Liver Tissue Concentrations Research Articles

Swertiamarin Attenuates Experimental Rat Hepatic Fibrosis by Suppressing Angiotensin II-Angiotensin Type 1 Receptor-Extracellular Signal-Regulated Kinase Signaling.

The rennin-angiotensin system (RAS) is crucial in hepatic fibrosis development, and therapies targeting this system may be a promising treatment for hepatic fibrosis. In this study, we investigated the effects of swertiamarin (Swe), an ethanol extract of Gentiana manshurica Kitag, on hepatic fibrosis and its underlying mechanisms through regulating RAS. Primary rat hepatic stellate cells (HSCs) were isolated and treated with angiotensin II (Ang II) with or without Swe and losartan. The proliferation and activation of HSCs were measured. Rat hepatic fibrosis was induced by intraperitoneal dimethylnitrosamine (DMN) injection for 4 weeks. Rats were treated with Swe or losartan from the third week until the end of the experiment. Hydroxyproline content in liver tissue was assayed with Jamall's method, and liver collagen deposition was visualized using Sirius red staining. RAS components were analyzed by Western blot, immunofluorescent staining, and real-time reverse-transcription polymerase chain reaction. The results showed that Swe significantly inhibited Ang II-induced HSC proliferation and activation. Swe also significantly suppressed DMN-induced α-smooth muscle actin production in rat livers and improved liver function. Swe partially inhibited Ang II-induced angiotensin type 1 receptor (AT1R) up-regulation and suppressed Ang II-induced extracellular signal-regulated kinase (ERK) and c-jun phosphorylation in HSCs. In the DMN-treated rats, Swe treatment significantly inhibited the plasma Ang II levels. DMN-induced AT1R up-regulation, and phosphorylation of ERK and c-jun in rat liver were also inhibited by Swe. In conclusion, Swe may attenuate hepatic fibrosis through inhibiting HSC activation by regulating the RAS.

Disposition and Pharmacokinetics of a GalNAc3-Conjugated Antisense Oligonucleotide Targeting Human Lipoprotein (a) in Monkeys.

Triantennary N-acetyl galactosamine (GalNAc3)-conjugated antisense oligonucleotides (ASOs) have greatly improved potency due to receptor-mediated uptake into hepatocyte. The disposition and pharmacokinetics of ISIS 681257, a GalNAc3-conjugated ASO, were studied in monkeys. Following subcutaneous (SC) injection, ISIS 681257 was rapidly absorbed into the systemic circulation, with peak plasma levels observed within hours after dosing. After reaching Cmax, plasma concentrations rapidly declined in a multiexponential manner and were characterized by a dominant initial rapid distribution phase in which drug transferred to tissues from circulation, followed by a much slower terminal elimination phase (half-life of 4 weeks). Intact ISIS 681257 is the major full-length oligonucleotide species in plasma (≥70%). In tissues, the conjugated-GalNAc sugar moiety was rapidly metabolized, leaving the fully unconjugated form as the only full-length oligonucleotide detected at 48 h after dosing. Unconjugated ISIS 681257 cleared slowly from tissues with a half-life of 4 weeks. ISIS 681257 was highly bound to plasma proteins (>97% bound), which limited its urinary excretion. Disposition of ISIS 681257 in plasma and liver appeared nonlinear over the 1-40 mg/kg dose range studied. The plasma and liver tissue concentration data were well described by a population based mixed-effects modeling approach with Michaelis-Menten uptake from plasma to liver. Safety data from the study and the good exposure, as well as the extended half-life of the unconjugated ASO in the liver, support further development and less frequent dosing in Phase I clinical study.

Spatial and temporal analysis of the risks posed by polychlorinated biphenyl and metal contaminants in dab (Limanda limanda) collected from waters around England and Wales

The metals cadmium, mercury and lead, and the ICES7 CB levels were analysed in the common dab Limanda limanda to investigate whether concentrations of these determinants are at levels above established OSPAR assessment criteria around England and Wales. The results indicate that CB118 is above the OSPAR derived EAC at 22 out of 29 sampled stations, with 15 showing significant reductions. Cadmium is increasing significantly at six stations with two sites in the North Sea breaching corresponding OSPAR EAC. Mean results for all other PCBs and metals stayed below the EAC thresholds, with Hg concentrations even falling below BAC levels at South Eddystone located in the western English Channel. This study shows that PCBs banned over 20years ago are still found at concentrations in fish liver tissues which may pose a health risk to both the individual fish and their predators.

Ameliorative effect of vitamin C against hepatotoxicity induced by emamectin benzoate in rats.

In the present study, we aimed to assess the potential protective effect of ascorbic acid (AA) against emamectin benzoate (EMB)-induced hepatotoxicity. For this purpose, biochemical, histopathological and analytical investigations were performed. Male Wistar rats were distributed into three groups, that is, a control group, an EMB group given 10 mg EMB/kg body weight (BW) by gavage and an EMB + AA group given 10 mg EMB/kg BW and vitamin C intraperitoneally (200 mg/kg). The duration of the treatment was 28 days and the duration of the study was 42 days. There was a statistically significant increase of all hepatic biomarkers, that is, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase activities, and glycemia, in EMB-treated group when compared with the control group. Light microscopic observations revealed variable signs of hepatotoxicity in the EMB group, which were represented by alteration of normal hepatic architecture, inflammatory cell infiltration, hepatocellular steatosis and foci of necrosis at 28 and 42 days post-treatment. However, co-treatment with vitamin C reduced EMB-related liver toxicity and diminished the abnormal biochemical and architectural damage. Emamectin B1a and B1b residues were detectable in all plasma samples of treated rats at 14, 21 and 28 days of treatment. The drug liver tissue concentration was significantly lower in EMB + AA group compared with EMB group at 28 and 42 days. In conclusion, the findings of the present study clearly indicate a significant protective action of vitamin C against EMB hepatotoxicity.

α-Tocopherol Attenuates the Triglyceride- and Cholesterol-Lowering Effects of Rice Bran Tocotrienol in Rats Fed a Western Diet.

Previous studies demonstrated the ability of tocotrienol (T3) to lower levels of lipids, including cholesterol (Cho) and triglycerides (TG). Although α-tocopherol (α-Toc) reportedly inhibits the hypocholesterolemic effect of T3, there is no information about whether α-Toc influences the TG-lowering effect of T3 in vivo. In this study, we investigated the influence of α-Toc on the antihyperlipidemic effects (Cho- and TG-lowering) of rice bran tocotrienols (RBT3) in F344 rats fed a western diet. α-Toc attenuated both the Cho- and TG-lowering effects of RBT3 in vivo, whereas α-Toc alone exhibited no hypolipidemic effects. RBT3-induced Cpt-1a and Cyp7a1 gene expression was reduced by α-Toc. Furthermore, coadministration of α-Toc decreased liver and adipose tissue concentrations of tocotrienols in F344 rats. These results indicate that α-Toc has almost no antihyperlipidemic effect in vivo, but abrogates the antihyperlipidemic effect of RBT3 by reducing tissue concentrations of tocotrienols and regulating expression of genes involved in lipid metabolism. Understanding the underlying mechanism of the beneficial effects of T3 on lipid metabolism and the interaction with α-Toc will be important for developing T3-based therapeutics.

In vivo Magnetic Resonance Microscopy and Hypothermic Anaesthesia of a Disease Model in Medaka.

In medical and pharmacological research, various human disease models in small fish, such as medaka (Oryzias latipes), have been created. To investigate these disease models noninvasively, magnetic resonance imaging (MRI) is suitable because these small fish are no longer transparent as adults. However, their small body size requires a high spatial resolution, and a water pool should be avoided to maximize the strength of MRI. We developed in vivo magnetic resonance microscopy (MR microscopy) without a water pool by combining hypothermic anaesthesia and a 14.1 T MR microscope. Using in vivo MR microscopy, we noninvasively evaluated the hepatic steatosis level of a non-alcoholic fatty liver disease model in medaka and followed the individual disease progression. The steatosis level was quantified by the MRI-estimated proton density fat-fraction (MRI-PDFF), which estimates the triglyceride fat concentration in liver tissue and is recognized as an imaging biomarker. The MRI-PDFF results agreed with a histological analysis. Moreover, we optimized the hypothermic anaesthesia procedure to obtain a recovery proportion of 1 in the experiment involving MR microscopy. Recovered medaka could not be distinguished from naïve medaka after the experiment. Therefore, the in vivo MR microscopy will expand the possibilities of a human disease model in fish.

Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice

Sidt2 is a newly discovered lysosomal membrane protein that is closely related to glucose metabolism. In the present study, we found that Sidt2 is also closely related to lipid metabolism. Gradual increases in serum triglyceride (TG) and free fatty acid, as well as elevated aspartate transaminase and alanine transaminase levels were observed in Sidt2−/− mice fed a normal diet from the age of 3 months, suggesting the presence of lipid metabolism disorders and impaired liver function in these mice. In the liver slices of 6-month-old Sidt2−/− mice, there were obvious fat degeneration and inflammatory changes. Almost all of the liver cells demonstrated different levels of lipid droplet accumulation and cell swelling, and some of the cells demonstrated balloon-like changes. Infiltration of inflammatory cells was observed in the portal area and hepatic lobule. Electron microscopy showed that macrophages tended to be attached to the endothelial cells, and a large number of lipid droplets were present in the liver cells. Oil red O staining showed that there were significantly increased number of deep straining particles in the liver cells of Sidt2−/− mice, and the TG content in liver tissue was also significantly increased. Detection of key genes and proteins related to fat synthesis showed that mRNA and protein levels of the SREBP1c in the liver of Sidt2−/− mice were significantly elevated, and the downstream genes acetyl-CoA carboxylase, fatty acid synthase, and mitochondrial glycerol 3-phosphate acyltransferase were significantly upregulated. In addition, there was severe endoplasmic reticulum stress (ERS) in the liver of Sidt2−/− mice, which had significantly increased levels of markers specific for unfolded protein response activation, Grp78 and CHOP, as well as significant elevation of downstream p-PERK, p-eIF2a, p-IRE1a, along with ER damage. These results suggest that Sidt2−/− mice had spontaneous nonalcoholic fatty liver disease (NAFLD) accompanied by ERS. In summary, as a lysosomal membrane protein, Sidt2 plays an important role in the pathogenesis of NAFLD, and ERS may mediate the occurrence and development of this disease in Sdit2 deficiency mice.

Heavy metal concentrations in gill and liver tissues of Rutilus kutum and Chelon aurata in the coast of Babolsar, southern Caspian Sea

Heavy metal accumulation in the aquatic ecosystems is a main concern which threats human health. In this study two commercial fish species, Rutilus kutum and Chelon aurata were selected for assessing heavy metal (Cd, Pb, Zn) concentrations in gill and liver tissues at Babolsar’s coast, the southern Caspian Sea, Iran. Babolsar is one of the important fishery stations in the southern Caspian Sea. The results showed that liver tissue of C. aurata significantly accumulated higher concentration of Cd, Pb and Zn compared to that of R. kutum , but these results were not significant for gill tissue. Liver tissue accumulated higher concentration of Cd and Pb compared to gill tissue in C. aurata , but these results were not significant for R. kutum . It is concluded that the liver tissue of C. aurata has higher potential to accumulate heavy metal pollution compared to liver tissue of R. kutum

Synergistic protective effect of Scutellariae Radix with Phellodendri Chinensis Cortex on Dioscoreae Bulibferae Rhizoma liver toxicity in rats

Dioscoreae Bulibferae Rhizoma (RDB) is commonly used in clinical Chinese medicine. It has been used in many kinds of traditional Chinese medicine (TCM), but the toxicity of RDB, easily leads to hepatotoxicity. The objective of the present study is to investigate the synergistic protective effect of Scutellariae Radix (SR) with Phellodendri Chinensis Cortex (PCC) on RDB caused liver toxicity in rats. SD female rats were adopted to establish the hepatotoxicity models by RDB (9 g•kg⁻¹, ig) once daily for 28 consecutive days. After 28 days, liver histological changes were observed, and the activity of transaminase and antioxidant enzymes was evaluated. Morphological and biochemical indicators evaluation showed that, Dioscoreae Bulibferae Rhizoma-induced hepatotoxicity models were successful, and the liver cells were dissolved and swelling with fatty degeneration； inflammatory cells were present in gaps; local punctiformed or lamellar hydropic degeneration was found in liver tissues, with partial necrosis. Indexes of liver function (ALT, AST and ALP) were significantly increased (P<0.05 or P<0.01). The combination of SR and PCC has protective effect on RDB-induced hepatotoxicity in rats. SR+PCC exerted the strongest protective effects against RDB-induced hepatotoxicity. SR, PCC, and SB+CP were observed to exhibit hepatoprotective effect as demonstrated by significant decrease in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) (P<0.05 or P<0.01), and MAD level in liver tissue (P<0.001), significant increase in GSH content in liver tissue (P<0.001), and significant improvement in his to pathologic changes of liver tissues in rats. SR, PCC and their combinations could achieve liver protection effect by reducing ALT, ALP and AST level in serum, increasing GSH level and anti-oxidantability of liver tissues, and reducing hepatic tissue cells injury.

Biotransformation of inorganic arsenic in a marine herbivorous fish Siganus fuscescens after dietborne exposure

Arsenic (As) is well known to be biodiminished along marine food chains. The marine herbivorous fish at a lower trophic level are expected to accumulate more As. However, little is known about how marine herbivorous fish biotransform the potential high As bioaccumulation. Therefore, the present study quantified the biotransformation of two inorganic As species (As(III) and As(V)) in a marine herbivorous fish Siganus fuscescens following dietborne exposure. The fish were fed on As contaminated artificial diets at nominal concentrations of 400 and 1500 μg As(III) or As(V) g−1 (dry weight) for 21 d and 42 d. After exposure, As concentrations in intestine, liver, and muscle tissues of rabbitfish increased significantly and were proportional to the inorganic As exposure concentrations. The present study demonstrated that both inorganic As(III) and As(V) in the dietborne phases were able to be biotransformed to the less toxic arsenobetaine (AsB) (63.3–91.3% in liver; 79.0%–95.2% in muscle). The processes of As biotransformation in rabbitfish could include oxidation of As(III) to As(V), reduction of As(V) to As(III), methylation to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and subsequent conversion to AsB. These results also demonstrated that AsB synthesis processes were diverse facing different inorganic As species in different tissues. In summary, the present study elucidated that marine herbivorous fish had high ability to biotransform inorganic As to the organic forms (mainly AsB), resulting in high As bioaccumulation. Therefore, marine herbivorous fish could detoxify inorganic As in the natural environment.

Negative Impact of Hypoxia on Tryptophan 2,3-Dioxygenase Function.

Tryptophan is an essential amino acid for hosts and pathogens. The liver enzyme tryptophan 2,3-dioxygenase (TDO) provokes, by its ability to degrade tryptophan to N-formylkynurenine, the precursor of the immune-relevant kynurenines, direct and indirect antimicrobial and immunoregulatory states. Up to now these TDO-mediated broad-spectrum effector functions have never been observed under hypoxia in vitro, although physiologic oxygen concentrations in liver tissue are low, especially in case of infection. Here we analysed recombinant expressed human TDO and ex vivo murine TDO functions under different oxygen conditions and show that TDO-induced restrictions of clinically relevant pathogens (bacteria, parasites) and of T cell proliferation are abrogated under hypoxic conditions. We pinpointed the loss of TDO efficiency to the reduction of TDO activity, since cell survival and TDO protein levels were unaffected. In conclusion, the potent antimicrobial as well as immunoregulatory effects of TDO were substantially impaired under hypoxic conditions that pathophysiologically occur in vivo. This might be detrimental for the appropriate host immune response towards relevant pathogens.

Modulatory Role of Selenium Nanoparticles and Grape Seed Extract Mixture on Oxidative Stress Biomarkers in Diabetic Irradiated Rats.

Abstract: Introduction: Diabetes is a metabolic disorder of several etiologies, many oral anti-hyperglycemic agents such as sulfonylurea, biguanides are obtainable, but these agents have side effects, thus there is need of a new natural anti-hyperglycemic agent. Methods: The present study was performed to evaluate the protective role of selenium nanoparticles-grape seed extract (SeNPs-GSE) mixture in ameliorating the changes in the oxidative stress biomarkers induced by gamma radiation in diabetic rats. Experimental model of diabetic irradiated rats was induced by single intrapertoneal injection of streptozotocin (STZ 45 mg/kg) followed by γ-radiation exposure (4 Gy). Forty eight rats were randomly classified into 6 experimental groups: normal, diabetic, irradiated, diabetic irradiated, diabetic treated with either SeNPs-GSE mixtureor glimepiride(1 mg) for (14) days followed by γ-radiation. Results: Results of the present study indicated that rats exposed to γ-radiation and, or STZ significantly increase serum glucose& liver MDA levels. This increase was accompanied by a decrease in the levels of serum insulin, total antioxidant (TAC), liver enzyme activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), as well as liver tissue contents of vitamin C (Vit.C) and vitamin E (Vit.E). Diabetic rats treated with (SeNPs–GSE) mixture or glimepiride before γ-radiation exert a significant improvement in all tested biochemical parameters. Conclusion: The present study showed that a mixture of (SeNPs -GSE) possesses antioxidant and anti-diabetic activities by decreasing oxidative stress biomarkers as well as blood glucose level tested in this study. The tested combination (SeNPs–GSE) mixture is more or less equally active as that of the standard tested anti-diabetic drug glimepiride. Ke ywords: Diabetes mellitus, Selenium nanoparticles, Grape seed extract, oxidative stress, Vitamin C, E.

Citrus flavonoid, naringenin, increases locomotor activity and reduces diacylglycerol accumulation in skeletal muscle of obese ovariectomized mice.

Estrogen deficiency has been associated with central obesity, muscle loss and metabolic syndrome in postmenopausal women. This study assessed naringenin accumulation in tissues and investigated the hypothesis that naringenin reverses diet-induced metabolic disturbances in obese ovariectomized mice. In study 1, we measured naringenin concentrations in plasma, liver, perigonadal and subcutaneous adipose tissues, and muscle of ovariectomized C57BL/6J female mice after 11 weeks of naringenin supplementation. Naringenin accumulated 5-12 times more in mice fed a 3% naringenin diet than in mice fed a 1% naringenin diet. In study 2, ovariectomized mice were fed a high-fat diet (60 kcal% fat) for 11 weeks and half of the mice were then supplemented with 3% naringenin for another 11 weeks. Dietary naringenin suppressed weight gain, lowered hyperglycemia and decreased intra-abdominal adiposity evaluated by magnetic resonance imaging. Naringenin-fed mice exhibited elevated locomotor activity monitored by infrared beam breaks, maintained muscle mass and reduced muscle diacylglycerol content. Real-time PCR analysis in muscle revealed decreased mRNA level for genes involved in de novo lipogenesis, lipolysis and triglyceride synthesis/storage. Long-term 3% naringenin supplementation resulted in significant naringenin accumulation in plasma and tissues, associated with attenuated metabolic dysregulation and muscle loss in obese ovariectomized mice.

Dietary toxicity of soluble and insoluble molybdenum to northern bobwhite quail (Colinus virginianus).

Limited data are available on the effects of molybdenum (Mo) on avian wildlife, which impairs evaluation of ecological exposure and risk. While Mo is an essential trace nutrient in birds, little is known of its toxicity to birds exposed to molybdenum disulfide (MoS2), the predominant form found in molybdenite ore. The chemical form and bioavailability of Mo is important in determining its toxicity. Avian toxicity tests typically involve a soluble form of Mo, such as sodium molybdate dihydrate (SMD, Na2MoO4·2H2O); however MoS2 is generally insoluble, with low bioaccessibility under most environmental conditions. The current study monitored survival and general health (body weight and food consumption) of 9-day old northern bobwhite exposed to soluble Mo (SMD) and ore-related Mo (MoS2) in their diet for 30 days. Toxicity and bioavailability (e.g. tissue distribution) of the two Mo forms were compared. Histopathology evaluations and serum, kidney, liver, and bone tissue sample analyses were conducted. Copper, a nutrient integrally associated with Mo toxicity, was also measured in the diet and tissue. No treatment-related mortality occurred and no treatment-related lesions were recorded for either Mo form. Tissue analyses detected increased Mo concentrations in serum, kidney, liver, and bone tissues following exposure to SMD, with decreasing concentrations following a post-exposure period. For the soluble form, a No-Observed-Adverse-Effect Concentration (NOAEC) of 1200 mg Mo as SMD/kg feed (134 mg SMD/kg body weight/day) was identified based on body weight and food consumption. No adverse effects were observed in birds exposed to MoS2 at the maximum dose of 5000 mg MoS2/kg feed (545 mg MoS2/kg body weight/day). These results show that effects associated with MoS2, the more environmentally prevalent and less bioavailable Mo form, are much less than those observed for SMD. These data should support more realistic representations of exposure and risks to avian receptors from environmental Mo.

Safety Evaluation, in Vitro and in Vivo Antioxidant Activity of the Flavonoid-Rich Extract from Maydis stigma

This study aimed to assess the acute toxicity and safety of flavonoid-rich extract from Maydis stigma (FMS) in mice. The in vitro antioxidant activity of FMS was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethyl-benzthiazoline-6-sulphonate) (ABTS) scavenging assays. Furthermore, the in vivo antioxidant of FMS against ethanol-induced oxidative damage in mice was determined by analysis of the serum total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA) content, liver tissue glutathione (GSH) content, and protein carbonyl (PC) content in liver tissue. The oral administration of FMS at doses of 30 g/kg did not cause death in mice, and there were no significant biologically adverse effects in mice. These results indicated that the median lethal dose (LD50) is higher than this dose. The IC50 values of FMS for the DPPH and ABTS scavenging activity were 50.73 and 0.23 mg/mL, respectively. Meanwhile, FMS could significantly enhance T-SOD activity, reduce MDA content in the serum, increase GSH content, and decrease PC content in the liver tissue at the tested doses (25, 50, 100, 200 mg/kg·day). These results indicate that FMS can be generally regarded as safe and used potentially as a bioactive source of natural antioxidants.

The biochemical changes of ultrasonic waves on protein metabolism

The biochemical changes in liver marker enzymes and protein metabolism after repeated exposure todiagnostic ultrasonic waves in rabbits. Thirty-five male rabbits were used for the study; animals wereclassified to five equal groups. Group I (control group) not exposed to ultrasound (control group) whileother groups (II, III, IV and V) were exposed to diagnostic ultrasound (5.5 MHz) 2 times per week fordifferent time (15, 30, 45 and 60min) for 5 weeks, respectively. Our results revealed that a highlysignificant increase of serum liver marker enzymes (ALT, AST, GGT, Alp activities, total protein),protein concentration in liver tissue, and changes in protein electrophoresis were observed after ten timesof ultrasound exposure. Also a significant increase of serum urea and uric acid concentrations wereobserved in groups III, IV and V. with changes in electrophoretic pattern of liver protein electrophoresisafter five and ten times of exposure to ultrasound. Our results showed that, ultrasound exposure hadpositive anabolic effect on protein metabolism when used for short period as 15 min. However, it had anegative effect on protein metabolism when used for long durations more than 15 min of exposure

Ameliorative effect of novel nanocomposite: basic curcumin nanoparticles modified with basic nano black seeds (nigella sativa) and calcium ascorbate on metabolic changes in experimentally induced tumor in female mice

The ameliorative effect and antitumor activity of basic curcumin nanoparticles modified with basic nanoblack seeds (nigella sativa) and calcium ascorbate were evaluated. eighty female mice were divided into4 equal groups of 20 mice each. Group 1: non – tumor bearing mice (NTBM). Group 2: tumor bearingmice(TBM). Group 3: NTBM + nanocomposite (4.750gm / kg. b.wt /day ) , orally for 6 weeks . Group4: TBM + nanocomposite (4.750gm / kg. b.wt/day ), orally for 6 weeks . Blood samples for serumseparation and liver tissues specimens were collected from all animal groups three times after 2, 4 and6 weeks from the onset of treatment. All serum was directly used for determination of ALT and ASTactivities and urea and creatinine concentrations. Moreover, antioxidants enzymes (catalase, GPX,SOD), GSH and MDA were detected in liver tissue. The obtained results showed significant decreasein catalase, GPX and SOD activities and GSH concentration in liver tissue of tumor bearing mice.Meanwhile, liver MDA, serum transferases(ALT and AST) activities, urea and creatinine concentrationswere significantly increased in tumor bearing mice . TBM treated with nanocomposite improve theadverse biochemical changes induced by tumor. So, this nanocomposite has potential benefits in cancertreatment

The Ameliorative Effect of Propolis Extract (bee glue) Against Oxidative Damage Induced by Methotrexate in Rats

Methotrexate (MTX) is an anti-folate used to treat cancer and some inflammatory diseases. The efficacy of MTX is often limited by its severe toxicity. Propolis is one of the most significant bee products that has an important role in balancing antioxidant systems and has an anti-peroxidant effect on several tissues. The present study was conducted to investigate the ameliorative effect of propolis against the methotrexate induced oxidative damage on blood, liver and kidney in rats. A total of one hundred and twenty male Wistar albino rats of mean body weights 90 ± 5 g were divided into 5 groups. Rats were administered their respective doses of propolis and/or MTX for 3, 6 and 9 weeks intervals. Control groups (G1 and G2), propolis group (G3), methotrexate group (G4) and methotrexate and propolis co-administered group (G5).The results showed that the MTX significant reduced hemoglobin concentration, hematocrit %, MCHC value, RBCs, WBCs and platelets count and significantly increased MCV and lymphocytes %. Moreover, it caused a significant increase in MDA level and significant decrease in GSH concentration in liver tissue as compared to normal control group (G1) in a time dependent manner. MTX administration also caused significant increase in serum AST, ALT and ALP activities in a time dependent manner, but a significant increase in total bilirubin only in 9 weeks as compared to normal control (G1). On the other hand, MTX impaired kidney function as reflected by a significant increase in serum urea and creatinine levels and decrease in serum uric acid level as compared to normal control group. Results suggest that administration of propolis extract (G5) help reduce the deleterious effects due to MTX injection in a time dependent manner, whereas, administration for 9 weeks offers better alleviation over 6 or 3 weeks. Data showed that long term administration of MTX for 9 weeks produce maximum damage over 6 or 3 weeks. Propolis extract administration also recovered the structural and functional integrity of the hepatic cells.

Otolith Chemistry of Common Sculpins (Myoxocephalus scorpius) in a Mining Polluted Greenlandic Fiord (Black Angel Lead-Zinc Mine, West Greenland)

Sculpins are widely used as key species for monitoring heavy metal pollution near arctic mine sites. Typically, metal concentrations in liver and muscle tissue have been used as a proxy for metal exposure but such analyses lack temporal information of uptake and accumulation. Otoliths (ear bones) are considered metabolically stable and can potentially contain a complete record of the fish’s metal exposure history. To investigate the otolith chemistry of sculpins and the potential of these as records of metal exposure, common sculpins (Myoxocephalus scorpius) were collected at five sites near a former Pb–Zn mine in West Greenland. Otoliths were analyzed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for 12 elements of which Mg, Mn, Sr, Ba, and Pb were detected. The highest Pb concentrations were found within the otoliths from the most Pb-polluted sites near the mine (up to 0.6 ppm), and decreasing concentrations were observed in a gradient away from the mine. Notably, Pb and Sr variations were closely correlated and showed an annual oscillatory pattern with peaks consistently found in the winter zones. It is not clear to what the extent high winter-time accumulation of Pb in the otoliths is due to high winter-time exposure of Pb through diet or water and/or to physiological processes such as growth in the sculpins. The study indicates that LA-ICP-MS analyses of sculpin otoliths have the potential to become a valuable method for assessing time-resolved metal loading near mine sites but also that more studies are required to investigate the links between metal sources, pathways, and processes affecting otolith metal deposition.

Influence of formula versus sow milk feeding on trace element status and expression of zinc-related genes in the jejunum, liver and pancreas of neonatal piglets

Increasing litter sizes in modern swine production have raised an urgent need for artificial rearing strategies and formula feeding. The current experiment was conducted to study the influence of formula trace element concentration according to recommendations for weaned piglets on the mRNA concentration of zinc (Zn)-related genes in the jejunum, liver and pancreas of neonatal piglets. Eight artificially reared piglets were fed a cow-milk-based formula (Group FO) containing 100 mg Zn/kg dry matter. Eight of their sow-reared littermates (Group SM) were used as control. After 14 d, all 16 piglets were killed and the jejunum, liver and pancreas were evaluated for Zn, copper, manganese (Mn) and iron (Fe) concentration and mRNA concentration of metal and Zn-specific transporters, metallothioneins (MT) and interleukin 6 (IL-6). In Group FO the Zn concentration in liver tissue was increased (p < 0.05). Furthermore, Fe and Mn concentrations in liver and jejunal tissue were higher (p < 0.05) in Group FO, whereas neither Zn transporters nor MT in jejunal and pancreatic tissue showed differences between both groups. In the liver of Group FO, MT mRNA concentration was higher (p < 0.05), whereas Zn transporter protein 1 and divalent metal-ion transporter 1 (DMT1) mRNA concentration was lower (p < 0.05). Besides Zn-induced expression of transporters and MT, the significantly increased IL-6 expression in Group FO suggests the involvement of cytokine-mediated Mn and Fe sequestration in the liver and jejunum. The results revealed that dietary trace element concentration used in the study likely exceeded the requirements of neonatal pigs as reflected by homeostatic counter-regulation in different organs.