1), and inflammatory markers (IL-17, TNF-α, and NF-κB) were evaluated. Additionally, a histopathological examination of liver tissues was performed. Results: Nicotine increased liver damage, inflammation, and oxidative stress. However, flavone suppressed nicotine-induced liver enzymes, oxidative stress, and inflammation, as manifested by increased antioxidants and decreased malondialdehyde level, liver enzymatic activities, and inflammatory markers. Flavone (10 and 25 mg/kg/body weight) also reduced the level of Keap-1 and increased HO-1 and Nrf2 levels in the liver of nicotine-exposed rats. Conclusions: Flavone has hepatoprotective properties and may slow the progression of liver injury by reducing oxidative stress, liver enzymes, and inflammation possibly via the Nrf2 pathway.

Reveal the mechanism of hepatic oxidative stress in mice induced by photo-oxidation milk using multi-omics analysis techniques

IntroductionPhoto-oxidation is recognized as a contributor to the deterioration of milk quality, posing potential safety hazards to human health. However, there has been limited investigation into the impact of consuming photo-oxidized milk on health. ObjectivesThis study employs multi-omics analysis techniques to elucidate the mechanisms by which photo-oxidized milk induces oxidative stress in the liver. MethodsMouse model was used to determine the effect of the gavage administration of milk with varying degrees of photo-oxidation on the mouse liver. The damage degree was established by measuring serum markers indicative of oxidative stress, and with a subsequent histopathological examination of liver tissues. In addition, comprehensive metabolome, lipidome, and transcriptome analyses were conducted to elucidate the underlying molecular mechanisms of hepatic damage caused by photo-oxidized milk. ResultsA significant elevation in the oxidative stress levels and the presence of hepatocellular swelling and inflammation subsequent to the gavage administration of photo-oxidized milk to mice. Significant alterations in the levels of metabolites such as lumichrome, all-trans-retinal, L-valine, phosphatidylglycerol, and phosphatidylcholine within the hepatic tissue of mice. Moreover, photo-oxidized milk exerted a pronounced detrimental impact on the glycerophospholipid metabolism of mice liver. The peroxisome proliferator-activated receptors (PPAR) signaling pathway enrichment appreciated in the animals that consumed photo-oxidized milk further supports the substantial negative influence of photo-oxidized milk on hepatic lipid metabolism. Gene set enrichment and interaction analyses revealed that photo-oxidized milk inhibited the cytochrome P450 pathway in mice, while also affecting other pathways associated with cellular stress response and lipid biosynthesis. ConclusionThis comprehensive study provides significant evidence regarding the potential health risks associated with photo-oxidized milk, particularly in terms of hepatic oxidative damage. It establishes a scientific foundation for assessing the safety of such milk and ensuring the quality of dairy products.

Effects of mesenchymal stem cells versus curcumin on sonic hedgehog signaling in experimental model of Hepatocellular Carcinoma.

Sonic Hedgehog (SHH) is a fundamental signaling pathway that controls tissue reconstruction, stem cell biology, and differentiation and has a role in gut tissue homeostasis and development. Dysregulation of SHH leads to the development of HCC. The present study was conducted to compare the effects of mesenchymal stem cells (MSCs) and curcumin on SHH molecular targets in an experimental model of HCC in rats. One hundred rats were divided equally into the following groups: control group, HCC group, HCC group received MSCs, HCC group received curcumin, and HCC group received MSCs and curcumin. Histopathological examinations were performed, and gene expression of SHH signaling target genes (SHH, PTCH1, SMOH, and GLI1) was assessed by real-time PCR in rat liver tissue. Results showed that SHH target genes were significantly upregulated in HCC-untreated rat groups and in MSC-treated groups, with no significant difference between them. Administration of curcumin with or without combined administration of MSCs led to a significant down-regulation of SHH target genes, with no significant differences between both groups. As regards the histopathological examination of liver tissues, both curcumin and MSCs, either through separate use or their combined use, led to a significant restoration of normal liver pathology. In conclusion, SHH signaling is upregulated in the HCC experimental model. MSCs do not inhibit the upregulated SHH target genes in HCC. Curcumin use with or without MSCs administration led to a significant down-regulation of SHH signaling in HCC and a significant restoration of normal liver pathology.

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.