Histopathological Changes In Liver Research Articles

A histopathological and stereological study of the effects of acetylsalicylic acid on doxorubicin-induced hepatotoxicity in mice

ABSTRACT Doxorubicin (Dox) is an anthracycline antibiotic with antineoplastic activity. Acetylsalicylic acid (Asa) is recommended for use as a prophylactic for thromboembolism during treatment of cancers. We investigated liver toxicity due to combined use of Dox and Asa in chemotherapy regimens. We used 140 Swiss albino mice divided into four main groups: control, Dox, Asa, and Dox + Asa. Each group was subdivided into seven subgroups based on time of sacrifice, i.e., 6, 12, 24, 48 h and 7, 14, 21 days. Quantitative and histopathological changes in liver were assessed by light microscopy and stereology. The portal triad area of the Dox and Dox + Asa groups was increased significantly compared to controls at 6 h, whereas in the Asa group, the means were similar to controls. Assessment of histopathology indicated an increased time-dependent degeneration and necrosis of liver tissues in mice in the Dox and Dox + Asa groups. The protective effects of Asa were not evident in Dox + Asa group. When Dox and Asa were administered together, degenerative changes were greater than for in the group that was given Dox alone. We found that Asa and Dox combined therapy increased tissue damage.

Histology of Liver of the Deceased Due to Harmful Use of Alcohol.

To study types and incidence of histological changes in liver of people deceased due to harmful use of alcohol. A retrospective review of medico-legal autopsy of 236 adults who died in the years 2015-2016 due to harmful use of alcohol was done. Histopathological liver samples taken during autopsies were evaluated. Blood alcohol content was analyzed. Serological tests for hepatitis B surface antigen and anti-hepatitis C virus (HCV) were performed. The most common liver pathology (83.1%) was steatosis, mainly mixed type (50%); 66.9% had high-grade steatosis. Liver fibrosis was detected in 39.4% of cases, with fibrosis of higher than or equal to third grade in 14%, hepatitis in 44.5% and steatohepatitis in 19.1%. Toxic hepatocyte injury features (ballooning degeneration, Mallory-Denk bodies) were found in 20.8% cases and degenerative-damage changes in 41.1%. The correlation between the grade of steatosis and fibrosis (P=0.0005), toxic injury (0.00000101) and degenerative-traumatic changes (P=0.00000741) was found. The correlation was found between hepatitis and higher than or equal to third grade steatosis (P=0.037), cholestasis (P=0.0139), toxic injury features (P=2.58×10-13), degenerative-damage changes (P=7.9×10-12) and presence of anti-HCV (P=0.00723) and between progression of fibrosis and presence of toxic injury features (2.28×10-19), degenerative-damage changes (P=4.25×10-11) and anti-HCV (P=0.0263). Spectrum of histopathological liver changes is broad regardless of sex, and various traits are present in various patterns. Comorbidities have strong influence on the picture of changes in the liver. Exact evaluation how often and what histopathological changes will develop in alcohol liver disease is not possible by reason of variability of external factors.

Potential attenuation of biochemical parameters and enzymatic functions in Cyprinus carpio fingerlings by Phenthoate 50 EC insecticide exposure.

The risks of the health-associated problems of pesticide-exposed non-target organisms are ubiquitous, therefore an emerging concern to strike the balance between benefit and risk factors. In the present study, by elucidating multiple biomarkers, the effects of Phenthoate 50 EC on the acute toxicity tests and different pathophysiological changes of common carp (Cyprinus carpio) fingerlings were studied in time- and concentration-dependent manners. The LC50 of Phenthoate 50 EC for the fish was 7.39 (6.716-8.076) ppm at 96h. As an indicator of neurotoxicity, compared to the control group, significant (P < 0.01) reduction in brain acetylcholinesterase (AChE) activity was observed, whereas plasma glutamate-oxalacetate transaminase (PGOT) and plasma glutamate pyruvate transaminase (PGPT) activities were increased significantly (P < 0.01) at the doses of 2.22 and 3.69ppm of Phenthoate 50 EC, respectively. Histopathological changes in the insecticide-treated fish liver suggested the hepatic tissue damages, while alteration of the blood, gills and kidney morphology; progressive decrease (P < 0.05) in the serum calcium levels; and significantly (P < 0.01) decreased blood glucose level at 2.22 and 3.69 or 5.17ppm of Phenthoate 50 EC demonstrated the oxidative stress and requirement of the up-surging energy demands due to the exposure of this organophosphate chemical. These results advice the modulation caused by this widely used agrochemical on the physiology of aquatic fauna by changing the enzymatic and biochemical indices at cellular level.

Histopathological changes in liver and kidney of sharptooth catfish fed on cooked Jatropha curcas seedmeal based diets

Introduction: Histology of the organs of fish species is important in the understanding of the pathological changes related to nutritional sources. This study evaluates the histopathological alteration in the liver and kidney of sharptooth catfish fed diets containing Jatropha curcas seedmeal in a 56-day feeding trial. Methods: Clarias gariepinus fingerlings of average weight 2.61±0.02g were acclimatized for a week, and allotted into five dietary treatments; containing 0, 25, 50, 75 and 100% Jatropha curcas seedmeal replacement levels for soybean meal respectively. Each treatment was replicated three times with fifteen fish per replicate. Fish were fed 5% body weight on two equal proportions per day. Histological assessment was conducted using standard procedure. Results: There were no lesions on the photomicrographs of the kidney of fish exposed to all the dietary treatments while moderate vacuolation of the hepatocytes was observed in the liver of fish fed diet D1-control diet. There were very prominent melanomicrophage centres in the liver of Clarias gariepinus fed test diet D3 with some hepatocytes which appeared vacuolated. The trend of vacuolation of hepatocytes of the liver among some treatments were not dietary related as no visible lesions were seen in the liver of fish fed test diets D2 ; D4 and D5. Significance: This study established that Jatropha curcas based diets exert hepatoprotective effect on the liver of fish fed with the diets.

Effect of the addition of essential fatty acid mixture to the drinking water of the heat stress broilers on adipokine (Apelin, BDNF) response, histopathologic findings in liver and intestines, and some blood parameters

The purpose of this study was to examine the effect of adding an essential fatty acid mixture (EOM; Eucalyptus globulus Labill, thymus vulgaris, Cymbopogon nardus, and Syzygium aromaticum) to the drinking water in the heat stress broilers on the adipokine (Apelin, BDNF) response, the histopathologic changes in liver and intestines, and some biochemical parameters. This study lasted for a total of 42 days, including the physical exercise period (7 days) and the fattening period (35 days). A total of 400 Ross 308 male broilers (1-d-old) were randomly divided into 8 groups (50 animals per group), each of which was exposed to various conditions of temperature (C: 22 °C and SC: 36 °C) and treatment dose (C, 250, 500 and 750 mL/1000 L). Each group was divided into 5 subgroups, each comprising 10 animals. In the stress-free groups, whereas the Apelin level linearly decreased, the BDNF level linearly increased. In histopathology, the liver tissue was found to be normal in all groups whereas the duodenum villi length was found to increase in the group of 750 mL/1000 L. No statistically significant difference was found between the stressed groups and the non-stressed groups in terms of VLDL, Glucose, Total bilirubin, ALT, and TG (p > .05). While Apelin level increased in the stressed groups, the BDNF level increased in the group of 250 mL/1000 L. In the histopathological examination, a small amount of coagulation necrosis was detected in hepatocyte, a diffuse hydropic degeneration was observed in hepatocytes, and finally a dilatation and hyperaemia were seen in sinusoid in the groups of EOM-500 mL/1000 L and EOM-750 m/1000 L compared to the control group. Whereas there was no difference between the group of EOM-250 mL/1000 L and the control group in terms of duodenum villa length, there was a significant decrease in other groups (p < .00). In conclusion, this study showed that adding 250 mL/1000 L of EOM to the drinking water had a positive effect on the serum levels of Apelin and p-BDNF in the groups exposed to stress (p <.05). HIGHLIGHTS Heat stress results in serious annual economic losses in the poultry industry. Essential oil fatty mix acids have positive effects on poultry health. Apelin and BDNF may be a protective factor against deleterious consequences of chronic exposition to heat stress

Anti-obesity activity of gold nanoparticles synthesized from Salacia chinensis modulates the biochemical alterations in high-fat diet-induced obese rat model via AMPK signaling pathway

Salacia chinensis (SC) is generally known as Saptrangi, which has been used as an herb in Ayurvedic medicine and has a broad range of biological applications. The current research was planned to develop Salacia chinensis-loaded gold nanoparticles (SC-AuNPs) and to assess the anti-obesity parameters in a high-fat diet (HFD) treated obese rats. SC-AuNPs were synthesized and characterized using UV–visible spectroscopy, SEM, FTIR, EDX, XRD, and TEM. Furthermore, the bodyweight changes, BMI, adipose index, leptin, resistin, adiponectin, AI, CRI, liver marker enzymes, inflammatory markers, lipid profile, AMPK signaling proteins, and liver histopathological changes were analyzed. We observed that the synthesized SC-AuNPs had a spherical shape, crystalline nature, and possessed a different functional group. The SC-AuNPs treatments also decreased body weight, BMI, adipose index, leptin, resistin, AI, CRI, liver marker enzymes, lipid profile, inflammatory markers, and AMPKα1. On the other hand, SC-AuNPs treatment increased adiponectin, HDL-C, and pAMPKα1. The histopathological findings showed improved result with reduced hepatocyte degradation under the influence of SC-AuNPs treatment.

Ischemic Preconditioning Protects Against Hepatic Ischemia-Reperfusion Injury Under Propofol Anesthesia in Rats

BackgroundPropofol is widely used in general anesthesia, and it has been reported to protect various organs against ischemia-reperfusion injury (IRI), including liver. To evaluate the hepatoprotective effects of ischemic preconditioning (IP) under propofol anesthesia, we investigated the possible underlying mechanisms in rats. MethodsMale Sprague–Dawley rats were randomly assigned to 3 groups: sham group (n = 5), non-IP group (n = 9; 45 minutes of hepatic ischemia followed by 2 hours of reperfusion), and IP group (n = 9; IP applied as 10 minutes of hepatic ischemia followed by 15 minutes of reperfusion before 45 minutes of ischemia). Anesthesia was maintained with intravenous (IV) infusion of propofol (800 μg/kg/min). Liver enzymes, histopathological changes, and cytokine expression were examined. ResultsThe IP group showed significantly lower liver enzyme levels (aspartate aminotransferase, P = .045; alanine aminotransferase, P = .006) and reduced the histologic grades of hepatic injury 2 hours after reperfusion (P = .004) compared to the non-IP group. Lactate dehydrogenase activity (P < .001) and interleukin-6 mRNA levels were significantly higher in the non-IP group than in the sham and IP groups (P = .002, both groups). ConclusionsOur results demonstrate that IP under propofol anesthesia significantly attenuated hepatic IRI. The principal mechanism of the protective effects appeared to involve reduced expression of the IL-6 pro-inflammatory cytokine and subsequent reduction of the degree of necrosis.

Preventive effect of Euphorbia royleana Boiss on diabetes induced by streptozotocin via modulating oxidative stress and deoxyribonucleic acid damage

Oxidative stress is associated with streptozotocin induced diabetes. The present study was conducted to investigate the anti-oxidant, anti-diabetic and genotoxic effects of Euphorbia royleana Boiss. stem’s crude extract in rats. Better inhibitory concentration (IC50) of methanolic extract in alpha amylase and antioxidant assays along with improvement in hyperglycemia can be linked with the presence of phenolic acids and flavonoids determined quantitatively by HPLC. The declining superoxide dismutase, catalase activities, and hydrogen peroxide concentrations were restored at the dose of 500 mg/kg. The methanolic extract turned out to be Class I genotoxic at 100 µg/mL. Moreover, improvement in histopathological changes of pancreas, liver and kidney were also observed.

Effects of heavy metal pollution on hepatosomatic ındex and vital organ histology in Alburnus mossulensis from Karasu River

In this study, histological effects of water pollution to freshwater cyprinid, Alburnus mossulensis, was investigated. Water, sediment, and fish samples were taken from four stations in Karasu River (Erzurum, Turkey) between June and September in 2015? 2016. In water and sediment samples, the concentrations of Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Br, Sr, and Pb were detected. Histopathological changes in gill, liver, and kidney tissues were determined by degree of tissue change (DTC), and hepatosomatic index (HSI) was calculated. The mean concentrations of heavy metals in water and sediment samples were lower at station 4. The trend of some metal contents found in the fish was in increasing order of Zn < Cu < Cr < Pb. The observations on histopathology included cellular degeneration, congestion, dilatation, vacuolization, edema, vasodilatation, hyperplasia, hypertrophy, infiltration, melanomacrophage aggregates, glomerulopathy, fibrosis, and necrosis. It was observed that the DTC and HSI values in fish varied significantly from station to station. The results showed that the higher severity of histopathological alterations in the fish tissues was strongly correlated with agricultural and domestic activities in the area.

Mechanism of psoralen in aggravating hepatotoxicity induced by CCl_4 by delaying liver regeneration

This study aimed to investigate whether psoralen can aggravate hepatotoxicity induced by carbon tetrachloride(CCl_4) by inducing hepatocyte cycle arrest and delaying liver regeneration. Female C57 BL/6 mice aged 6-8 weeks were randomly divided into control group, model group(CCl_4 group), combined group(CCl_4+PSO group) and psoralen group(PSO group). CCl_4 group and CCl_4+PSO group were given CCl_4 intraperitoneally at a dose of 100 μL·kg~(-1) once; olive oil of the same volume was given to control group and PSO group intraperitoneally; 12 h, 36 h and 60 h after CCl_4 injection, PSO group and CCl_4+PSO group were administrated with PSO intragastrically at a dose of 200 mg·kg~(-1); 0.5% CMC-Na of the same volume was administrated to control group and PSO group intragastrically. The weight of mice was recorded every day. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were measured at 36 h, 60 h and 84 h after CCl_4 injection. Mice were sacrificed after collection of the last serum samples. Liver samples were collected, and liver weight was recorded. Histopathological and morphological changes of liver were observed by haematoxylin and eosin staining. The mRNA levels of HGF, TGF-β, TNF-α, p53 and p21 in liver were detected by RT-qPCR. Western blot was used to detect the levels of cell cycle-related proteins. According to the results, significant increase of serum ALT and AST and centrilobular necrosis with massive inflammatory cell infiltration were observed in CCl_4+PSO group. After PSO administration in CCl_4 model, the mRNA levels of HGF(hepatocyte growth factor) and TNF-α were reduced, while the mRNA expressions of TGF-β, p53 and p21 was up-regulated. The expression of PCNA(proliferating cell nuclear antigen) was significantly increased in CCl_4 and CCl_4+PSO group, while the relative protein level in CCl_4+PSO group was slightly lower than that in CCl_4 group. Compared with control and CCl_4 group, the expression of p27(cyclic dependent kinase inhibitor protein p27) was prominently increased in CCl_4+PSO group. These results indicated that hepatotoxicity induced by CCl_4 could be aggravated by intraperitoneal administration with PSO, and the repair process of liver could be delayed. The preliminary mechanism may be related to the inhibition of PCNA and regulation of some cell cycle-associated protein by psoralen, in which the significant up-regulation of p27, p53 and p21 may play important roles.

Pyrazinamide alleviates rifampin-induced steatohepatitis in mice by regulating the activities of cholesterol-activated 7α-hydroxylase and lipoprotein lipase

The combination of rifampin and pyrazinamide is commonly used in the clinical treatment of tuberculosis, but its safety needs to be further clarified. Mice were intragastric administration of rifampin 300 mg/kg, pyrazinamide 625 mg/kg, rifampin 300 mg/kg plus pyrazinamide 625 mg/kg. The results showed that rifampin significantly increased transaminases, TBIL and TBA levels in serum, increased TG, TC content, HMGCR and CYP7A1 protein, CYP7A1, FGFR4, PXR, FAS and FXR mRNA expression, but decreased the level of SREBP-1c mRNA and induced severe steatohepatitis and hepatocyte necrosis in liver in mice. While pyrazinamide can improve many abnormal indexes when it used with RFP, including liver histopathology, liver TG, TC level and serum biochemistry, GPHBP1, FAS and CYP7A1 mRNA, LPL protein expression and activity induced by rifampin. However, pyrazinamide alone significantly decreased liver TG levels and caused only slight inflammatory pathological changes in liver histopathology in mice. These data suggested that rifampin increases TG and TC levels in the liver may be related to activate HMGCR, CYP7A1, PXR and FXR, theses toxic actions of rifampin were alleviated by pyrazinamide may be due to inhibite the activity of CYP7A1, PXR and FAS, and increasing the LPL protein expression and activity.

Quercetin attenuates NLRP3 inflammasome activation and apoptosis to protect INH-induced liver injury via regulating SIRT1 pathway

Severe hepatotoxicity greatly limits the clinical application of the first-line anti-tuberculosis drug isoniazid(INH). Quercetin(Que) has multiple pharmacological properties, and is regarded as a potential protective agent against a variety of organ injuries. However, the exact effect of quercetin on INH-induced hepatotoxicity and the underlying mechanisms are not yet completely understood. In this study, liver injury models were established in rats and L02 cells toreveal the protective effect of Que on INH-induced hepatotoxicity and the relevant mechanism. The in vivo results indicated that Que pretreatment reduced the level of ALT/AST, improved the liver histopathological changes and substantially mitigated apoptosis in rats. In vitro, it evidently relieved INH-induced cell viability loss and apoptosis in L02 cells. Furthermore, thestudiesonmechanisms elucidated that Que remarkably elevated the expression of SIRT1 and suppressed NLRP3 inflammasome activation. Meanwhile, Que significantly inhibited the level of tumor suppressor P53, Bax, cleaved-cas3 expressionl and increased Bcl-2 expression to reduce apoptosis in vivo and in vitro. However, SIRT1 inhibitor EX527 reversed the suppression of Que on NLRP3 inflammasome activation and the protection of Que on rat liver injury and cell apoptosis. In short, our findings showed that Que exhibited protective effects against INH-induced liver damage via inhibiting the activation of NLRP3 inflammasome and apoptosis in a SIRT-dependent manner.

Protective effect of Antigonon leptopus (Hook et. Arn) in cadmium induced hepatotoxicity and nephrotoxicity in rats

BackgroundAntigonon leptopus is a medicinal plant its leaves has not been reported for protective effects against cadmium induced hepatorenal toxicity. Cadmium (Cd) is a non-essential toxic metal used in industrial process, causes severe risk to human health with high levels. It is accumulated primarily in liver and kidney.MethodsMale Wistar albino rats (200-250 g) were divided into 6 groups (n = 6) and had free access to diet and water. Cadmium chloride (5 mg/kg b.w/day) was administered orally for 21 days and methanolic extract of Antigonon leptopus (ALME) was administered to groups of cadmium treated rats at daily doses of 100, 200 and 400 mg/kg b.w;p.o. for 21 days. At the end, liver and kidney markers along with antioxidant parameters are evaluated.ResultsThe results indicated that, administration of cadmium significantly (p < 0.05) increased the levels liver enzymes in serum and bilirubin levels, decreases in total proteins and albumin; in addition to the levels of uric acid, urea and creatinine were increased in the serum. Glutathione (GSH) levels and the enzyme catalase activities were significantly(p < 0.05) decreased while lipid peroxidation was increased in hepatic and renal tissues of cadmium treated rats. The pre-administration of ALME at all the three test doses, alleviated hepatorenal toxicity in cadmium treated rats, used Silymarin (100 mg/kg) as standard. Moreover, ALME treatment was able to reverse the histopathological changes in liver and kidney tissues, and increased the red blood cells, hemoglobin content and decreased prothrombin time and white blood cells.ConclusionAmong all the three test doses, ALME at 200 mg/kg have shown significant antioxidant effect and also exerts beneficial effect against cadmium induced hepatorenal toxicity.

SGLT2 Inhibitor Treatment Outcome in Nonalcoholic Fatty Liver Disease Complicated with Diabetes Mellitus: The Long-term Effects on Clinical Features and Liver Histopathology.

Objective The aim of this study was to determine the long-term effects of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) in nonalcoholic fatty liver disease (NAFLD) patients with type 2 diabetes mellitus (T2DM) on the clinical features and liver histopathology. Methods In this retrospective study, the long-term histological impacts of SGLT2i in NAFLD patients with T2DM were investigated. Patients Seven patients with NAFLD and T2DM were treated for the long term with 100 mg/day canagliflozin, an SGLT2i, and liver biopsies were obtained at the 3 points of pretreatment, 24 weeks, and ≥1 year (third liver biopsy) after the start of treatment. Six of seven patients were evaluated with third liver biopsy at the point of three or more years. The primary outcome was liver histopathological changes (defined as a decrease in the NAFLD activity score of one point or more without worsening of the fibrosis stage, compared to pretreatment). Results All 7 patients showed worsening of body mass index and waist circumference at the third liver biopsy compared to 24 weeks. However, the scores of steatosis, lobular inflammation, ballooning, and fibrosis stage improved at the third liver biopsy in 57%, 43%, 14%, and 29% of the patients, respectively, compared to pretreatment. One of the seven patients showed histopathological worsening at the third liver biopsy compared to pretreatment, but the improvement was maintained in the other six patients. Conclusion The long-term treatment of NAFLD complicated by T2DM using an SGLT2i is associated with long-term improvement in liver histopathology despite the worsening of clinical features.

Protective Therapy with Mitochondria Isolated from Mesenchymal Stromal Cells in a Sepsis Model

Background & Aim In vivo mitochondrial transfer of mesenchymal stromal cells (MSCs) to immune cells, alveolar and bronchial epithelial cells resulted in metabolic and functional improvements. Thus, we hypothesized that naked mitochondria isolated from MSCs can be internalized by pulmonary structural cells and could be used as systemic therapy in a sepsis model. Methods, Results & Conclusion MSCs-derived mitochondria were incubated with septic murine lung endothelial and epithelial cells. Mitochondrial internalization was assessed by fluorescence microscopy, and its impact on oxidative stress and cellular respiration were evaluated. C57Bl6 mice were divided into control group, sepsis group (CLP, cecal ligation and puncture) and sepsis group with mito-treatment (CLP-mito, intravenous administration of mitochondria derived from 3 × 106 MSCs, 24 hours after CLP). The effects on mortality, pulmonary function and morphometry, liver and kidney histopathological and molecular changes were evaluated after 24 hours of mito-treatment. Mitochondria internalization by septic endothelial and epithelial cells led to reduce oxidative stress which was increased by 250% in endothelial cells and 150% in epithelial cells in CLP mice compared to control. Likewise, by oxygraphy, we analyzed the rate of oxygen consumption (OCR) of these cells. We have seen that, in epithelial cells, only maximal (MR) repolarization was reduced by about 30% after sepsis. In endothelial, both basal (BR) and maximal respiration (MR) were reduced by 50 and 48% respectivelly after sepsis, as well as a significant increase in the proton-leak (PL) rate in relation to the control group (33%). In both cell types, the altered parameters were re-established at control levels after mitocondrial treatment. Mito-treatment induced higher survival rates (60%) and reduced lung elastance (24%). Lung morphometry analysis demonstrated that mito-treatment reversed increases found in septic animals in alveolar collapse (230%), lung neutrophils (90%), lung collagen collagen (300%), elastogenesis (38%). Histological analysis of the liver demonstrates the increase of vacuolization (210%) and inflammatory infiltrate (105%) in septic animals, which were completely normalized after mito-treatment. Treatment also improved sepsis-induced kidney brush border damage (350%) and interstitial edema (205%). This work demonstrates the ability to internalize mitochondria isolated from MSCs by structural cells and the therapeutic potential of mito-treatment in a sepsis model.

Hepatorenal Effects of Silver Nanoparticles in In-Vivo Postnatal Model of Toxicity and in HepG2 Cell Line

Silver nanoparticles (Ag-NPs) had many uses in medicine, household and industry. To better understand the postnatal toxicity of Ag-NPs in lactating female rats and its offspring’s, 18 female rats after delivery were divided into three groups and dams received orally the AG-NPs at doses of 0, 50, 100 ppm daily for 21 days. After the end of treatment, all rats were euthanized and blood and tissues were separated for evaluation of biochemical and histopathology in dams and its pups. The Ag-NPs had no effect on the dam's weight while the reduction of rats’ pups weight was noticed after first week only after the treatment. Notably, Ag-NPs had toxic effects in rat’s pups, as well as its dam with evidence of elevation of liver enzymes, urea, creatinine and reduction of serum protein, albumin and globulin and considered the first report explained the toxicity in the rat’s pups. Moreover, rats' pups revealed histopathological changes in liver and kidney as well as its dams. Notably, the nano-silver is considered cytotoxic for HepG2 cell line as well as mouse liver cell line. In conclusions, the Ag-NPs considered toxic in offspring as well as dams and had immunosuppressive effects in the postnatal model of toxicity as well as cytotoxicity to hepatic cells lines.

Biological responses and toxicopathic effects elicited in Solea senegalensis juveniles on exposure to contaminated sediments under laboratory conditions

Whole-sediment toxicity assays contribute to elucidating the intricate association between the presence of contaminants in sediments and their toxicopathic effects in benthic fish. In the present study, Solea senegalensis juveniles were exposed under laboratory conditions to contaminated whole-sediments for 7 and 28 days. Sediments were obtained from a low to moderately polluted estuary, a highly polluted harbour and from the mixture of both field-collected sediments. Biometry data were recorded. Liver, brain, gills, and gonads were dissected out and processed to determine markers of oxidative stress, neurotoxicity and lysosomal biomarkers, and histopathology. Analyses of sediment granulometry and chemical profiles indicated different degrees of toxicity and suggested a distinct release of pollutants from each sediment in relation with their physicochemical properties. Interestingly, biological responses were in agreement with contaminant levels reported in source sediments. The most distinct toxicopathic effects were detected upon exposure to the harbour's sediment and particularly on day 28. Overall, enhanced hepatic glutathione-S-transferase activity and lysosomal enlargement were detected in all experimental groups, demonstrating a toxic effect from all sediments whilst catalase inhibition, lysosomal membrane destabilisation, changes in lysosomal content and liver histopathology were most pronounced in soles exposed to the harbour's sediment. The Integrative Biomarker Response index (IBR/n) evidenced that exposure to the three sediments caused an impact of diverse magnitude in sole health (IBR/nHarbour > IBR/nMixture > IBR/nEstuary). The magnitude of biological responses essentially depended on the presence of contaminants in source sediments, which seemed to be altered by the conditions imposed by whole-sediment toxicity assays.

Bicyclol Attenuates Acute Liver Injury by Activating Autophagy, Anti-Oxidative and Anti-Inflammatory Capabilities in Mice.

Bicyclol, a novel synthetic antihepatitis drug, has been shown to protect against liver injury via various pharmacological activities. The purpose of the current study was to further investigate the protective effect of bicyclol against carbon tetrachloride (CCl4)-induced acute liver injury (ALI) and its underlying molecular mechanism, particularly autophagic machinery, anti-oxidative, and anti-inflammatory potentials. Our results found that treatment with bicyclol significantly reduced CCl4-induced hepatotoxicity by alleviating histopathological liver changes, decreasing the alanine transaminase levels, promoting autophagic flux, attenuating the expression of inflammatory cytokines, and modulating oxidative markers. Furthermore, bicyclol efficiently induced the conversion of LC3 and enhanced the liver expressions of ATG7 and Beclin-1. Meanwhile, bicyclol induced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and p62. These protective effects may be mediated by activation of AMP-activated protein kinase and inhibition of mTOR or MAPK signaling pathways. Taken together, our study firstly suggests that bicyclol has protective potential against CCl4-induced hepatotoxicity, which might be closely associated with induction of autophagy, concomitant anti-oxidative stress, and anti-inflammatory response.

Poikilocytosis and tissue damage as negative impacts of tramadol on juvenile of Tilapia (Oreochromis niloticus)

Pharmaceuticals residue was detected in the water bodies as a consequence of the incomplete treatment. Recently, the side impacts of that residue on aquatic creatures have received a considerable attention. However, there is insufficient information about the effect of the most consumed narcotic drug (tramadol) on fish as an aquatic model. Thus, this study aims at investigating the poikilocytosis and tissue damage in Oreochromis niloticus after the exposure to 100 and 200 mg/L of tramadol hydrochloride. Three groups of fish were used; one as a control group, and the other two groups were exposed to 100 mg/L and 200 mg/L of tramadol hydrochloride respectively for 25 days. Exposure to tramadol caused a significant increase in the percentage of poikilocytosis compared to the control group. Poikilocytosis included tear-drop cell, spindle-shaped cell, sickle cell, schistocyte, blebbed cell, acanthocyte, eccentric nucleus, amoebocyte, dividing cell, and crenated cell. Moreover, liver tissue in fish exposed to tramadol showed degeneration and vacuolization of hepatocytes and atrophy of pancreatic acini as signs of histopathological alterations. Histopathological changes of brain showed severe gliosis, dark neurons, and vacuolization in fish exposed to tramadol compared to control fish. Gills tissue showed erosion, epithelial lifting, and secondary lamellae shrinking in fish exposed to tramadol compared to control fish. In conclusion, tramadol induced histopathological changes in liver, brain, and gills of Oreochromis niloticus as well as poikilocytosis were indicated clearly. Therefore, tramadol leakage to waters should be avoided to preserve aquatic creatures.

Trigonella stellata reduced the deleterious effects of diabetes mellitus through alleviation of oxidative stress, antioxidant- and drug-metabolizing enzymes activities

Ethnopharmacological relevanceGenus Trigonella has a history of folkloric medicinal uses in China, Japan, Egypt and India. There are a variety of therapeutic actions of Trigonella including hypocholesterolemia, hypoglycemia, antibacterial, antiviral, anti-inflammatory activities, antioxidants and appetite stimulant. Aim of the studyThe prevalence of diabetes mellitus is increasing annually. The present study aims at investigating the protective effects of Trigonella stellata against the adverse effects of diabetes mellitus through investigation of the changes in phase I & II drug-metabolizing enzyme activities, protein expression of cytochrome P450 isoenzymes [CYP2E1 & 3A4], oxidative stress, antioxidant enzymes as well as histopathology of both liver and kidney tissues. MethodsGC-MS and MALDI-TOF were used to analyze the main constituents of the aqueous and the ethanolic extract of Trigonella stellata. Western immunoblotting technique used to show the protein expression of CYP450 isozymes in different groups. Spectrophotometric- and fluorophotometric techniques were also used for assessment of different hepatic integrity enzymes. Histopathological techniques used to illustrate the changes in the tissues of both livers and kidneys after different treatments. ResultsTrigonelline was found to be the main constituent of both aqueous and ethanolic extract of Trigonella stellata. Administration of the aqueous and/or the ethanolic extracts of Trigonella stellata to the diabetic rats was found to decrease the blood glucose level, the biochemical markers of both liver (transaminases activities, Lactate dehydrogenase, gamma-glutamyl transferase) and the renal functions (urea, creatinine and bilirubin) which were increased in diabetic-treated rats relative to their normal levels. Diabetes mellitus potentially induced the oxidative stress, and also activities of dimethylnitrosamine N-demethylase I, cytochrome c-reductase, ethoxyresourfin O-deethylase, and the total hepatic content of cytochrome P450. On the other hand, the activity of catalase [CAT], superoxide dismutase [SOD], glutathione S-transferase [GST], glutathione reductase [GR], glutathione peroxidase [GPx] and levels of reduced glutathione [GSH] were potentially inhibited in diabetic rats compared to the control rats. However, treatments of diabetic rats with either aqueous and/or ethanolic extracts of Trigonella stellata restored such changes caused by diabetes almost nearly to their normal levels compared to the control group. Supporting the activity of dimethyl nitrosamine N-demethylase I activity, the protein expression of CYP2E1 was also induced in diabetic rats. However, the aqueous extract of Trigonella stellata was more effective than ethanolic extract in restoring the changes in the protein expression of CYP2E. On the other hand, the protein expression of CYP3A4 was markedly decreased in diabetic rats, and this decrease was partially restored to its normal level after treatment of diabetic rats with aqueous and/or ethanolic extracts. In addition, Trigonella stellata extracts alleviated the histopathological changes in livers and kidneys caused by diabetes mellitus. ConclusionIt is concluded that diabetes mellitus induced changes in oxidative stress, phase I & II drug-metabolizing enzymes, and antioxidant enzymes activities, whereas both extracts of Trigonella stellata alleviated such changes. Alterations in cytochrome P450 system should be considered when therapeutic drugs are administered to diabetic patients since most of xenobiotic are mainly metabolized by this system.