Aristolochic Acid I-Induced Hepatotoxicity in Tianfu Broilers Is Associated with Oxidative-Stress-Mediated Apoptosis and Mitochondrial Damage

Aristolochic acid (AA) is a component of traditional Chinese herbs and commonly used for farm animals in China. Over-exposure of AA has been proven to be associated with hepatotoxicity; however, the mechanism of action of AA-I-induced hepatotoxicity remains unknown. In the current study, a subchronic toxicity test was conducted to evaluate the mechanism of AA-induced hepatotoxicity in Tianfu broilers. According to the results, AA-I-induced hepatotoxicity in Tianfu broilers was evidenced by the elevation of liver weight, levels of serum glutamic oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT). Furthermore, hepatocyte swelling, vesicular degeneration and steatosis were observed. Additionally, AA-I elevated the production of reactive oxygen species (ROS) and induced oxidative stress, which further led to excessive apoptosis, characterized by mitochondrial depolarization, upregulation of Bax, and down-regulation of Bcl-2 expression. In conclusion, the mechanism of AA-I-induced hepatotoxicity was associated with oxidative-stress-mediated apoptosis and mitochondrial damage.

Evaluation of in-vitro antioxidant potential and in-vivo hepatoprotective activity of root extract of Quercus oblongata D. DON

Objective: The main potential target is attempt to investigated evaluation of in-vitro antioxidant potential and in-vivo hepatoprotective activity of root extract of Quercus oblongata D. DON belonging to family fagaceae. Material & Methods: The root of plant was extracted by different solvents like n-hexane (NHEQO), Chloroform (CEQO), Ethyl acetate (EAQO) Hydroethanolic (HEEQO) and Ethanol (EEQO). The antioxidant activity (AA) was determined by the possible four complementary test assay methods namely total phenolic content, total flavonoids content, Inhibition of 2,2 diphenyl -1 picrylhydrazyl (DPPH) radicals and ABTS (2-2’- azinobis) radical scavenging activity or quenching activity, in the hepatoprotective experimental animal albino wistar rats (120-180gm) were divided into 6 group, each group content 5, Group I: Received distilled water (5ml/kg. p.o) once daily, and served as normal control. Group II: Received paracetamol suspension (640 mg/kg suspended in 1% methyl cellulose; orally as toxin control. Group III: Received standard drug Silymarin (25 mg/kg. p.o.) + paracetamol suspension (640 mg/kg suspended in 1% methyl cellulose; orally once daily Group IV, V, VI administered HEECB at different doses300, 400, 500 mg/kg orally + paracetamol suspension (640 mg/kg suspended in 1% methyl cellulose; for 21 days. And collect blood from experimental animals by retrorbital puncture for estimation of biochemical parameters and other parameter also evaluate like physical histological changes in livers of rats. Results: Experimental finding reveal that Paracetamol produce significant change in physical (increase liver weight) biochemical (increase alkaline phosphate, serum glutamic oxalacetic transaminase, serum glutamic pyuruvic transaminase, total protein, total bilirubin, direct bilirubin and decrease the level of total protein and albumin) histological (damage to hepatocyte) and in liver parameters. Pretreatment with extract significantly minimization of physical, biochemical, histological and functional change induced by Paracetamol in liver. Conclusion: Experimental data and analysis of different parameter declare that hydroethanolic extract of Quercus oblongata could be a useful hepatoprotective agents and antioxidant potential. Keywords: Clematis buchananiana, paracetamol, hepatoprotective, alkaline phosphate, serum glutamic oxalacetic transaminase, serum glutamic pyuruvic transaminase.

Reduction of toxic effects of aflatoxin B1 by using baker yeast (Saccharomyces cerevisiae) in growing broiler chicks diets

This study was carried out to investigate the effects of adding baker yeast (BY), chlortetracycline (CTC) and both BY + CTC to a control diet containing 200 ng/g of aflatoxin B1 (C + AFB1) on performance, serum parameters and pathologyc alterations of broilers. A total 100 chicks (Ross PM 3) were divided into five groups in individual cages and each containing 20 animals. BY, a rich source of protein and vitamin B complex, was mixed into the diets at 2.0 %, CTC was mixed into the diet at 2.5 ng/g. Feed consumption, body weight and feed efficiency were recorded weekly. Serum parameters and pathologyc alterations were determined at the end of the study. Dead animals were recorded daily. Liver changes were clearly apparent in the C+AFB1and C+ AFB1+CTC most of the livers were enlarged, yellow and had pethecial hemorrhages. Canalicula cholestosis was absent in group C+AFB1 and C+ AFB1+CTC, but not others. When compared to the control (C) group, alkaline phosphatase (ALP), appear to be significantly increased in the C+AFB1 and C+CTC+ AFB1 groups. Serum glutamic oxalacetic transaminase (GOT)was increased in C+AFB1 birds. Serum alphaphetoprotein was not affected by the treatments. Feed consumption and body weight were significantly reduced in group AFB1. Birds receiving BY + AFB1, CTC + AFB1 and BY + CTC + AFB1 had a significantly higher body weight than group C+AFB1. Feed efficiency was better in group CTC + AFB1 than the others. The findings of this research suggest tha BY (2%) can partly counteract some of the toxic effects of AFB1.

Effects of Cadmium On Liver Function in Diabetic Rats

Hepato-toxicity of cadmium in alloxan induced diabetic rats has been studied by estimating a few enzymes viz serum glutamic oxalacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase and γ-glutamyltranspeptidase. Present results suggest that cadmium manifests difterent effects in normal and diabetic rats. Insulin therapy helps in restoring the liver function. It is suggested that an isozyme of cytochrome P450 that appears in diabetic rats might be responsible for altered toxicity of cadmium.

Safety and pharmacokinetics of CS-834, a new oral carbapenem antibiotic, in healthy volunteers.

CS-834, (+)-[pivaloyloxymethyl (4R,5S,6S)-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(R)-5-oxopyrroli din-3-yl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate], is an ester-type oral carbapenem prodrug, and an active metabolite is R-95867, which has antibacterial activity. CS-834 was administered orally to healthy male volunteers at single doses of 50, 100, 200, and 400 mg and at a multiple dose of 150 mg three times a day for 7 days to investigate its safety and pharmacokinetic profiles. Other studies were conducted to examine the effect of food intake on the bioavailability of CS-834 and also the effect of the coadministration of probenecid on the pharmacokinetics of CS-834. In the fasting state, the concentration of R-95867 in plasma reached maximum levels from 1.1 to 1.7 h after the oral administration of CS-834, followed by a monoexponential decrease. The maximum concentrations of R-95867 in serum (C[max]s) after the administration of CS-834 at doses of 50, 100, 200, and 400 mg were 0.51, 0.97, 1.59, and 2.51 microg/ml, respectively. The half-lives (t1/2s) were almost constant, approximately 0.7 h. The areas under the concentration-time curves (AUCs) were proportional to the doses, ranging from 50 to 400 mg x h/ml. The cumulative recoveries in urine were approximately 30 to 35% until 24 h after drug administration. The C(max), AUC, t1/2, and recovery in urine were not affected by food intake. Probenecid coadministration prolonged the t1/2, and it increased the C(max) and AUC for R-95867 by approximately 1.5- and 2.1-fold, respectively. The multiple-dose study showed no change in the pharmacokinetics from those for the single doses and no drug accumulation in the body. A mild transient soft stool was observed in one volunteer in the study with a single dose of 400 mg. In the multiple-dose study, mild transient soft stools were observed in six volunteers, one volunteer had mild transient diarrhea, and one volunteer had elevated serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase levels (1.4- and 2.8-fold compared with the upper limits of normal, respectively). There were no other abnormal findings for objective symptoms or laboratory findings, including blood pressure, heart rate, electrocardiogram, body temperature, hematology, blood chemistry, and urinalysis.

In vivo testing of a pulsatile implantable impeller pump as a left ventricular assist device used in calves

A pulsatile implantable impeller pump was tested as a left ventricular assist device in five calves. The experiments lasted for 4-11 days. Death or termination was mainly due to respiratory complications or bleeding, irrelevant to the pump itself. As indicators of haemolysis, thrombogenesis, renal and hepatic functions, free haemoglobin( FHb), haematocrit (Hct), platelet number (Plt), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), creatinine, serum glutamic oxalacetic transaminase (GOT) and total bilirubin were measured preoperatively, at the beginning of the pumping (pump on), six hours later and every day thereafter. The data indicated that the pump caused no severe blood damage or organ dysfunction. Thus, the feasibility of a pulsatile centrifugal pump was demonstrated. The pump with its driver weighs 110 g and is capable of delivering a blood flow up to 8 l/min against 100 mmHg mean pressure.

Preliminary Study of Alpha-Fetoprotein in Nonmalignant Liver Diseases. A Clinico-Biochemical Evaluation

This preliminary study was carried out to evaluate the behavior of AFP in 155 patients with benign diffuse liver diseases who underwent thorough clinical and laboratory evaluation. We found correlations between AFP and some clinical and biochemical parameters characteristic of liver diseases; serum glutamic oxalacetic transaminase (GOT) proved the most relevant (r = 0.27 p = 0.0004) and most reliable marker to predict AFP levels. 22.6% of the patients as a whole, 25.6% of the 86 cirrhotics and 18.8% of the 69 non-cirrhotics, had increased levels of AFP. Patients with active liver disease as measured by increased GOT, had higher AFP levels than patients with quiescent liver diseases (p = 0.0048), suggesting that cytolysis and/or regeneration plays a role in the increase in AFP. Elevation of the cutoff level was necessary to improve the specificity of AFP as a tumor marker. In our series, the cutoff of 9 ng/ml was exceeded by only 10% of the patients.