Plasma Aspartate Aminotransferase Levels Research Articles

Preventive Effect of Ganoderma lucidum on Paracetamol-induced Acute Hepatotoxicity in Rats

The effect of Ganoderma lucidum in paracetamol-induced acute hepatotoxicity was investigated on Wistar rats in the present study. Hepatotoxicity was induced by oral administration of paracetamol (500 mg/kg of body weight) for 7 consecutive days. The extent of liver damage was studied by assessing biochemical parameters comprising of plasma aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), total bilirubin (TB) and total plasma total protein (TP). Oral administration of paracetamol significantly increased the plasma levels of AST, ALT, ALP and LDH with concomitant decrease of TP. The feeding of G. lucidum (1% powder with basal food) significantly reversed the plasma levels of ALT, AST, ALP, LDH, and TP nearly to those of the normal rats. Thus, the results of the present demonstrate that the G. lucidum has significant hepatoprotective activity against paracetamol induced acute hepatotoxicity in rats.

Endoscopic Duodenal–Jejunal Bypass Liner Rapidly Improves Plasma Parameters of Nonalcoholic Fatty Liver Disease

Bariatric surgery reduces nonalcoholic fatty liver disease (NAFLD). We investigated the effects of duodenal-jejunal bypass liner (DJBL), nonsurgical bariatric device, on plasma parameters of NAFLD. Seventeen obese subjects with type 2 diabetes received the DJBL for 24 weeks. Before, during, and after DJBL implantation, we determined plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltransferase (γ-GT), albumin, caspase-cleaved cytokeratin-18 (CK-18), and liver fatty acid-binding protein (L-FABP). At baseline, subjects had increased levels of AST (35 ± 4 IU/L), ALT (54 ± 5 IU/L), and γ-GT (66 ± 14 IU/L), compared with healthy individuals; subjects' mean concentrations of caspase-cleaved CK-18 and L-FABP were 214.4 ± 35.6 U/L and 29.3 ± 2.6 ng/mL, respectively. Three months after implantation of DJBL, all NAFLD-related parameters had decreased from baseline (AST, 28 ± 3 IU/L; ALT, 32 ± 2 IU/L; γ-GT, 44 ±7 IU/L; caspase-cleaved CK-18, 140.6 ± 16.3U/L; and L-FABP, 18.2 ± 1.5 ng/mL; all P < .05). After 6 months, levels of ALT and γ-GT had further decreased (ALT, 28 ± 2 IU/L and γ-GT, 35 ± 5 IU/L), whereas levels of AST, caspase-cleaved CK-18, and L-FABP had stabilized (P= not significant). Six months after DJBLs were removed, levels of ALT (37 ± 3 IU/L), γ-GT (42 ± 5 IU/L), and caspase-cleaved CK-18 (124.5 ± 12.5U/L) were still reduced (P < .05), whereas AST and L-FABP had returned to near baseline levels (P= not significant). Therefore, in obese subjects, DJBL reduces plasma parameters of NAFLD. ClinicalTrials.gov, Number: NCT00985114.

Development of a pulmonary peptide delivery system using porous nanoparticle-aggregate particles for systemic application

As a non-invasive administration route, pulmonary peptide delivery for systemic application has shown great promise. However, many barriers exist that prevent effective peptide delivery. The use of porous nanoparticle-aggregate particles (PNAPs) is an excellent option because of their proper aerodynamic size and maximal deposition. However, in most cases, the spray drying heating process for PNAPs has been challenging in regard to maintaining peptide stability and activity. To overcome these issues, we developed a spray freeze-drying method for PNAP preparation. To solve the low entrapment efficiency problem of nanostructured lipid carriers, we used hydrophobic ion pair complexes to increase the lipophilicity of the peptide, thus increasing entrapment efficiency and drug loading. Here, we used a model peptide, octreotide acetate, for PNAP preparation, which has a high entrapment efficiency (>95%) and proper aerodynamic size (~3 μm). In addition, after intrapulmonary administration, we evaluated the pharmacokinetics and pharmacodynamics in a rat preventive hepatic ischemia-reperfusion injury model. Our in vivo data showed significantly increased area under the curve and improved plasma aspartate aminotransferase levels for our PNAP intrapulmonary delivery system vs. the clinically used octreotide acetate delivery via subcutaneous injection. Together, PNAPs may have great potential for carrying peptide drugs for pulmonary delivery.

Protective effects of different dietary proportion of fish oil on hepatic injury in chronic ethanol‐fed rats

Excess consumption of alcohol is known to cause liver damage. The present study was to investigate the effects of different proportions of fish oil on hepatic aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and oxidative stress in ethanol‐fed rats. Male Wistar rats were divided into six groups (n=5/group) and fed with either the control diet or the alcohol diet, in which the fat composition of both diets was adjusted with 25% or 45% fish oil substitution for olive oil. The groups were C (control), 25%CF (control with 25% fish oil), 45%CF (control with 45% fish oil), E (ethanol), 25%EF (ethanol with 25% fish oil), and 45%EF (ethanol with 45% fish oil). Rats were sacrificed after 8 weeks of the treatments. Results showed that plasma levels of AST, ALT activities, 8‐isoprostaglandinF2α, triglyceride and total cholesterol were significantly decreased and hepatic GSH/GSSG ratio was significantly increased in the 25%EF and 45%EF groups than those in the E group (p&lt;0.05). In addition, the pathologic scores for microvesicular fatty change, degeneration and necrosis were significantly decreased in 25% EF and 45% EF groups as compared with that in the E group (p&lt;0.05). The results suggested that fish oil substitution could prevent ethanol‐induced liver damage. Supported by NSC100–2320‐B‐038–023‐MY3.

Astaxanthin supplementation lowers plasma triglyceride concentrations in diet‐induced obese C57BL/6J mice

Elevated plasma triglyceride (TG) and cholesterol concentrations are risk factors for cardiovascular diseases. We previously reported that astaxanthin (ASTX), a xanthophyll carotenoid, lowers plasma total cholesterol and TG concentrations in apolipoprotein E knockout mice. To investigate if ASTX exerts hypolipidemic effects in the diet‐induced obesity (DIO) mice and if so, to determine an effective supplementation level, male C57BL/6J mice were fed a high fat (HF) control diet (60% energy from fat) or a HF diet supplemented with 0.003%, 0.01% or 0.03% ASTX by weight for 12 wk. Only mice fed 0.03% ASTX showed a significant reduction in plasma TG levels, suggesting this level of supplementation is necessary for ASTX to have a TG‐lowering effect. Compared with control, plasma high density lipoprotein cholesterol (HDLc) levels were significantly higher in 0.03% ASTX‐fed mice without a difference in plasma non‐HDLc levels. The ASTX supplementation also decreased plasma aspartate aminotransferase levels, suggesting it protects against high fat‐induced tissue damages. In conclusion, 0.03% ASTX in diet decreased plasma TG and increased HDLc in DIO mice and therefore, it is potentially beneficial for lowering CVD risk.Grant Funding Source: USDA AFRI 2012–67018‐19290

5-lipoxygenase deficiency reduces acetaminophen-induced hepatotoxicity and lethality.

5-Lipoxygenase (5-LO) converts arachidonic acid into leukotrienes (LTs) and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP)-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO−/−) mice and background wild type mice were challenged with APAP (0.3–6 g/kg) or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO−/− mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1β, TNF-α, IFN-γ, and IL-10), superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate) assay were prevented in 5-LO−/− mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage.

Effects of vitamin C and E supplementation on oxidative stress and liver toxicity in rats fed a low-fat ethanol diet

We compared the preventive capacity of high intakes of vitamin C (VC) and vitamin E (VE) on oxidative stress and liver toxicity in rats fed a low-fat ethanol diet. Thirty-two Wistar rats received the low fat (10% of total calories) Lieber-DeCarli liquid diet as follows: either ethanol alone (Alc group, 36% of total calories) or ethanol in combination with VC (Alc + VC group, 40 mg VC/100 g body weight) or VE (Alc + VE group, 0.8 mg VE/100 g body weight). Control rats were pair-fed a liquid diet with the Alc group. Ethanol administration induced a modest increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), conjugated dienes (CD), and triglycerides but decreased total radical-trapping antioxidant potential (TRAP) in plasma. VE supplementation to alcohol-fed rats restored the plasma levels of AST, CD, and TRAP to control levels. However, VC supplementation did not significantly influence plasma ALT, AST, or CD. In addition, a significant increase in plasma aminothiols such as homocysteine and cysteine was observed in the Alc group, but cysteinylglycine and glutathione (GSH) did not change by ethanol feeding. Supplementing alcohol-fed rats with VC increased plasma GSH and hepatic S-adenosylmethionine, but plasma levels of aminothiols, except GSH, were not influenced by either VC or VE supplementation in ethanol-fed rats. These results indicate that a low-fat ethanol diet induces oxidative stress and consequent liver toxicity similar to a high-fat ethanol diet and that VE supplementation has a protective effect on ethanol-induced oxidative stress and liver toxicity.

Effect of simvastatin in hepatic ischemia and reperfusion in rats

Purpose: Liver injury induced by ischemia and reperfusion is frequently observed in the immediate postoperative period in liver transplantation and partial hepatectomy, when the liver is subjected to a period of partial or total ischemia at various times. The present study aimed to evaluate the effect of simvastatin in preventing liver ischemia-reperfusion injury in rats, using the biodistribution of radiopharmaceuticals, biochemical, immunological and histological analysis. Methods: Eighteen Wistar rats were randomly divided into three equal groups of six each. Group sham; Group IR (isquemia of left and medium hepatic lobes for 45 min; reperfusion for 24 hs); and IR simvastatin group. Animals from IR simvastatin group were treated with simvastatin microemulsion at a dose of 10mg/kg v.o. (gavage) once daily for 5 days before ischemia and reperfusion (IR). Results: Both the right and the left hepatic lobe had higher uptake of fitate-99mTc04 radioactivity in group IR simvastatin than in group IR (p&lt;0.05). The plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactic dehydrogenase (LDH) were measured at the end of each experiment. Simvastatin pretreatment led to a profound decrease in plasma enzyme levels compared with IR rats (p≤0.001). Histopathological examination revealed necrotic areas predominantly in the perivenular zone, cytoplasm vacuolization and sinusoidal congestion in an IR group rats. Simvastatin pretreatment strongly protected livers from these changes. Conclusion: In summary, our study provides the evidence that pretreatment with simvastatin protected rat livers from ischemia/reperfusion injury in vivo. This protective effect was validated by a decrease of plasma liver enzymes and histopathological features of liver injury, as well as by biodistribution of fitate-Tc99m in liver tissue.

Prediction of preeclampsia: liver function tests during the first 20 gestational weeks

Objective: To examine whether plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) during the first 20 weeks of pregnancy can predict preeclampsia in the second half of pregnancy. Methods: The study population included 150,10 registered births. Receiver operating characteristic (ROC) curve analysis was used to describe the relationship between different values of AST and ALT during the first 20 weeks of pregnancy in the prediction of preeclampsia. Results: Using ROC curve analyses, elevated ALT levels were significantly associated with both mild preeclampsia (p < 0.001) and severe preeclampsia (p = 0.032). However, an ALT level of 50 IU/L had a sensitivity of only 3.3% (despite a specificity of 97%) in the prediction of severe preeclampsia. While no significant association was noted between AST levels and mild preeclampsia (p = 0.669), elevated levels of AST during this period were significantly associated with severe preeclampsia (p = 0.027). However, AST of 50I U/L had a sensitivity of only 2.0% (despite a specificity of 98%) in the prediction of severe preeclampsia. Conclusions: Higher levels of the liver enzymes AST and ALT during the first 20 weeks of pregnancy are associated with higher risk for the development of severe preeclampsia in the second half of the pregnancy. Nevertheless, there is no clinical cutoff value that can be practically used for the prediction of preeclampsia.

Clinical Equivalence of Proprietary and Generic Atorvastatin in Lipid Clinic Patients

BackgroundThe loss of patent protection for proprietary statins offers affordability advantages to payers, but some clinicians still question the efficacy of generic formulations in real-world clinical applications. MethodsIn this retrospective cohort study, we examined the effects of generic atorvastatin substitution on relevant biochemical parameters in 85 dyslipidemic patients who had been previously maintained on stable doses of proprietary atorvastatin from 2009 to 2011. For comparison, we studied 143 patients who were continuously prescribed stable doses of rosuvastatin, which was only available in its proprietary formulation over the same time period. ResultsWe found that substitution of generic for proprietary atorvastatin was not associated with significant changes in plasma levels of total or low-density lipoprotein cholesterol, or triglycerides, but was associated with a small but significant increase in high-density lipoprotein cholesterol. Plasma levels of aspartate aminotransferase and creatine kinase were also unchanged. Additionally, the changeover to generic atorvastatin was not associated with increased switching to another statin or more frequent changes in other lipid-lowering medications compared with the proprietary rosuvastatin group. ConclusionsSubstituting generic for proprietary atorvastatin in lipid clinic patients was not associated with significant changes in efficacy, adverse events, or patient management.

Evaluation of Hepatoprotective Activities of &lt;i&gt;Satureja punctata&lt;/i&gt; Benth Briq and &lt;i&gt;Solanecio angulatus&lt;/i&gt; Vahl Jeffrey in Ferric Nitrillotriacetate Induced Hepatotoxicity in Rats

Satureja punctata Benth. Briq (Lamiaceae) and Solanecio angulatus Vahl Jeffrey (Asteraceae) are among the plants widely used in Ethiopian traditional medicine for the treatment of liver diseases. The study aimed at evaluating the hepatoprotective activity of the crude extracts and solvent fractions of these medicinal plants. Hepatoprotective activity was evaluated by measuring levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AP) as well as by morphologic pathology and antioxidant assay against ferric nitrilotriacetate induced hepatotoxicity in rats. Crude aqueous extract of S. punctata at 250 and 500 mg/kg suppressed plasma levels of AST and ALT (p&lt;0.01), and AP (p&lt;0.01 and p&lt;0.001). S. angulatus at 400 mg/kg decreased AP (p&lt;0.05), whilst 200 mg/kg reduced AST and AP (P&lt;0.01), without affecting ALT. The methanol fraction of S. punctata (500 mg/kg) showed maximum hepatoprotective activity comparable to silymarin (p&lt;0.001, in all cases). Likewise, the chloroform fraction (250 mg/kg) reduced to a similar extent (p&lt;0.01 in all cases). The aqueous fraction (250 mg/kg) showed significant reduction in AST and ALT (p&lt;0.001) and AP (p&lt;0.05), but 500 mg/kg failed to affect levels of AP. The methanol fraction was able to return the normal hepatic architecture of hepatocytes and scavenge free radicals in 1,1-diphenylpicrylhydrazyl (DPPH) assay. S. punctata is endowed with hepatoprotective activity, probably mediated via its antioxidant activity. Thus, S. punctata can be taken as one candidate&#160; for development of hepatoprotective agents as it was also showed good safety profile.Keywords: Satureja punctata, Solanecio angulatus, hepatoprotective, ferric nitrilotriacetate, antioxidant

Hemoadsorption Reprograms Inflammation in Experimental Gram-negative Septic Peritonitis: Insights from In Vivo and In Silico Studies

Improper compartmentalization of the inflammatory response leads to systemic inflammation in sepsis. Hemoadsorption (HA) is an emerging approach to modulate sepsis-induced inflammation. We sought to define the effects of HA on inflammatory compartmentalization in Escherichia coli-induced fibrin peritonitis in rats. HA both reprograms and recompartmentalizes inflammation in sepsis. Sprague Dawley male rats were subjected to E. coli peritonitis and, after 24 h, were randomized to HA or sham treatment (sepsis alone). Venous blood samples collected at 0, 1, 3 and 6 h (that is, 24-30 h of total experimental sepsis), and peritoneal samples collected at 0 and 6 h, were assayed for 14 cytokines along with NO(2)(-/)NO(3)(-). Bacterial counts were assessed in the peritoneal fluid at 0 and 6 h. Plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, CXCL-1, and CCL2 were significantly reduced in HA versus sham. Principal component analysis (PCA) suggested that inflammation in sham was driven by IL-6 and TNF-α, whereas HA-associated inflammation was driven primarily by TNF-α, CXCL-1, IL-10 and CCL2. Whereas -peritoneal bacterial counts, plasma aspartate transaminase levels and peritoneal IL-5, IL-6, IL-18, interferon (IFN)-γ and NO(2)(-)/NO(3)(-) were significantly lower, both CXCL-1 and CCL2 as well as the peritoneal-to-plasma ratios of TNF-α, CXCL-1 and CCL2 were significantly higher in HA versus sham, suggesting that HA-induced inflammatory recompartmentalization leads to the different inflammatory drivers discerned in part by PCA. In conclusion, this study demonstrates the utility of combined in vivo/in silico methods and suggests that HA exerts differential effects on mediator gradients between local and systemic compartments that ultimately benefit the host.

Serotonin protects mouse liver from cholestatic injury by decreasing bile salt pool after bile duct ligation

Obstructive cholestasis induces liver injury, postoperative complications, and mortality after surgery. Adaptive control of cholestasis, including bile salt homeostasis, is necessary for recovery and survival. Peripheral serotonin is a cytoprotective neurotransmitter also associated with liver regeneration. The effect of serotonin on cholestatic liver injury is not known. Therefore, we tested whether serotonin affects the severity of cholestatic liver injury. We induced cholestasis by ligation of the bile duct (BDL) in either wild-type (WT) mice or mice lacking peripheral serotonin (Tph1(-/-) and immune thrombocytopenic [ITP] mice). Liver injury was assessed by the levels of plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) and tissue necrosis. Bile salt-regulating genes were measured by quantitative polymerase chain reaction and confirmed by western blotting and immunohistochemistry. Tph1(-/-) mice displayed higher levels of plasma AST, ALT, bile salts, and hepatic necrosis after 3 days of BDL than WT mice. Likewise, liver injury was disproportional in ITP mice. Moreover, severe cholestatic complications and mortality after prolonged BDL were increased in Tph1(-/-) mice. Despite the elevation in toxic bile salts, expression of genes involved in bile salt homeostasis and detoxification were not affected in Tph1(-/-) livers. In contrast, the bile salt reabsorption transporters Ostα and Ostβ were up-regulated in the kidneys of Tph1(-/-) mice, along with a decrease in urinary bile salt excretion. Serotonin reloading of Tph1(-/-) mice reversed this phenotype, resulting in a reduction of circulating bile salts and liver injury. We propose a physiological function of serotonin is to ameliorate liver injury and stabilize the bile salt pool through adaptation of renal transporters in cholestasis.

The effect of adding fish oil to parenteral nutrition on hepatic mononuclear cell function and survival after intraportal bacterial challenge in mice

Parenteral nutrition (PN) is indispensable for meeting caloric and substrate needs of patients who cannot receive adequate amounts of enteral nutrition; however, PN impairs hepatic immunity. We examined the effects of ω-3 and -6 polyunsaturated fatty acids, added individually to fat-free PN, on hepatic immunity in a murine model. We focused on serum liver enzymes, cytokine production, histopathology, and the outcomes after intraportal bacterial challenge. Male Institute of Cancer Research mice were randomized into 4 groups; ad libitum chow (CHOW), fat-free PN (FF-PN), PN + fish oil (FO-PN), or PN + safflower oil (SO-PN). After the mice had been fed for 5 days, hepatic mononuclear cells (MNCs) were isolated. The number of MNCs was counted and cytokine production (tumor necrosis factor [TNF]-α and interleukin [IL]-10) by hepatic MNCs in response to lipopolysaccharide (LPS) was measured. Blood samples were analyzed for hepatobiliary biochemical parameters. Moreover, 1.0 × 10(7) pseudomonas aeruginosa were delivered by intraportal injection. Survival and histology were examined. Hepatic MNC numbers were significantly less in the FO-PN and FF-PN than in the CHOW group, whereas the SO-PN group showed moderate recovery of hepatic MNC numbers. The CHOW, FO-PN, and SO-PN groups showed LPS dose-dependent increases in TNF-α levels. These increases were blunted in the FF-PN group. IL-10 levels were increased LPS dose-dependently in the CHOW and FO-PN groups, but no marked changes were observed with LPS stimulation in the SO-PN and FF-PN groups. Plasma levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were significantly greater in the FF-PN than in the FO- and SO-PN and CHOW groups. The FO-PN group showed significantly improved survival compared with the SO-PN and FF-PN groups, showing essentially no morphologic hepatic abnormalities. Addition of fish oil to PN was advantageous in terms of reversing PN-induced deterioration of hepatic immunity, as reflected by altered cytokine production. Fish oil administration was also useful for preventing PN-induced hepatobiliary dysfunction. These changes seem to result in better survival and to protect against severe tissue damage after intraportal bacterial challenge. This therapy may have the potential to ameliorate PN-induced impairment of host immunity and thereby decrease morbidity and mortality.

The toxic effects of nickel chloride on liver, erythropoiesis, and development in Wistar albino preimplanted rats can be reversed with selenium pretreatment

The exposure to nickel chloride (NiCl₂) can cause hematotoxicity and hepatotoxicity and canaffect development. The present study pertains to the protective effect of selenium (Se) against NiCl₂-induced toxicity in preimplanted Wistar albino rats. The subcutaneous (s.c.) administration of 25 or 50 mg/kg of NiCl₂ to Wistar albino rats on day 3 of gestation induced an immediate and significant decrease in maternal body weight and anemia 2 days after treatment. In addition, an increase in plasma aspartate aminotransferase (AST) was observed. These effects were maintained on day 20 of gestation. Moreover, a significant increase in plasma alanine aminotransferase (ALT) levels was observed with the administration of 25 mg/kg of NiCl₂. Conversely, administration of 50 mg/kg of NiCl₂ by s.c. injection increased erythropoiesis at day 20 of gestation and decreased platelets counts. In addition, administration of 100 mg/kg of NiCl₂ markedly reduced the maternal body weight and number of live fetuses and increased fetal loss, predominantly at the end of the experimental period. All dose levels of NiCl₂ caused an alteration in the hepatic histoarchitecture. When 0.3-mg/kg Se was injected s.c. with 100-mg/kg NiCl₂, the levels of plasma AST and ALT and the structure of the liver were restored. Administration of 20 mg/L/day of NiCl₂ in the drinking water significantly reduced the maternal body weight at day five of gestation as well as erythropoiesis during the exposure period. The present study suggests that Se can counteract the nocuous effect of nickel on the liver; however this antioxidant did not prevent alterations in development and erythropoiesis.

A critical life-supporting role for cystathionine γ-lyase in the absence of dietary cysteine supply

This study examined the important relationship between cystathionine γ-lyase (CSE) functionality and cysteine supply for normal growth and life span. Mice with a targeted deletion of the CSE gene (CSE-KO) were fed a cysteine-limited diet and their growth and survival patterns as well as levels of cysteine, homocysteine, glutathione, and hydrogen sulfide (H2S) were measured. CSE-KO mice fed a cysteine-limited diet exhibited growth retardation; decreased levels of cysteine, glutathione, and H2S; and increased plasma homocysteine level. However, histological examinations of liver did not reveal any abnormality and plasma levels of aspartate aminotransferase, alanine aminotransferase, and albumin were normal in these animals. No CSE-KO mice survived after 12weeks of feeding with the cysteine-limited diet. Supplementation of H2S to the CSE-KO mice failed to reverse the aforementioned abnormalities. On the other hand, supplementation of cysteine in the drinking water of the CSE-KO mice significantly increased plasma cysteine and glutathione levels. This eventually led to an increase in body weight and rescued the animals from death. In conclusion, CSE is critical for cysteine biosynthesis through the transsulfuration pathway and the combination of CSE deficiency and lack of dietary cysteine supply would threaten life sustainability.

Alteration in the Pharmacokinetics of Hemoglobin-Vesicles in a Rat Model of Chronic Liver Cirrhosis Is Associated with Kupffer Cell Phagocyte Activity

The hemoglobin-vesicle (HbV) is a cellular, hemoglobin-based oxygen carrier. Our previous pharmacokinetic studies demonstrated that the liver is strongly associated with the metabolism and excretion of HbV. The aim of this study was to evaluate the pharmacokinetics of HbV in a chronic cirrhosis rat (CCR) model induced by carbon tetrachloride (CCl(4) ) and explore whether liver functional parameters and Kupffer cell (KC) phagocyte activity are related to the pharmacokinetics of HbV. The CCRs were induced three times weekly by intraperitoneal administration of CCl(4) for 8 weeks and categorized as Child-Pugh grade B. To analyze the pharmacokinetics, the CCRs were given a single intravenous injection of (3) H-HbV (1400 mg of Hb/kg). The total clearance and hepatic distribution of HbV were negatively correlated with plasma aspartate aminotransferase (AST) levels (p = 0.007). In addition, the phagocyte index was negatively correlated with plasma AST levels (p = 0.047). The excretion of lipid components in feces was also negatively correlated with plasma AST levels (p = 0.049). In conclusion, alteration in the pharmacokinetics of HbV in CCRs can be attributed to a decrease in KC phagocyte activity and the extent of damage to parenchymal cells. This represents the first demonstration of the pharmacokinetics of a liposome preparation in chronic liverimpairment.

Haematological and biochemical values of the blood of pheasants (Phasianus colchicus) of different ages

This study was conducted to determine selected haematological and biochemical parameters of pheasants (Phasianus colchicus) bred in Konya city in Turkey. Forty-five healthy pheasants of different ages (1, 5, and 12 months old) were examined. In the blood samples taken from these animals, haematological and biochemical values were determined. Comparing the haematological and biochemical parameters among the age groups, red blood cell counts, haemoglobin amount, haematocrit values, lymphocyte percentage, and total protein and albumin levels increased with the advancement of age. However, glucose, length and width of erythrocyte, length and width of erythrocyte nucleus, and percentages of monocyte and basophile decreased with the advancement of age. Furthermore, the white blood cell counts of the chick and the adults, the plasma total cholesterol and triglyceride of the adults, and the plasma uric acid levels of the chicks were lower than those of the young pheasants. However, thrombocyte count of the chicks was higher than that of the young pheasants. The other parameters investigated, such as mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, the percentages of heterophils and eosinophils, and the plasma levels of aspartate aminotransferase, alanine aminotransferase, creatinine, and creatine kinase did not show significant differences related to age. Based on the results, it was concluded that some haematological and biochemical values were influenced by age differences of the pheasants and the data obtained in this study could be useful to establish some baseline values about haematological and biochemical parameters in pheasants.

Anti-obesity Effect of Phosphatidylinositol on Diet-Induced Obesity in Mice

The aim of this study is to investigate the biodistribution of phosphatidylinositol (PI) after oral administration and its anti-obesity effect. When a suspension of radiolabeled PI was orally administered to mice and the biodistribution was examined, PI radioactivity accumulated in the liver compared to myo-inositol radioactivity at 48 h or later after administration. Then, a PI suspension was orally administered to diet-induced obesity (DIO) mice every 4 days, and the anti-obesity effect of PI was examined. As a result, PI suppressed the body weight increase of DIO mice and significantly reduced the plasma levels of aspartate aminotransferase (AST) and cholesterol. Furthermore, PI regulated the expression of some genes in the liver involved in lipid synthesis and metabolism. The present study demonstrated that PI accumulated in the liver after oral administration and exerted its anti-obesity effect on DIO by regulating the expression of certain genes involved in lipid metabolism in the liver.

Stress‐induced multiple organ damage in rats is ameliorated by the antioxidant and anxiolytic effects of regular exercise

Our aim was to investigate the effects of moderate load, regular swimming exercise on stress-induced anxiety, and associated oxidative organ injury. Male Sprague-Dawley rats (n = 48) were either kept sedentary or submitted to swimming exercise for 8 weeks. Rats were then divided as non-stressed, acute stress, and chronic stress groups. After acute or chronic stress (electric foot shocks) applications, rats were placed on a holeboard and the exploratory behavior was recorded to assess the anxiety. Rats were decapitated after the stress application. Acute and chronic stress induction led to increased serum cortisol levels as compared to non-stressed groups. Plasma aspartate aminotransferase levels that were elevated in sedentary rats with both stress exposures were lower in trained rats. Malondialdehyde levels and myeloperoxidase activity were increased in the cardiac muscle, liver, stomach, and brain of the stressed rats with a concomitant reduction in the glutathione levels, while stress-induced changes in malondialdehyde, myeloperoxidase, and glutathione levels were reversed in the trained animals. Exercise, which led to increased malondialdehyde and reduced glutathione levels in the skeletal muscle of the non-stressed rats, also protected against stress-induced oxidative damage. Regular exercise with its anxiolytic and antioxidant effects ameliorates stress-induced oxidative organ damage by a neutrophil-dependent mechanism.