Increased Serum Enzyme Activity Research Articles

ACTIVITY OF LIVER FUNCTION ENZYME AND ANTIBACTERIAL SUSCEPTIBILITY OF ANNONA SENEGALENSIS LEAF EXTRACT

In ethnomedicine, various natural products have been implicated in the treatment of several diseases. Annona senegalensis has been identified as one of the plants that have the potential to cure ailments arising from microbial infections. This study however was carried out to investigate the liver function enzyme activity and in vitro antibacterial susceptibility of the 50% ethanol-methanol leaf extract of A. senegalensis. The effect of the administration of 100 mg/kg body weight of A. senegalensis on serum enzyme parameters and antibacterial susceptibility was investigated in albino rats. Thirty-three albino rats with average weights of 200 g were divided into two groups. Group 1 contained 30 rats and was treated with 20 mg/mL of A. senegalensis leaf extract while Group 2 contained three rats and served as the control. The treatment lasted for 20 consecutive days while the rats in Group 1 were daily administered with the leaf extract of A. senegalensis. Data were analyzed and presented using a descriptive analysis from Microsoft Excel 2016 version. The results obtained from administration of the leaf extract of A. senegalensis on serum enzymes parameters show a significant increase in serum enzyme activity when compared to the control. This indicates that the leaf extracts of A. senegalensis have significant effects on the serum enzymes parameters. The in vitro antibacterial susceptibility of the leaf extracts relative to the drugs (Ampicillin and Ciprofloxacin) revealed that the leaf extract of the plant holds much promise in antibacterial property when combined with antibiotics used in this study. This research revealed that there is high activity of alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase in the serum following the administration of 100 mg/kg body weight of 50% ethanol-methanol leaf extract of A. senegalensis. The antibacterial susceptibility test of the leaf extract carried out in vitro also revealed the plant antibacterial property. The combination of A. senegalensis leaf extract with antibiotic drugs, especially the one used in this study hold much promise in its efficacy as revealed in its synergistic interaction.

Effects of dietary Cetobacterium somerae on the intestinal health, immune parameters and resistance against Nocardia seriolae of largemouth bass, Micropterus salmoides

Largemouth bass (Micropterus salmoides), one of the most important freshwater commercial fish species has been widely cultivated in China. In recent years, the nocardiosis caused by Nocardia seriolae has greatly damaged the M. salmoides industry and there is no effective treatment at present. Currently, Cetobacterium somerae, the predominant bacteria in the gut of many freshwater fishes has been reported to be associated with fish health. However, whether the native C. somerae could protect the host from N. seriolae is unclear. In this study, M. salmoides were fed with three different diets, including control diet (CD), low C. somerae diet (106 CFU/g as LD) and high C. somerae diet (108 CFU/g as HD). After 8-week feeding, growth performance, gut health index, serum enzyme activities and the expression of inflammation-related genes were tested. Results showed that the LD and HD diets had no adverse effects on the growth performance. Moreover, dietary HD enhanced gut barrier and reduced intestinal ROS and ORP, as well as increased serum enzyme activities including ACP, AKP, SOD and LZM compared to the CD group. In addition, the HD diet significantly up-regulated the expression of TNF-α, IL8, IL-1β and IL15, while down-regulating the expression of TGF-β1 and IL10 in kidney. Moreover, the expression of antibacterial genes was significantly increased in HD group after being challenged by N. seriolae. And the fish fed HD diet exhibited higher survival rate (57.5%) than that in CD (37.5%) and LD groups (42.5%). To summarize, our study demonstrates that dietary HD can enhance gut health, improve immune response and strengthen pathogen resistance, suggesting that C. somerae is a potential probiotic for defending against N. seriolae infection in M. salmoides.

Epigallocatechin Gallate and Glutathione Attenuate Aflatoxin B1-Induced Acute Liver Injury in Ducklings via Mitochondria-Mediated Apoptosis and the Nrf2 Signalling Pathway.

Aflatoxin B1 (AFB1) exists widely in feed and food with severe hazards, posing a serious threat to human and animal health. Epigallocatechin gallate (EGCG) and glutathione (GSH) have been reported as having anti-oxidative and other functions. The present study aimed to investigate the detoxification effect of EGCG and GSH alone or in combination on AFB1 exposure in ducklings. Fifty one-day-old male ducklings were randomly assigned into five experimental groups (n = 10): 1. Control (CTR); 2. 0.3 mg/kg BW AFB1 (AFB1); 3. 0.3 mg/kg BW AFB1 + 100 mg/kg BW EGCG (AFB1 + EGCG); 4. 0.3 mg/kg BW AFB1 + 30 mg/kg BW GSH (AFB1 + GSH); 5. 0.3 mg/kg BW AFB1 + 100 mg/kg BW EGCG + 30 mg/kg BW GSH (AFB1 + EGCG + GSH). The experiment lasted for seven days. Compared with the CTR group, AFB1 reduced growth performance, total serum protein and albumin content, increased serum enzyme activity (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase), and caused pathological damage to the ducklings' livers. AFB1 exposure increased malondialdehyde content and decreased superoxide dismutase, total antioxidant capacity, catalase, glutathione peroxidase activities, and glutathione content in the liver. EGCG and GSH alone or in combination mitigated these adverse effects. Meanwhile, EGCG and GSH attenuate apoptosis of hepatocytes, and regulated AFB1-induced changes in the abundance of genes contained in the Keap1/Nrf2 signalling and apoptotic pathways. Collectively, these results suggest that EGCG and GSH alleviate the hepatocyte injury induced by AFB1 by inhibiting oxidative stress and attenuating excessive mitochondria-mediated apoptosis.

Toxic effects of calcein injection on juvenile silver carp Hypophthalmichthys molitrix

Calcein (CAL), as a simple and effective fluorescent marker, has been widely used in the labeling of fish and shellfish for the past few decades. In the present study, a series of CAL doses (including 0, 25, 100, and 200 mg/kg) were injected into juvenile Hypophthalmichthys molitrix, which were then fed with feed without CAL for 32 days, to explore the effects of CAL injection on the levels of antioxidant enzymes and lipid peroxidation in different tissues. The results showed that the mortality of juvenile silver carp increased significantly in the treatment group. The increased serum enzyme activities (glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, and alkaline phosphatase) were assumed to be due to CAL-induced hepatic damage, and the stress was mainly concentrated in the early stages after CAL injection (i.e., 0–4 d). Moreover, higher CAL doses (≥ 100 mg/kg) could lead to greater toxicity in juvenile silver carp and damage the gills and hepatopancreas, but the antioxidant systems in the gills and hepatopancreas were able to successfully eliminate the excess CAL-induced reactive oxygen species for >16 d after CAL injection. These results confirmed that CAL injection could induce a strong oxidative stress response in juvenile silver carp and that oxidative stress was closely correlated with the injection dose and time after injection. Therefore, when CAL is used for fluorescent labeling of juvenile silver carp by injection, the injection dose of CAL should be restricted to ≤25 mg/kg, and the injected juveniles should be reared for at least 16 d. However, compared to other application methods (e.g., direct immersion, feeding, and osmotic induction), injection might not be the recommended method for marking juvenile silver carp.

Early Diagnosis of Postpancreatectomy Acute Pancreatitis after Pancreaticoduodenectomy: A Study Using Biomarkers and Diffusion-Weighted Magnetic Resonance Imaging

Introduction: Early phases of postpancreatectomy acute pancreatitis (PPAP) are poorly characterized but might represent novel therapeutic opportunities. This study aims to investigate the radiologic, biochemical, and clinical spectrum associated with PPAP. Method: 65 patients undergoing pancreaticoduodenectomy prospectively collected. IVIM magnetic resonance imaging (MRI) at 1.5T scanner was performed on a postoperative day (POD) 3. Serum pancreatic amylase and lipase were assessed after surgery and daily until POD 5. PPAP was defined based on radiologic findings. Results: PPAP incidence was 9.2%. All patients with PPAP had a sustained increased serum enzyme activity persisting at least 48 hours (POH–postoperative serum hyper-amylasemia, -lipasemia) and lead to the worst postoperative outcome with (all p<0.05) high incidence of local (postoperative pancreatic fistula: 83%) and systemic morbidity (Clavien Dindo≥grade IIIb: 67%). Still, 21.5% and 24.6% of cases with no radiologic features of PPAP showed POH, without significant differences in median serum activity. Patients with POH-PPAP had significantly lower values of true diffusion coefficient (D) and higher heterogeneity of perfusion parameters: D* and F on IVIM MRI. No macroscopic changes consistent with PPAP were identified at any MRI. 21 patients subsequently underwent computer tomography imaging for clinical worsening, and 6 have PPAP confirmed. Conclusions: PPAP is characterized by early biochemical alteration, without correlation between severity and enzymes elevation. Macroscopic radiologic changes appear later and correlate with the most severe clinical pictures. This paper paves the ground for future prospective series validating correlations between biochemical and radiological features, eventually leading to changes in clinical practice management.

Ellagic acid attenuates liver toxicity induced by valproic acid in rats

Valproic acid is a commonly used drug for many psychiatric disorders, particularly for epilepsy. However, it has been reported that its use is associated with possible side effects including hepatotoxicity.The present study investigated the hepatoprotective effect of ellagic acid against valproic acid-induced hepatotoxicity in rats.Ellagic acid (60 mg/kg/day; p.o) was treated for one week, followed by concomitant injection of valproic acid (250 mg/kg/day; i.p.) for another 14 consecutive days to induce hepatocellular damage in adult Sprague–Dawley rats.Valproic acid showed a marked increase in serum enzyme activities, AST, ALT, ALP and GGT. In addition, it significantly increased MDA and NO along with a marked decline in reduced GSH content. At the same time, valproic acid administration resulted in marked elevation in hydroxyproline, TNF-α production and NF-kB expression. These results were confirmed by histopathological examination.Treatment with ellagic acid markedly attenuated valproic acid-induced hepatic injury in rats.

Lactic acid bacteria, Enterococcus faecalis Y17 and Pediococcus pentosaceus G11, improved growth performance, and immunity of mud crab (Scylla paramamosain)

Mud crabs (Scylla paramamosain), a commercially important cultured species in the southeastern region of China, is usually infected by Vibriosis or parasites, causing great economic losses in cultured farms. Previous studies have demonstrated that probiotics benefited in enhancing the immune response against invading pathogens in aquatic animals. In this study, the effects of dietary administration of lactic acid bacteria (LAB) (Enterococcus faecalis Y17 and Pediococcus pentosaceus G11) on growth performance and immune responses of mud crab were assessed. Both strains (Y17 and G11) showed an inhibitory activity against bacterial pathogens (Aeromonas hydrophila, Vibrio parahaemolyticus, Vibrio alginolyticus, Staphylococcus aureus, and β Streptococcus), and a wide pH tolerance range of 2–10. In vivo, mud crabs were fed a control diet and experimental diets supplemented with 109 cfu g−1 diet either Y17 or G11 for 6 weeks before subjecting to a challenge test with V. parahaemolyticus for 12 h. The probiotic-supplemented diets had significant effects on weight gain and specific growth rate during the feeding trial. Increased serum enzyme activities of phenoloxidase, lysozyme, and SOD were observed in the hemolymph of mud crab in Y17 and G11-supplemented groups compared to that in the controls (P < 0.01). The significantly up-regulated expression of gene CAT, LYS, proPO, and SOD could be seen in hepatopancreas in G11-supplemented groups. After the pathogenicity test, the survival rate of Y17 + and G11 + V. parahaemolyticus groups was 66.67% and 80.00%, respectively, compared with 53.33% for the control groups. Taken together, dietary supplementation of Y17 and G11 strains were beneficial in mud crab, which could increase growth performance, modulate immune system and protect the host against V. parahaemolyticus infection.

Effect of Ethanol Leaf Extract of &amp;lt;i&amp;gt;Vernonia amygdalina&amp;lt;/i&amp;gt; on Some Indices of Liver, Kidney Function and Lipid Profile in Theobromine Intoxicated Male Albino Wistar Rats

The effect of ethanol leaf extract of <i>Vernonia amygdalina</i> on some indices of liver, kidney function and lipid profile in male albino Wistar rats intoxicated with theobromine was investigated. Thirty (30) male Wistar rats weighing between 140 g – 160 g used for the study were divided into 6 groups with 5 animals in each group. Group I served as control while Group 2 received 700 mg/kg bw of theobromine daily for 4 days. Group 3 received 400 mg/kg bw of <i>V. amygdalina</i> leaf extract daily for 21 days while Groups 4 and 5 were treated with 400 mg/kg bw of <i>V. amygdalina</i> leaf extract for 21 days before and after intoxication with 700 mg/kg bw of theobromine for 4 days respectively. Group 6 was given 700 mg/kg bw of theobromine daily for 4 days and then allowed for 21 days without treatment. Serum was obtained from whole blood and used to determine activities of some serum enzymes and lipid profile as well as kidney function. The liver, kidney and heart were excised and used for histological studies. The results show significantly increased serum enzyme activities, total cholesterol and LDL cholesterol concentration in Group 2 compared to the control (P < 0.05). HDL cholesterol was significantly decreased in theobromine treated group when compared to Group 1 (P < 0.05). Administration of <i>V. amygdalina</i> leaf extract alone showed results close to those of the control. Group 4 showed decreased serum enzyme activities, decreased concentration of total cholesterol and LDL cholesterol while HDL cholesterol was increased significantly when compared to Group 2. Group 5 also showed a significant difference in the biochemical indices when compared to Group 2 while Group 6 show decreased serum enzyme activity that was significant when compared to Group 2. The urea and creatinine concentrations were significantly increased in theobromine intoxicated animals while administration of <i>Vernonia amygdalina</i> normalised these parameters. Histology of the liver, kidney and heart revealed altered cellular architecture following administration of theobromine (Group 2) while normal histological features were restored after treatment with ethanol leaf extract of <i>V. amygdalina</i>. The study has demonstrated that ethanol leaf extract of <i>Vernonia amygdalina</i> ameliorate and protect liver, kidney and heart of male albino Wistar rats against theobromine induced toxicity and modulates the adverse effects on lipid profile.

Serum prolidase enzyme activity in obese subjects and its relationship with oxidative stress markers

BackgroundThe relationship between increased serum enzyme activity of prolidase and increased rate of collagen turnover in the arterial wall has been asserted in previous studies. Collagen reflects much of the strength to the connective tissue involved in the arterial wall. Atherosclerosis is very common vessel disease and oxidative stress plays a pivotal role in the etiopathogenesis. Our objective was to examine the serum enzyme activity of prolidase and its possible relationships with oxidative stress parameters in obese subjects. MethodsOur present study was conducted 27 obese subjects and 26 age-matched healthy control subjects. The serum enzyme activity of prolidase in all study population was evaluated spectrophotometrically. Oxidative stress levels in obese subjects were analyzed with total antioxidant capacity (TAC) and total oxidant status (TOS) as well as oxidative stress index (OSI). ResultsObese subjects have higher serum TOS and OSI indicators as well as prolidase activity than those in control subjects (for all; p<0.001). Moreover, obese subjects have lower levels of TAC than in those in healthy subjects (p<0.001). In the Pearson's correlation analysis, enzyme activity of prolidase was positively related with TOS (p<0.001, r=0.529) and OSI (p<0.001, r=0.519) as well as BMI (p<0.001, r=0.692) and inversely related with TAC (p<0.05, r=−0.405) in obese subjects. ConclusionsIncreased serum prolidase activity and decreased antioxidant levels are likely to be a results of increased of oxidative stress levels in obese subjects. The significantly correlation between increased oxidative stress and increased prolidase activity may play a pivotal role in etiopathogenesis of atherosclerotic cardiovascular diseases in obese subjects.

Toxicity of white snakeroot (Ageratina altissima) and chemical extracts of white snakeroot in goats.

White snakeroot (Ageratina altissima) is a sporadically toxic plant that causes trembles in livestock and milk sickness in humans that drink tainted milk. The putative toxin in white snakeroot is tremetone and possibly other benzofuran ketones, even though it has not been demonstrated in vivo. Toxic white snakeroot was dosed to goats, and they developed clinical signs of poisoning, exercise intolerance, significant increases in serum enzyme activities, and histological changes. Tremetone and the other benzofuran ketones were extracted with hexane; the extracts and residues were analyzed for tremetone and dosed to goats at tremetone and benzofuran ketone concentrations similar to the original plant material. However, none of the dosed goats developed the disease. The results demonstrate for the first time that white snakeroot is a potent myotoxin in goats and that other compound(s), which may be lost or modified during the extraction process, could be involved in causing trembles and milk sickness.

Protective Role of Probiotic Lactic Acid Bacteria Against Dietary Fumonisin B1-induced Toxicity and DNA-Fragmentation in Sprague-Dawley Rats

The genus Fusarium, especially F. verticillioides and F. proliferatum, has been found in several agricultural products worldwide, especially in maize. Regardless the occurrence of symptoms, the presence of Fusarium in maize constitutes an imminent risk due to its ability to produce fumonisins, mycotoxins with proven carcinogenic effect on rats, swine, and equines and already classified as possible carcinogens to humans. The toxicity of incremental levels of fumonisin B1 (FB1), that is, 50, 100, and 200 mg FB1/kg diet, and the role of Lactobacillus delbrueckii subsp. lactis DSM 20076 (LL) and Pediococcus acidilactici NNRL B-5627 (PA) supplementation in counteracting the FB1 effects in intoxicated rats were monitored over a period of 4 weeks. Effects on the feed intake and body weight gain were noticed. A significant (p ≤ 0.05) increase in the level of liver and kidney functions markers and DNA fragmentation was also noticed in rat groups T100 and T200. The lactic acid bacteria (LAB) supplementation could bring back the normal serum biochemical parameters in rats fed on fumonisin B1-contaminated diets (T50 and T100) compared to FB1-treated groups. In rats of high-dosage dietary groups supplemented with LAB (T200-LL and T200-PA), the supplementation reduced the serum activity levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatinine by 11.3, 11.9, 32, and 20%, respectively. DNA fragmentations were observed in the rat group treated with 200 mg FB1 after 3 weeks, while fragmentation was noticed in treated groups with 100 and 200 mg FB1 after 4 weeks. No DNA fragmentation was apparent in FB1-treated rats co-administered the LL or PA strain. These results suggest that in male rats consuming diets containing FB1, there is a time- and dose-dependent increase in serum enzyme activities and DNA lesions. Moreover, Lb. delbrueckii subsp. lactis (LL) and P. acidilactici (PA) strains have a protective effect against antigenotoxicity and precancerous lesions.

Protection against phalloidin-induced liver injury by oleanolic acid involves Nrf2 activation and suppression of Oatp1b2

This study utilized pharmacological activation of Nrf2 with oleanolic acid (OA, 22.5mg/kg, sc for 4 days) and the genetic alteration of Nrf2 (Nrf2-null, wild-type, and Keap1-HKO mice) to examine the role of Nrf2 in protection against phalloidin hepatotoxicity. Mice were given phalloidin (1.5mg/kg, ip for 8h) to examine liver injury and the expression of toxicity-related genes. Phalloidin increased serum enzyme activities and caused extensive hepatic hemorrhage and necrosis in Nrf2-null and wild-type mice, but less injury was seen in Keap1-HKO mice and OA-pretreated mice. Phalloidin increased the expression of neutrophil-specific chemokine mKC and MIP-2 in Nrf2-null and WT mice, but such increases were attenuated in Keap1-HKO and OA-pretreated mice. Phalloidin increased, while Nrf2 activation attenuated, the expression of genes involved in acute-phase response (Ho-1) and DNA-damage response genes (Gadd45 and Chop10). Phalloidin is taken up by hepatocytes through Oatp1b2, but there was no difference in basal and phalloidin-induced Oatp1b2 expression among Nrf2-null, wild-type, and Keap1-HKO mice. In contrast, OA decreased phalloidin-induced Oatp1b2. Phalloidin activated MAPK signaling (p-JNK), which was attenuated by activation of Nrf2. In conclusion, this study demonstrates that protection against phalloidin hepatotoxicity by OA involves activation of Nrf2 and suppression of Oatp1b2.

Enzymes and muscle diseases

Skeletal muscle disorders may result in release of muscle enzymes into the circulation and give increased serum enzyme activity. A variety of enzymes routinely determined in the clinical laboratory may be elevated, but creatine kinase is the enzyme present in the highest concentration in muscle, and in every variety of muscle disease is the serum enzyme which shows the greatest incidence and degree of elevation. Aspartate aminotransferase is the enzyme associated most significantly with inflammation. A diagnostic algorithm based on the combined measurement of creatine kinase, aspartate aminotransferase and aldolase has been found to discriminate muscular dystrophies from polymyositis and other myopathies. This combination of laboratory tests has diagnostic application and thus allows the clinician to better select patients who need to have a skeletal muscle biopsy as a diagnostic procedure.

Antidotal effects of dimethyl sulphoxide against paracetamol-, bromobenzene-, and thioacetamide-induced hepatotoxicity.

In mice the hepatotoxic effects of paracetamol (0.5-1.0 g kg-1, orally) as evidenced by increased serum enzyme activities of the aminotransferases and sorbitol dehydrogenase were dose-dependently inhibited by simultaneous treatment with dimethyl sulphoxide (DMSO 0,25-1.0 g kg-1, i.p.). DMSO was also active against bromobenzene- and thioacetamide-induced hepatotoxicity, but failed to protect mice against carbon tetrachloride-induced liver damage. Hepatic glutathione depletion in mice amounting to 94% after paracetamol (0.5 g kg-1, orally) and to 60% after bromobezene (0.25 ml kg-1, orally) was dose-dependently reduced by the simultaneous administration of DMSO(0.25--1.0 G KG-1, I.P.). This indicates less conjugation of the toxic metabolites of paracetamol and bromobenzene to liver glutathione (G-SH) in the presence of DMSO.

Effects of perfluorooctanoic acid (PFOA) exposure to pregnant mice on reproduction

Perfluorooctanoic acid (PFOA) has similar characteristics to perfluorooctane sulfonate (PFOS) in reproduction toxicity featured by neonatal death. We found that PFOS exposure to mice during pregnancy led to intracranial blood vessel dilatation of fetuses accompanied by severe lung collapse which caused neonatal mortality. Thus, we adopted the corresponding experimental design to PFOS in order to characterize the neonatal death by PFOA. Pregnant ICR mice were given 1, 5 and 10 mg/kg PFOA daily by gavage from gestational day (GD) 0 to 17 and 18 for prenatal and postnatal evaluations, respectively. Five to nine dams per group were sacrificed on GD 18 for prenatal evaluation; other 10 dams were left to give birth. No maternal death was observed. The liver weight increased dose-dependently, with hepatocellular hypertrophy, necrosis, increased mitosis and mild calcification at 10 mg/kg. PFOA at 10 mg/kg increased serum enzyme activities (GGT, ALT, AST and ALP) with hypoproteinemia and hypolipidemia. PFOA treatment reduced the fetal body weight at 5 and 10 mg/kg. Teratological evaluation showed delayed ossification of the sternum and phalanges and delayed eruption of incisors at 10 mg/kg, but did not show intracranial blood vessel dilatation. Postnatal evaluation revealed that PFOA reduced the neonatal survival rate at 5 and 10 mg/kg. At 5 mg/kg pups were born alive and active and 16% died within 4 days observation, while all died within 6 hr after birth at 10 mg/kg without showing intracranial blood vessel dilatation. The cause of neonatal death by PFOA may be different from PFOS.

Haematological and serum biochemical response of growing rabbit bucks fed dietary fumonisin B 1

An experiment was conducted with 48 crossbred rabbits (49 days old) averaging 757.5 ± 0.50 g to assess haematological and serum biochemical response of growing rabbits exposed to varied levels of dietary fumonisin of 0.1, 5.0, 7.5 and 10 mg fumonisin B1/kg diet containing in diets 1 (control) 2, 3 and 4 respectively, for a period of 12 weeks. Blood samples were collected from the animals through the ear vein, after the feeding trial, for haematological studies and serum biochemistry. Results showed that packed cell volume, haemoglobin concentration and erythrocytes of rabbits fed diets containing 7.5 and 10.0 mg fumonisin B1/kg were significantly (P significantly (P 0.05) different among dietary treatments. However, lymphocytes of animals fed control diet were significantly (P Platelets and blood constants (MCV, MCH and MCHC) were not significantly (P > 0.05) different among the diets. Serum total protein, albumin and albumin-globulin ratio significantly (P with increase in the dietary fumonisin levels. Serum total protein of rabbits fed diets 3 (5.20 g/dl) and 4 (5.03 g/dl) were identical but both were significantly (P and the control (6.20 g/dl). Urea decreased while creatinine increased apparently with increase in the dietary fumonisin levels. Among the serum enzyme activities examined, AST and ALP were significantly (P fumonisin B1 above 5.0 mg kg-1 in the diet of growing rabbits significantly altered haematological parameters and induced anaemic condition in the animals. It also depressed serum total protein and enhanced abnormal increase in serum enzyme activities, which is an indication of organ toxicity by cellular destruction induced by the toxin most especially when fed at 7.5 and 10.0 mg fumonisin B1/Kg diet.

Haematological and serum biochemical response of growing rabbit bucks fed dietary fumonisin B1

An experiment was conducted with 48 crossbred rabbits (49 days old) averaging 757.5 ± 0.50 g to assess haematological and serum biochemical response of growing rabbits exposed to varied levels of dietary fumonisin of 0.1, 5.0, 7.5 and 10 mg fumonisin B1/kg diet containing in diets 1 (control) 2, 3 and 4 respectively, for a period of 12 weeks. Blood samples were collected from the animals through the ear vein, after the feeding trial, for haematological studies and serum biochemistry. Results showed that packed cell volume, haemoglobin concentration and erythrocytes of rabbits fed diets containing 7.5 and 10.0 mg fumonisin B1/kg were significantly (P 0.05) different among dietary treatments. However, lymphocytes of animals fed control diet were significantly (P 0.05) different among the diets. Serum total protein, albumin and albumin-globulin ratio significantly (P < 0.05) decreased with increase in the dietary fumonisin levels. Serum total protein of rabbits fed diets 3 (5.20 g/dl) and 4 (5.03 g/dl) were identical but both were significantly (P < 0.05) lower than those fed diets 2 (5.60 g/dl) and the control (6.20 g/dl). Urea decreased while creatinine increased apparently with increase in the dietary fumonisin levels. Among the serum enzyme activities examined, AST and ALP were significantly (P < 0.05) elevated in the serum of animals fed diets 3 and 4 than those fed diets 2 and the control. ALT, AST and ALP were significantly (P < 0.05) highest (94.33, 70.00 and 17.37 i.u/l respectively) in animals fed diet 4 containing 10 mg fumonisin B1/Kg. These results suggest that fumonisin B1above 5.0 mg kg-1 in the diet of growing rabbits significantly altered haematological parameters and induced anaemic condition in the animals. It also depressed serum total protein and enhanced abnormal increase in serum enzyme activities, which is an indication of organ toxicity by cellular destruction induced by the toxin most especially when fed at 7.5 and 10.0 mg fumonisin B1/Kg diet. Key words: Rabbits, haematology, serum biochemistry, dietary fumonisin B1.

Review of Hemoglobin-Induced Myocardial Lesions

Over 100 preclinical studies in several small and large animal species were performed to evaluate the safety and efficacy of diaspirin cross-linked hemoglobin (DCLHb; Baxter Healthcare Corp.) as an oxygen therapeutic. During the preclinical evaluation of DCLHb, myocardial lesions were observed following the administration of DCLHb to certain species. These lesions were characterized as minimal to moderate, focal-to-multifocal myocardial degeneration and/or necrosis that were scored using a severity scale of minimal to marked in relative severity. The lesions were typically observed 24-48 h after single topload infusions of DCLHb into rhesus monkeys or pigs at doses as low as 200 or 700 mg/kg, respectively. Dogs, sheep, and rats did not develop these lesions after single-dose administrations of DCLHb. The left ventricular myocardium, typically near the base of or including the papillary muscles, was the most severely affected region, followed by the intraventricular septum and the right ventricle. The left and right atria were usually not affected. In a study in rhesus monkeys, morphometric analysis revealed that these lesions comprised less than 3% of the total myocardium. Although increases in serum enzyme activities (AST, CK, LDH) were observed after infusion of DCLHb, myocardial-related isoenzymes did not increase. ECG analysis and echocardiography were not altered by these lesions, and there was no observable adverse effect on myocardial function. Polymerization of DCLHb reduced, but did not eliminate, the incidence and severity of the lesions. However, infusion of hemoglobin solutions with reduced reaction rates with nitric oxide (NO) resulted in a significant decrease in lesion incidence and severity, while administration of L-NAME, an NO synthase inhibitor, resulted in the appearance of lesions that were indistinguishable from those induced by hemoglobin, suggesting that reduction in normal NO levels is an important mechanistic factor. Overall, the presence of myocardial lesions represents a histopathologic finding that must be considered during the preclinical testing and development of new HBOCs.

Morphological and biochemical effects of a low ethanol dose on rat liver regeneration: role of route and timing of administration.

We have demonstrated that in rats subjected to partial hepatectomy (PH), the regenerating liver had an enhanced metabolism of ethanol, which largely depended on the route and timing of ethanol administration. Therefore, the influence of the administration route and timing for ethanol-induced deleterious effects on the regenerating rat liver was evaluated in animals subjected to 70% PH. Remnant liver showed moderate fatty infiltration, extended distortion of hepatocellular structure, and high mitotic index. Intragastric ethanol administration (1.5 g/kg body weight) considerably reduced the PH-induced changes in liver structures. Ethanol treatment also decreased liver thymidine kinase activity, serum albumin, and glucose levels. Intraperitoneal administration of the same ethanol dose to PH rats promoted lesser alterations on liver regeneration. Independently of its administration route, ethanol abruptly shortened a PH-induced selective increase in serum enzyme activities. These data suggest that the inhibitory effect of a low dose of ethanol on PH-induced liver regeneration is dependent on the timing and route of administration.

Contraction-induced injury to the extensor digitorum longus muscles of rats: the role of vitamin E.

Three days after a protocol of 225 pliometric (lengthening) contractions was administered to in situ extensor digitorum longus muscles of rats, the force deficit was 64 +/- 7% and the percentage of damaged muscle fibers was 38 +/- 5% of the control values. We then tested the hypothesis that at 3 h and 3 days after the protocol an elevation in the muscle vitamin E content would decrease the force deficit, the percentage of damaged muscle fibers, and the serum activities of creatine kinase and pyruvate kinase. The 5-8 days of intravenous injections of alpha-tocopherol increased muscle vitamin E content threefold compared with vehicle (ethanol)-treated rats. Despite the difference in vitamin E content, the force deficit and number of damaged fibers were not different. After the contraction protocol, the serum creatine kinase and pyruvate kinase activities of the vehicle-treated rats increased fourfold at 3 h and twofold at 3 days, whereas the vitamin E-treated rats showed no change. We conclude that vitamin E treatment did not ameliorate either the induction of the injury or the more severe secondary injury at 3 days. Despite the absence of evidence for an antioxidant function, the lack of any increase in serum enzyme activities for vitamin E-treated rats at 3 h and 3 days supported a role for vitamin E in the prevention of enzyme loss after muscle damage.