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PubMed1999

[Mobilization of alpha-glutathione S-transferase in the anesthetized patient].

OBJECTIVE: To measure and assess changes in plasma concentrations of alpha glutathione S-transferase (alpha-GST) during and after anesthesia with isoflurane, desflurane and propofol. PATIENTS AND METHODS: Study of 90 ASA I and II patients scheduled for lumbar back surgery under general anesthesia assigned randomly to one of three groups to receive anesthetic maintenance with isoflurane, desflurane or propofol. We measured plasma levels of alpha-GST, aspartate aminotransferase aspartate, alanine aminotransferase, alkaline phosphatase, pseudocholinesterase, gamma glutamyltransferase and total bilirubin at baseline and several times during and after surgery. RESULTS: Changes in plasma levels of alpha-GST were detected in all three groups, the tendency to increase reaching its peak with the sample taken at the end of anesthesia. The ranges considered normal were not exceeded in any of the patients studied. CONCLUSIONS: By measuring alpha-GST changes in plasma, we have detected signs of disturbance in hepatocellular integrity after anesthesia with all three maintenance agents used. However, the slight and transitory nature of the events confirms the scarce hepatotoxic potential of isoflurane, desflurane and propofol.

Adolescent↗

PubMed2000

Protective effect of N-acetylcysteine on rat liver cell membrane during methanol intoxication.

Methanol is oxidized in-vivo to formaldehyde and then to formate, and these processes are accompanied by the generation of free radicals. We have studied the effect of N-acetylcysteine on liver cell membrane from rats intoxicated with methanol (3.0 g kg(-1)). Evaluation of the effect was achieved by several methods. Lipid peroxidation and surface charge density were measured. An ultrastructural study of the liver cells was undertaken. The concentration of marker enzymes of liver damage (alanine aminotransferase and aspartate aminotransferase) in blood serum was measured. Methanol administration caused an increase in lipid peroxidation products (approximately 30%) as well as in surface charge density (approximately 60%). This might have resulted in the membrane liver cell damage visible under electron microscopy and a leak of alanine aminotransferase and aspartate aminotransferase into the blood (increase of approximately 70 and 50%, respectively). Ingestion of N-acetylcysteine with methanol partially prevented these methanol-induced changes. Compared with the control group, lipid peroxidation was increased by approximately 3% and surface charge density by approximately 30%. Alanine aminotransferase and aspartate aminotransferase activity increased by 9 and 8%, respectively, compared with the control group. The results suggested that N-acetylcysteine was an effective antioxidant in methanol intoxication. It may have efficacy in protecting free radical damage to liver cells following methanol intoxication.

Acetylcysteine↗

PubMed2004

Hyaluronic acid and chondroitin-4-sulphate treatment reduces damage in carbon tetrachloride-induced acute rat liver injury.

Oxidative stress is involved in the pathogenesis of chemically mediated liver injury. Since glycosaminoglycans possess antioxidant activity, the aim of this work was to assess the protective effects of hyaluronic acid and chondroitin-4-sulphate treatment in a model of carbon tetrachloride-induced liver injury. Liver damage was induced in male rats by an intraperitoneal injection of carbon tetrachloride (1 ml/kg in vegetal oil). Serum alanine aminotransferase and aspartate aminotransferase, hepatic malondialdehyde, plasma TNF-alpha, hepatic reduced glutathione and catalase, and myeloperoxidase, an index of polymorphonuclear infiltration in the jeopardised hepatic tissue, were evaluated 24 h after carbon tetrachloride administration. Carbon tetrachloride produced a marked increase in serum alanine aminotransferase and aspartate aminotransferase activities, primed lipid peroxidation, enhanced plasma TNF-alpha levels, induced a severe depletion of reduced glutathione and catalase, and promoted neutrophil accumulation. Intraperitoneal treatment of rats with hyaluronic acid (25 mg/kg) or chondroitin-4-sulphate (25 mg/kg) failed to exert any effect in the considered parameter, while the combination treatment with both glycosaminoglycans (12,5 + 12,5 mg/kg) decreased the serum levels of alanine aminotransferase and aspartate aminotransferase, inhibited lipid peroxidation by reducing hepatic malondialdehyde, reduced plasma TNF-alpha, restored the endogenous antioxidants, and finally decreased myeloperoxidase activity. These results suggest that hyaluronic acid and chondroitin-4-sulphate possess a different antioxidant mechanism and consequently the combined administration of both glycosaminoglycans exerts a synergistic effect with respect to the single treatment.

Alanine Transaminase↗

PubMedDate not supplied

Ginkgo biloba extract improves oxidative organ damage in a rat model of thermal trauma.

This study was designed to determine the possible protective effect of Ginkgo biloba extract (EGb) against oxidative organ damage distant from the original burn wound. Under brief ether anesthesia, the shaved dorsum of the rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10 seconds. EGb (50 mg/kg/day) or saline was administered intraperitoneally immediately and at 12 hours after the burn injury. Rats were decapitated 24 hours after burn injury and tissue samples from the liver and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen contents. Formation of reactive oxygen species in the tissue samples was monitored by the chemiluminescence technique. Tissues also were examined microscopically. Blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase levels and tumor necrosis factor- and lactate dehydrogenase activity were assayed in serum samples. Severe skin scald injury (30% TBSA) caused a significant decrease in GSH levels and significant increases in MDA levels, MPO activity, and collagen content of hepatic and renal tissues. Treatment of rats with EGb significantly increased the GSH level and decreased the MDA level, MPO activity, and collagen contents. Similarly, serum alanine aminotransferase, aspartate aminotransferase, and blood urea nitrogen levels, as well as lactate dehydrogenase and tumor necrosis factor-, were increased in the burn group as compared with the control group. However, treatment with EGb reversed all these biochemical indices, as well as histopathological alterations that were induced by thermal trauma. Our results show that thermal trauma-induced oxidative damage in hepatic and renal tissues is protected by the administration of EGb, with its antioxidant effects. Therefore, its therapeutic role as a "tissue injury-limiting agent" must be further elucidated in oxidant-induced tissue damage.

Animals↗

PubMed2005

Adrenomedullin and its binding protein attenuate the proinflammatory response after hemorrhage.

OBJECTIVE: The neuroendocrine response to hemorrhage is to maintain perfusion to the heart and brain, often at the expense of other organ systems. Systemic inflammation and tissue injury are important components of pathophysiologic consequences of hemorrhage. We have recently shown that administration of adrenomedullin (AM, a potent vasodilator peptide) and adrenomedullin binding protein-1 (AMBP-1) prevented the transition from the hyperdynamic to the hypodynamic stage in the progression of sepsis. However, the effect of AM/AMBP-1 on the inflammatory response after hemorrhage remains unknown. We therefore hypothesized that administration of AM/AMBP-1 during fluid resuscitation in hemorrhaged animals (i.e., posttreatment) attenuates tissue injury and the proinflammatory response. DESIGN: Prospective, controlled, and randomized animal study. SETTING: A research institute laboratory. SUBJECTS: Male adult rats. INTERVENTIONS: Rats were bled, and then a mean arterial pressure was maintained at 40 mm Hg for 90 mins. They were then resuscitated by infusion of four times the volume of shed blood using Ringer's lactate solution for 60 mins. MEASUREMENTS AND MAIN RESULTS: Fifteen minutes after the beginning of resuscitation, AM (12 microg/kg of body weight) in combination with AMBP-1 (40 microg/kg of body weight) was administered via a femoral venous catheter for 45 mins. Blood samples were collected 4 hrs postresuscitation and assayed for levels of liver enzymes (i.e., alanine aminotransferase and aspartate aminotransferase), lactate, creatinine, proinflammatory cytokines tumor necrosis factor and high mobility group box 1, and anti-inflammatory cytokine interleukin-10. The results indicate that levels of alanine aminotransferase, aspartate aminotransferase, creatinine, lactate, tumor necrosis factor, and high mobility group box 1 markedly elevated after hemorrhage and resuscitation, and AM/AMBP-1 treatment significantly attenuated these increases. In contrast, the serum concentration of anti-inflammatory cytokine interleukin-10 was increased by the treatment of AM/AMBP-1. Moreover, AM/AMBP-1 treatment significantly improved the survival rate from 35% in vehicle-treated animals to 73% in AM/AMBP-1-treated animals in a low-volume resuscitation model of hemorrhage. CONCLUSION: The combined administration of AM and AMBP-1 effectively suppresses hemorrhage-elicited organ injury and reduces hemorrhage-induced mortality, partly through down-regulation of proinflammatory cytokines (tumor necrosis factor and high mobility group box 1) and up-regulation of the anti-inflammatory cytokine interleukin-10.

Adrenomedullin↗

PubMed2003

Screening for statin-related toxicity: the yield of transaminase and creatine kinase measurements in a primary care setting.

BACKGROUND: Recommendations for monitoring levels of transaminases (alanine aminotransferase and aspartate aminotransferase) and of creatine kinase (CK) in patients taking 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) vary and are not based on data from clinical practice. We performed a study to determine the yield of routine screening of aminotransferase and CK levels among patients taking statins. METHODS: We performed a retrospective review of a primary care practice's computerized medical record. A computerized search identified all patients with a statin on their medication list and gave their alanine aminotransferase, aspartate aminotransferase, and CK values for 1998. We reviewed the records of all patients for whom these values were significantly or moderately abnormal to determine the values' relationship to statin therapy and outcomes. RESULTS: During the year of the study, 1014 (85%) of the 1194 patients who had a statin on their medication list had at least 1 monitoring test performed. Of these 1014 patients, 10 (1.0%) had a significant elevation and 5 (0.5%) a moderate elevation of transaminase levels, but none of these abnormalities appeared to be related to statin use. Moreover, 6 (0.9%) patients had at least 1 significantly abnormal CK value but it did not appear to be attributable to a statin; and of the 14 (2.1%) patients who had a moderate CK elevation, it was potentially due to a statin in only 2. There were no documented adverse sequelae associated with these abnormal results. CONCLUSIONS: In this study of statin use in a primary care practice, routine monitoring revealed no cases of significantly or moderately abnormal transaminase values attributable to statins. No significantly abnormal and only 2 moderately abnormal CK values were potentially attributable to statin use. This study questions the usefulness of routine measurement of transaminase and CK levels in all patients taking statins.

Alanine Transaminase↗

PubMed1987

Rotavirus gastroenteritis. Clinical and laboratory features and use of the Rotazyme test.

Clinical and laboratory features of 86 infants admitted with diarrhea and dehydration were evaluated prospectively. Human rotavirus (HRV) infection was documented in 35 infants (41%) by the Rotazyme test. Those with HRV gastroenteritis (HRV+ group) had a shorter duration of diarrhea prior to admission, more severe dehydration on presentation, and a longer hospital course than the HRV-negative (HRV-) group. Vomiting, fever, upper respiratory tract symptoms, otitis media, and cough were present in equal numbers of infants in both groups. The HRV+ infants had lower serum bicarbonate and higher serum albumin, alanine aminotransferase, aspartate aminotransferase, and uric acid concentrations than did the HRV- infants. Serum uric acid levels greater than 10 mg/dL (590 mumol/L) were present in 69% of HRV+ vs 29% of HRV- infants. The Rotazyme test was found to be a valuable tool in diagnosis; testing on two days increased the yield from 74% to 97% of all infants finally diagnosed as HRV+. The optimal time for testing was within the first five days of illness.

Diarrhea, Infantile↗

PubMed1991

Photodynamic therapy to treat tumors of the extrahepatic biliary ducts. A case report.

The poor survival rate of patients with extrahepatic bile duct tumors is well documented. Over the course of 4 years, we treated a white woman with diabetes diagnosed with histologically proven adenocarcinoma of the common bile duct with six injections of dihematoporphyrin ether followed by seven photodynamic therapy treatments to the biliary duct. As of July 1989, the patient was still alive, was not jaundiced, and had a Karnofsky performance status of 70. No changes occurred in any blood chemistry value from the time of injection to the time of photodynamic therapy. Of the transient elevations of some blood chemistry values and the white blood cell count, which occurred within 24 to 48 hours after photodynamic therapy, only those of alanine aminotransferase, aspartate aminotransferase, and amylase were significant.

Adenocarcinoma↗

PubMed1999

Prostate-specific antigen in acute hepatitis and hepatocellular carcinoma.

BACKGROUND: Prostate-specific antigen (PSA) is the most important tumor marker in prostate cancer diagnosis and follow-up. Its catabolism by the liver has not influenced its use as a prostate marker until the recent report of a significant increase in a man and a woman with acute hepatitis. In addition, PSA was detected in liver tumor extracts, which warranted its evaluation in liver cytolysis and hepatocellular carcinoma. In this study, PSA was evaluated in a cohort of both sexes presenting either acute hepatitis or hepatocellular carcinoima. METHODS: Forty-two patients with acute hepatitis (21 male patients, 21 female patients) and 54 patients with hepatocellular carcinoma (31 male patients, 23 female patients) were tested for PSA by equimolar immunoassay (Abbott AxSYM Total PSA, Abbott Diagnostics, Rungis, France) and for relevant liver biological parameters (alpha-fetoprotein, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and prothrombin rate). RESULTS: PSA was undetectable in all the female patients and was consistent with age in the males (PSA median and range in acute hepatitis, 0.36 microg/l (range, 0.05-1.3); in hepatocellular carcinoma, 0.36 microg/l (range, 0.02-3.9)). It did not correlate with alpha-fetoprotein and aminotransferases. CONCLUSIONS: Our results confirm the well-established reliability of PSA, and show that PSA remains a valid prostate marker in patients with acute hepatitis and hepatocellular carcinoma.

Acute Disease↗

PubMed1997

Risk factors for intrahepatic recurrence of hepatocellular carcinoma in cirrhotic patients treated by percutaneous ethanol injection.

BACKGROUND: Hepatocellular carcinoma (HCC) complicating cirrhosis has a high intrahepatic recurrence rate after treatment by surgical resection or percutaneous ethanol injection (PEI). In this study, certain clinical, biochemical, and pathologic parameters were evaluated as risk factors for intrahepatic tumor recurrence in liver segments different from that of the first neoplasm in a group of 57 cirrhotic patients with single HCC < 5 cm treated by PEI. METHODS: After PEI treatment of HCC, the patients were followed for a mean period of 33 +/- 16 months. The following pretreatment parameters were evaluated as predictors of tumor recurrence: age, gender, Child-Pugh score, hepatitis B virus surface antigen, hepatitis C virus antibodies, alanine aminotransferase, aspartate aminotransferase, alpha-fetoprotein (AFP) level before PEI, alcohol abuse, HCC size, HCC ultrasound pattern, HCC histologic grade, HCC capsule, and time from cirrhosis diagnosis. Furthermore, the posttreatment parameters of the AFP level 1 month after PEI and recurrence of HCC in the same liver segment were also evaluated. RESULTS: The cumulative 4-year intrahepatic recurrence rate of HCC was 62%. The log rank test indicated that, among pretreatment parameters, time from cirrhosis diagnosis > 6 years (P = 0.05) and AFP level before PEI of > 25 ng/mL (P = 0.00005) were significantly linked to tumor recurrence. Cox's proportional hazards model showed that only AFP level before PEI was independently associated with recurrence (P < 0.002). With regard to posttreatment parameters, an AFP level 1 month after PEI of > 13 ng/mL was shown to be significantly related to tumor recurrence by the log rank test (P < 0.0001). CONCLUSIONS: Cirrhotic patients with single HCC treated by PEI who have slightly increased serum levels of AFP before and/or after PEI treatment are at increased risk of intrahepatic tumor recurrence and should undergo a close follow-up program.

Adult↗

PubMed2000

Effect of Withania somnifera glycowithanolides on iron-induced hepatotoxicity in rats.

Glycowithanolides, consisting of equimolar concentrations of sitoindosides VII-X and withaferin A, isolated from the roots of Withania somnifera Dunal, have been reported to have an antioxidant effect in the rat brain frontal cortex and striatum. In the present study, the effect of 10 days of oral administration of these active principles, in graded doses (10, 20 and 50 mg/kg), was noted on iron overload (FeSo(4), 30 mg/kg, i.p.) induced hepatotoxicity in rats. Apart from hepatic lipid peroxidation (LPO), the serum enzymes, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, were assessed as indices of hepatotoxicity. Silymarin (20 mg/kg, p.o.) was used for comparison. Iron overload induced marked increase in hepatic LPO and serum levels of the enzymes, which was attenuated by WSG in a dose-related manner, and by silymarin. The results indicate that the reported use of WS in Ayurveda for hepatoprotection against heavy metals and other environmental toxins, may be due the antioxidant action of WSG.

Administration, Oral↗

PubMed2004

Genetic variability of hepatitis C virus NS3 protein in human leukocyte antigen-A2 liver transplant recipients with recurrent hepatitis C.

The association between the severity of chronic hepatitis C and the variability of the hepatitis C virus (HCV) genome remains controversial, but to our knowledge few data are available to date regarding T-cell epitope coding regions in transplant patients. In the current study, we identified 21 human leukocyte antigen (HLA)-A2-positive Spanish patients with chronic hepatitis C, 14 immunosuppressed liver transplant recipients, and 7 immunocompetent controls. Alanine aminotransferase, aspartate aminotransferase, viral load, and rate of fibrosis progression were determined. Genetic distances of HCV isolates and variations in epitopes of the HCV nonstructural 3 protein (NS3-1393 LIFCHSKKK and NS3-1406 KLVALGINAV) were compared between patients with slow or fast progression of fibrosis. Isolates from transplant patients with fast progression were found to be more divergent (P =.03), had a higher mean value of synonymous (dS) variations (P =.02), and some were differentiated in a phylogenetic tree, compared with isolates from patients with slow progression. The HLA-A2-restricted NS3-1406 epitope was found to be more variable (20 of 21 isolates differed from the prototype) compared with the A3-restricted NS3-1392 epitope (19% vs. 1.25% variation). A shift in the viral peptide was not detected in a subset of transplant patients, but was evident in two of three nontransplant patients with follow-up. There was no correlation noted between a particular amino acid variation and fibrosis progression (slow or fast) in either transplant or nontransplant patients. The results of the current study suggest that 1) there may be different HCV-1b strains in our geographic area, 2) immunosuppression appears to have little effect in amino acid variation at the HCV NS3-1406 epitope, and 3) variations over time might be more frequent in nonimmunosuppressed patients.

Adult↗

PubMed2006

Long-term biological consequences of donor right hepatectomy including the middle hepatic vein in adult-to-adult live donor liver transplantation.

The right lobe liver graft has become the workhorse of adult-to-adult live donor liver transplantation. Donor right hepatectomy is feasible only because of the immense regenerative ability of the liver. The long-term biological consequences of this very major donor procedure on the donor however are unknown. Twenty-nine donors of this procedure in our centre, all of whom included the middle hepatic vein, were studied. On long-term follow-up at a median of 47.4 months, there was a discernible but statistically insignificant decrease in size of the regenerated left lobe compared to the original whole liver volume. There was paradoxically a trend of incompleteness of regeneration in relation to the original liver volume for those with a larger remnant left lobe. The volume ratio of the regenerated left lobe to the original left lobe before hepatectomy was inversely proportional to the left lobe proportion preoperatively. This strong but inverse linear correlation reflected the good regenerative ability of the remnant left lobe. None of the donors developed thrombocytopenia. Although demonstrable decrease in white cell count, increase in serum alanine aminotransferase, aspartate aminotransferase, and creatinine did occur, the changes remained within normal limits and were of yet uncertain clinical significance. In conclusion, donor right hepatectomy including the middle hepatic vein is biologically acceptable to the live donor.

Adolescent↗

PubMed2006

Protective effects of Zingiber officinale (Zingiberaceae) against carbon tetrachloride and acetaminophen-induced hepatotoxicity in rats.

The effect of the ethanol extract of the rhizome of Zingiber officinale was tested against carbon tetrachloride (CCl(4)) and acetaminophen-induced liver toxicities in rats. Increases in serum and liver marker enzymes such as alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase as well as sorbitol and glutamate dehydrogenases were produced in normal rats that were not pretreated with the extract. However, extract-pretreated rats attenuated in a dose-dependent manner, CCl(4) and acetaminophen-induced increases in the activities of ALT, AST, ALP, LDH and SDH in the blood serum. The protective effect of the extract on CCl(4) and acetaminophen-induced damage was confirmed by histopathological examination of the liver. These results indicate that the oil from the rhizome of Zingiber officinale could be useful in preventing chemically induced acute liver injury.

Acetaminophen↗

PubMed1996

Preclinical toxicity evaluation of tepoxalin, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, in Sprague-Dawley rats and beagle dogs.

Tepoxalin [5- (4-chlorophenyl)-N-hydroxy-1-(4-methoxyphenyl)-N-methyl-1H-pyrazole -3-propanamide] is an orally active anti-inflammatory agent, which inhibits both cyclooxygenase and 5-lipoxygenase activities. The oral toxicity of tepoxalin was evaluated in 1- and 6-month rat (up to 50 mg/kg/day) and dog (up to 150 mg/kg bid) studies. In rats, increased liver weight, centrilobular hypertrophy, and hepatic necrosis were observed at dosages >/=20 mg/kg/day. Renal changes indicative of analgesic nephropathy syndrome (i.e., papillary edema or necrosis, cortical tubular dilatation) were seen at >/=15 mg/kg. In rats treated for 1 month, these hepatic and renal effects were largely reversible after a 1-month recovery period. Gastrointestinal erosions and ulcers were seen in female rats given 40 mg/kg/day for 6 months. Changes in clinical pathology parameters included decreases in red blood cell count, hemoglobin, and hematocrit mean values; elevation in platelet counts; and an increase in prothrombin and activated partial thromboplastin times. Mild increases in alanine aminotransferase, aspartate aminotransferase, and cholesterol were also noted in rats. Decreased erythrocyte parameters, increased leukocyte counts, and decreased total protein, albumin, and/or calcium were noted in some dogs in the 300 mg/kg/day group following 6 months of dosing. Small pyloric ulcerations were seen at 100 and 300 mg/kg/day dosages for up to 6 months. In both rats and dogs, no accumulation of tepoxalin or its carboxylic acid metabolite was detected in plasma following multiple dosing over a range of 5 to 50 mg/kg/day for rats and 20 to 300 mg/kg/day for dogs. Plasma concentrations of the carboxylic acid metabolite were severalfold higher than those of the parent compound. The no-effect dosages in rats (5 mg/kg/day) and dogs (20 mg/kg/day) were approximately one and six times the ED50 (3.5 mg/kg), respectively, for inhibition of inflammatory effects in the adjuvant arthritic rat without gastric mucosal damage. In terms of severity, the relative lack of gastrointestinal side effects, within the estimated therapeutic dose range, distinguishes tepoxalin from most marketed anti-inflammatory drugs.

Absorption↗

PubMedDate not supplied

TT virus (TTV) is not associated with acute sporadic hepatitis.

A novel virus, TT virus (TTV), recently discovered by Okamoto et al. in the serum of a patient with posttransfusion hepatitis, is thought to be one of the causative agents of blood-borne acute hepatitis. The association of this virus with acute sporadic hepatitis was evaluated. TTV DNA was detected in 4 (4.9%) of 81 cases of acute hepatitis A, in 5 (16.7%) of 30 cases of acute hepatitis B, in 1 (25.0%) of 4 cases of acute hepatitis C, in 1 (9.1%) of 9 cases of cytomegalovirus and Eppstein-Barr infection, and in 8 (13.6%) of 59 cases of acute hepatitis of unknown etiology. These positive rates of TTV in various etiologies did not differ significantly amongst each other, and were similar to those of healthy volunteers, i.e. 12.0% (12/100). The comparison of levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, hepaplastin test and prothrombin time between TT virus-positive and -negative patients did not show any differences. This indicates that TTV is neither a main causative agent of acute sporadic hepatitis of unknown etiology, nor does it affect the clinical features of acute hepatitis with already known etiology.

Acute Disease↗

PubMedDate not supplied

Changes in blood chemistry, hematology, and histology caused by a selenium/vitamin E deficiency and recovery in chicks.

Exudative diathesis, a condition caused by a selenium (Se)/vitamin E deficiency, was studied in chicks. Trios of chicks that showed clinical signs of exudative diathesis were matched for severity. One was injected subcutaneously with 0.5 mL distilled water, and the other two received 15 microg of Se in 0.5 mL distilled water. A chick fed a diet with supplemental Se also received 0.5 mL distilled water. Blood was collected from three chicks 2 d after injection, and from the other chick, 6 d after injection. After blood was collected, pectoral muscle and bone marrow were collected. Deficient chicks showed varying degrees of necrosis in pectoral muscle, whereas recovering chicks had extensive fibrosis in pectoral muscle. An analysis of blood showed differences in CO2, glucose, Se, glutathione peroxidase, alanine aminotransferase, aspartate aminotransferase, and creatine kinase. Heterophils and monocytes were increased in deficient chicks; lymphocytes, basophils, and hemoglobin decreased. After 6 d of recovery, all of the changes noted above were correcting toward normal. Eosinophils, in contrast, were unaffected by a deficiency, but increased in recovering chicks. It is hypothesized that cytokines associated with the inflammatory response accentuate the clinical signs of exudative diathesis.

Animals↗

PubMed1991

A long-term toxicological investigation on the effect of tris(maltolate)aluminum(III) in rabbits.

The toxicity of i.v. injected hydrophilic aluminum complex tris(maltolate)aluminum(III) was studied in New Zealand white rabbits for a period of time ranging from 5 to 63 wk. Animals were injected 3-5 times a week with 1 mL of 7.5 mM Al(malt)3 and one rabbit with a dose 10 times higher after 14 wk of treatment. Autopical examination was performed on all animals. Chemoclinical analysis (glucose, urea, creatinine, cholesterol, bilirubin, alanin aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl-transferase, LDH, CK, total protein, triglycerides, and Ca2+) gave no variation in treated animals with respect to the control. The toxicological data show a moderate systemic general toxicity at doses far higher than those used in similar previous experiments using Al(acac)3 (acac = 2,4 pentanedionate), a hydrolytically stable and more lipophilic aluminum(III) complex (1). The diversity of behavior is discussed in terms of metal speciation as well as respect to the thermodynamic and kinetic properties of the two complexes in aqueous solution. The toxicological model presented here emphasizes that neutral, water compatible aluminum(III) complexes are to be considered as promising tools for toxicological experiments providing biological models of human pathologies.

Aluminum↗