Despite all the studies performed to date, therapy choices for liver injuries are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries ...remains a challenge. Quercetin (QR) and ellagic acid (EA) had potent antioxidant and anti-inflammatory activities. The current study aimed at evaluating the potential hepatoprotective influence of QR and EA against thioacetamide (TAA)-induced liver toxicity in rats and the underlying mechanism using silymarin as a reference drug. Fifty mature male rats were orally treated daily with EA and QR in separate groups for 45 consecutive days, and then were injected with TAA twice with 24 h intervals in the last 2 days of the experiment. Administration of TAA resulted in marked elevation of liver indices, alteration in oxidative stress parameters, and significant elevation in expression level of fibrosis-related genes (MMP9 and MMP2). Administration of QR and EA significantly attenuated the hepatic toxicity through reduction of liver biomarkers, improving the redox status of the tissue, as well as hampering the expression level of fibrosis-related genes. In this study, QR and EA were proved to attenuate the hepatotoxicity through their antioxidant, metal-chelating capacity, and anti-inflammatory effects.
•A Fe3O4@SiO2-GO@MIPs was fabricated for recognition of four flavonoids.•LC–MS/MS based on MIPs was developed for determination of four flavonoids in Rhododendrons.•The method exhibited good ...performance to extract four flavonoids in real samples.
Herein, a novel magnetic molecularly imprinted polymer doped with reticular graphene oxide (Fe3O4@SiO2-GO@MIPs) was synthesized for the selective recognition and extraction of 4 flavonoids (farrerol, taxifolin, kaempferol, and hyperin) from Rhododendrons species. The Fe3O4@SiO2-GO@MIPs with lamellar membranes showed outstanding adsorption capacity. The 3D cavities complementary to the “shape” of farrerol were “imprinted” on the polymer framework after removal of farrerol template. Competitive binding assays showed that the polymer has a higher selectivity for farrerol compared with other analogues and references. The Fe3O4@SiO2-GO@MIPs as solid-phase extraction adsorbents combined with liquid chromatography-tandem quadrupole mass spectrometry (LC–MS/MS) was used for selective determination of four flavonoids from Rhododendrons samples. The limits of detection (LOD) were 0.07, 0.08, 0.06, and 0.08 μg L−1 for farrerol, taxifolin, kaempferol, and hyperin, respectively. These results suggest that the prepared Fe3O4@SiO2-GO@MIPs have the potential applicability to extract, purify, and enrich flavonoids from herbs, supplements, and other natural products.
Hepatic encephalopathy depicts the cluster of neurological alterations that occur during acute or chronic hepatic injury. Hyperammonemia, inflammatory injury, and oxidative stress are the main ...predisposing factors for the direct and indirect changes in cerebral metabolism causing encephalopathy. The aim of this study was to evaluate the possible synergistic effect between aminoguanidine (AG; 100 mg/kg, p.o.) and
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-carnosine (CAR; 200 mg/kg, p.o.) on hepatic encephalopathy that was induced by thioacetamide (TAA; 100 mg/kg, i.p.) administered three times weekly for six weeks. Behavioral changes, biochemical parameters, histopathological analysis, and immunohistochemical and ultrastructural studies were conducted 24 h after the last treatment. Combining AG with CAR improved TAA-induced locomotor impairment and motor incoordination evidenced by reduced locomotor activity and decline in motor skill performance, as well as ameliorated cognitive deficits. Moreover, both drugs restored the levels of serum hepatic enzymes and serum and brain levels of ammonia. In addition, the combination significantly modulated hepatic and brain oxidative stress biomarkers, inflammatory cytokines, and cleaved caspase-3 expression. Furthermore, they succeeded in activating nuclear erythroid 2-related factor 2 (Nrf2) expression and heme oxygenase-1 (HO-1) activity and ameliorating markers of hepatic encephalopathy, including hepatic necrosis and brain astrocyte swelling. This study shows that combining AG with CAR exerted a new intervention for hepatic and brain damage in hepatic encephalopathy due to their complementary antioxidant, anti-inflammatory effects and hypoammonemic effects via Nrf2/HO-1 activation and NO inhibition.
Liver fibrosis is a chronic wound-healing response to liver injury of various origins and represents a major health problem.
The current study endeavored to investigate the repressing effect of ...fisetin on hepatic fibrosis induced by thioacetamide (TAA) in rats.
Rats were injected with TAA (200 mg/kg) intraperitoneally twice per week for 6 weeks to induce liver fibrosis. Fisetin (50 and 100 mg/kg/day) or silymarin (50 mg/kg/day) were given orally on a daily basis along with TAA. Liver function parameters, oxidative stress, inflammatory and fibrogenic biomarkers as well as wnt3a, β-catenin, glycogen synthase kinase 3 (GSK-3β) and cyclin D1 were estimated. Histoapthological and immunohistochemical examinations were performed.
Fisetin restored normal liver functions, increased reduced glutathione (GSH) level and decreased malondialdehyde (MDA), as well as inflammatory biomarkers including; tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Additionally, it lessened transforming growth factor β1 (TGF-β1), collagen I and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels as well as elevated matrix metalloproteinase-9 (MMP-9) hepatic content. Furthermore, fisetin significantly suppressed wnt3a gene expression associated with decreased β-catenin and increased GSK-3β levels. Moreover, fisetin decreased the progress of histologic hepatic fibroplasia and diminished hepatic expression of α-SMA and cyclin D1.
Fisetin curbed liver fibrosis and exhibited superior activity over silymarin through inhibition of hepatic stellate cells (HSCs) activation and proliferation via suppressing the Wnt/β-catenin pathway, modulating MMP-9 and TIMP-1, and inhibiting multiple profibrogenic factors, besides its antioxidant and anti-inflammatory effects. Therefore, fisetin is a promising therapeutic candidate for hepatic fibrosis.
The present study aimed to evaluate the effect of trigonelline (TRG) on the hepatic complications associated with high-fat high-fructose (HFHF) diet-induced insulin resistance (IR) in rats. IR was ...induced by giving a saturated fat diet and 10% fructose in drinking water to rats for 8 weeks. Insulin-resistant rats were orally treated with TRG (50 and 100 mg/kg), sitagliptin (SIT; 5 mg/kg), or a combination of TRG (50 mg/kg) and SIT (5 mg/kg) for 14 days. Liver homogenates were used for assessment of hepatic lipids, oxidative stress biomarkers, and inflammatory cytokines. Histopathological and DNA cytometry examinations were carried out for hepatic and pancreatic tissues. Hepatic tissues were examined using Fourier-transform infrared spectroscopy for assessment of any molecular changes. Results of the present study revealed that oral treatment of insulin-resistant rats with TRG or TRG in combination with SIT significantly decreased homeostatic model assessment of IR, hepatic lipids, oxidative stress biomarkers, and the inflammatory cytokines. TRG or TRG in combination with SIT ameliorated the histopathological, DNA cytometry, and molecular alterations induced by a HFHF diet. Finally, it can be concluded that TRG has beneficial effects on the hepatic complications associated with IR due to its hypoglycemic effect and antioxidant potential.
•A method for determination of bupivacaine hydrochloride and isoflupredone acetate has been developed and validated.•Residues were determined in porcine muscle, beef, milk, egg, shrimp, flatfish, and ...eel samples using LC–MS/MS.•Solution of 0.1% of acetic acid in acetonitrile and n-hexane was used as a simple sample preparation.•Monitoring was performed following the developed method and none of the samples were tested positive.
In this study, a simple analytical approach has been developed and validated for the determination of bupivacaine hydrochloride and isoflupredone acetate residues in porcine muscle, beef, milk, egg, shrimp, flatfish, and eel using liquid chromatography-tandem mass spectrometry (LC–MS/MS). A 0.1% solution of acetic acid in acetonitrile combined with n-hexane was used for deproteinization and defatting of all tested matrices and the target drugs were well separated on a Waters Xbridge™ C18 analytical column using a mobile phase consisting of 0.1% acetic acid (A) and 0.1% solution of acetic acid in methanol (B). The linearity estimated from six-point matrix-matched calibrations was good, with coefficients of determination ≥0.9873. The limits of quantification (LOQs) for bupivacaine hydrochloride and isoflupredone acetate were 1 and 2ngg−1, respectively. Recovery percentages in the ranges of 72.51–112.39% (bupivacaine hydrochloride) and 72.58–114.56% (isoflupredone acetate) were obtained from three different fortification concentrations with relative standard deviations (RSDs) of <15.14%. All samples for the experimental work and method application were collected from the local markets in Seoul, Republic of Korea, and none of them tested positive for the target drugs. In conclusion, a simple method using a 0.1% solution of acetic acid in acetonitrile and n-hexane followed by LC–MS/MS could effectively extract bupivacaine hydrochloride and isoflupredone acetate from porcine muscle, beef, milk, egg, shrimp, flatfish, and eel samples.
This research assessed the impact of flunixin meglumine (FM) co-administration on the elimination and milk residual properties of oxytetracycline (OTC) in dairy goats. OTC was administered via single ...intravenous (i/v) and intramuscular (i/m) injections at a dose of 10 mg/kg body mass (b.m.). Serum, urine, milk and ruminal juice were analysed using high-performance liquid chromatography (HPLC). The OTC serum concentrations were higher than the MIC for 12 hours against most susceptible pathogens in both groups. The half-lives of the distribution (T.sub.1/2alpha) and elimination (T.sub.1/2beta of OTC were 0.24 and 5.79 hours, respectively. The total body clearance was significantly increased in the FM coadministered groups. Following i/m injection, the absorption half-life (T.sub.1/2ab) with the maximum absorption time (T.sub.max) revealed a rapid absorption rate. Furthermore, the systemic bioavailability (F%) after i/m was 107.2%, indicating complete absorption from the muscular tissues. The bounded fraction of OTC with serum proteins was 18.73%. FM significantly decreases OTC concentration in milk and ruminal juice. OTC is eliminated primarily through the kidneys and to a lesser extent via milk and ruminal juice in dairy goats. Milk obtained from OTC treated goats may not be safe for human consumption two days post administration. Concomitantly, the use of FM with OTC may necessitate the surveillance and optimization of OTC dosage. Key words: oxytetracycline; flunixin meglumine; elimination; milk; residues; goats
To examine the effect of osteopontin inhibition by tranilast on liver fibrosis, four groups of rats were used throughout this study. Group I (Control group): rats received the solvent. Liver fibrosis ...was induced in Groups II, III, and IV by thioacetamide (TAA; 200mg/kg, ip) twice weekly for 6 weeks. Group II served as (TAA group). Groups III and IV (Treatment groups): rats were given tranilast for 6 weeks after TAA discontinuation. Liver osteopontin (OPN), transforming growth factor-β (TGF-β1), tumor necrosis factor alpha (TNF-α), alpha-smooth muscle actin (ɑ-SMA)), reduced glutathione (GSH), superoxide dismutase (SOD) and lipid peroxidation (MDA) were measured. Additionally, expression of α-smooth muscle actin (SMA) and caspase (Cas)-3 were assigned immunohistochemically. Treatment with tranilast prevented the development of hepatic fibrosis and the activation of stellate cells, and down-regulated the expression of genes for osteopontin and osteopontin-target molecules, including TGF-β and TNF-α and α-SMA.Tranilast significantly decreased MDA and increased levels of GSH, and SOD. Our findings suggest that targeting osteopontin with tranilast represents a new mode of therapy for liver fibrosis.
The aim of the present study was to investigate the potential antioxidant and Hepatoprotective activities of tranilast against TAA-induced liver fibrosis in rats. Methods: Liver fibrosis was induced ...in rats by intra peritoneal injection of TAA (200 mg/kg) for 6 weeks. Tranilast was administered orally at a dose of 150 and 300mg/kg for 6 weeks before induction of liver fibrosis. Results: Injection of TAA induced hepatic fibrosis that was manifested by a significant increase in the activities of aminotransferases and total bilirubin with a significant decrease in total protein and albumin in serum. Liver homogenate of TAA rats had the lower content of reduced glutathione (GSH) and superoxide dismutase (SOD) with increased levels of the hepatic malondialdehyde. Histological data presented marked damage in liver sections of TAA rats. Oral dosing of tranilast for 6 weeks before induction of liver fibrosis reversed these altered parameters near to normal values. These results suggest that tranilast could afford significant protection and antioxidant effect in prevention of liver fibrosis.
Istražen je utjecaj fluniksina-meglumina (FM) na uklanjanje i rezidualna svojstva oksitetraciklina (OTC) u mlijeku mliječnih pasmina koza. OTC je dan jednokratno intravenski i intramuskularno u dozi ...od 10 mg/kg tjelesne mase. Serum, urin, mlijeko i buražni sok analizirani su tekućinskom kromatografijom visoke učinkovitosti (HPLC). Koncentracije OTC u serumu bile su tijekom 12 sati više od najmanje inhibitorne koncentracije za najosjetljivije patogene u objema skupinama. Vrijeme polurazgradnje OTC-a (T1/2α) bilo je 0,24 sata, a vrijeme uklanjanja (T1/2β) 5,79 sati. Vrijeme potpunog uklanjanja OTC-a statistički znakovito je poraslo u skupinama kojima je istodobno dan i fluniksin-meglumin. Nakon intramuskularne injekcije poluvijek apsorpcije (T1/2ab) s maksimalnim vremenom apsorpcije (Tmax) pokazao je veću brzinu apsorpcije. Osim toga sistemska bioraspoloživost (F %) nakon intramuskularne primjene bila je 107,2 % što upućuje na potpunu apsorpciju iz mišićnih tkiva. Dio OTC-a vezan na serumske proteine iznosio je 18,73 %. Fluniksin-meglumin statistički znakovito je smanjio koncentracije OTC-a u mlijeku i buražnom soku. OTC je uklonjen ponajprije putem bubrega i, u manjoj mjeri, mlijekom i buražnim sokom u mliječnih pasmina koza. Mlijeko dobiveno od koza kojima je davan OTC nije prikladno za upotrebu u ljudi do dva dana nakon primjene. Istodobna primjena FM-a s OTC-om može zahtijevati praćenje i optimizaciju OTC doze.
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