Serum Glutamic Oxaloacetic Transaminase Levels Research Articles

Supplementation of taurine and β-cyclodextrin to mice administered ethanol restores lipid metabolism and damaged liver

In this study we investigated the effects of taurine and β-cyclodextrin (β-CD) supplementation on lipid metabolism and hepatic cell damage in mice administered with ethanol. The supplemented mice consisted of a control (CO) group, an ethanol (AL) group, and an ethanol + taurine + β-CD (ATB) group. The ethanol (45 g/L) and/or taurine (76.5 mg/L) + β-CD (153 mg/L) treatments were administered for 6 months via the drinking water. At the termination of the treatment period the following measurements were made: serum and hepatic lipids, serum enzymes, and the extent of hepatic lipid peroxidation. The serum total cholesterol and triacylglycerol levels were higher in the AL group than in the CO and ATB groups. In the ATB group, there were significant decreases in total cholesterol and triacylglycerol levels, as well as a slight decrease in the low-density lipoprotein cholesterol level. Hepatic triacylglycerol and malondialdehyde levels were higher in the AL group than in the CO and ATB groups. Furthermore, the ATB group had significant decreases in hepatic triacylglycerol and malondialdehyde levels. The serum levels of glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, alkaline phosphatase, and lactate dehydrogenase were higher in the AL group than in the CO group. The ATB group had significant decreases in glutamic-pyruvic transaminase and the liver damage index, as well as slight decreases of glutamic-oxaloacetic transaminase, alkaline phosphatase, and lactate dehydrogenase. These data suggest that the combined supplementation of taurine and β-CD improves and restores lipid metabolism and liver cell damage in mice with ethanol-induced injuries.

Viral Interleukin-10 Gene Transfer Prevents Liver Ischemia–Reperfusion Injury: Toll-Like Receptor-4 and Heme Oxygenase-1 Signaling in Innate and Adaptive Immunity

Ischemia-reperfusion injury (IRI) contributes to early and late dysfunction of liver transplants. We have shown that sentinel Toll-like receptor-4 (TLR4) plays a key role in the activation of T cell immune responses during hepatic IRI. We have also documented that overexpression of heme oxygenase-1 (HO-1) exerts potent cytoprotective effects. This study analyzes how adenovirus (Ad)-based viral interleukin-10 (vIL-10) gene transfer affects TLR4 and HO-1 signaling in host innate and adaptive immunity during liver IRI. Using a partial lobar warm IRI model, groups of wild-type and HO-1(+/-) knockout (KO) mice were assessed for severity of hepatocellular damage after 90 min of warm ischemia followed by 6 hr of reperfusion. Both wild-type and HO-1 (+/-) KO mice treated with Ad-vIL-10 have shown improved hepatic function (serum glutamic-oxaloacetic transaminase levels), ameliorated histological signs of IRI (Suzuki's score), decreased neutrophil accumulation (myeloperoxidase activity), and depressed tumor necrosis factor-alpha/IL-1beta, IL-2/interferon-gamma, E-selectin, and macrophage inflammatory protein-2 expression. These effects were IL-10 dependent as treatment with neutralizing antibody re-created liver IRI. In contrast, untreated wild-type and HO-1 (+/-) KO mice, as well as wild-type and HO-1 (+/-) KO mice treated with Ad-beta-Gal, showed severe hepatocellular damage due to IRI. Unlike in controls, wild-type and HO-1 (+/-) KO mice treated with Ad-vIL-10 revealed markedly depressed TLR4 and NF-kappaB expression, along with increased HO-1 and Bcl-2/Bcl-x(L) expression, as compared with respective controls. Thus, vIL-10 gene transfer prevents hepatic IRI in association with depressed expression of innate TLR4, and adaptive Th1 cytokine/chemokine programs. The induction of antioxidant HO-1 and anti-apoptotic Bcl-2/Bcl-x(L) by vIL-10 exerts synergistic cytoprotective function against antigen-independent hepatic inflammatory response triggered by IRI.

Efficacy of Raphanus sativus in the treatment of paracetamol-induced hepatotoxicity in albino rats

In the present study, the efficacy of a methanol extract of Raphanus sativus root (RSME) is tested in albino rats that developed hepatic damage due to administration of paracetamol (100 mg/kg body weight) for 30 days. Twenty rats were divided into three experimental groups (E1, E2, E3) and one control group (EC). Two doses of RSME (80 and 120 mg/kg body weight) were administered orally to E1 and E2, respectively, and a mixture of RSME (120 mg/kg) and paracetamol (100 mg/kg) was administered to E3 for 21 days. Group EC and another group of normal rats (EN) that served as controls were administered distilled water. At the end of the experiment rats were bled to assay thiobarbituric acid reactive substances (TBARS), serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate aspartate transaminase (SGPT), reduced glutathione (GSH) and catalase. Results indicated that RSME reduced the levels of TBARS, SGOT and SGPT, and increased the level of GSH and the catalase activity in E1 and E2 as compared to the EC group. Group E3 showed decreases in TBARS, SGOT and SGPT levels, but the results were not statistically significant compared with the EN group. There was also a marked depletion in GSH level and catalase activity in this group. RSME reduced lipid peroxidation induced by paracetamol and brought the levels of SGOT and SGPT to normal, indicating liver recovery. It also brought about repletion of GSH levels and recovery of catalase activity. Results for group E3 indicated that RSME was not able to reverse the effects of paracetamol if administration continued.

Antioxidant activity of the oyster mushroom, Pleurotus ostreatus, on CCl 4-induced liver injury in rats

This study was undertaken to investigate the putative antioxidant activity of the oyster mushroom Pleurotus ostreatus on CCl 4-induced liver damage in male Wistar rats. Intraperitoneal administration of CCl 4 (2 ml/kg) to rats for 4 days resulted in significantly elevated ( p < 0.05) serum levels of glutamic oxaloacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT) and alkaline phosphatase (SALP) compared to controls. In the liver, significantly elevated levels ( p < 0.05) of malondialdehyde (MDA) and lowered levels ( p < 0.05) of reduced glutathione (GSH) were observed following CCl 4 administration. Quantitative and qualitative analysis of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) revealed lower activities of these antioxidant enzymes in the liver of CCl 4-administered rats. An analysis of the isozyme pattern of these enzymes revealed variations in relative concentration presumably due to hepatotoxicity. When rats with CCl 4-induced hepatotoxicity were treated with the extract of P. ostreatus, the serum SGOT, SGPT and SALP levels reverted to near normal, while the hepatic concentration of GSH, CAT, SOD and Gpx were significantly increased ( p < 0.05) and that of MDA significantly ( p < 0.05) lowered, when compared to CCl 4-exposed untreated rats. Histopathological studies confirmed the hepatoprotective effect conferred by the extract of P. ostreatus. These results suggest that an extract of P. ostreatus is able to significantly alleviate the hepatotoxicity induced by CCl 4 in the rat.

Effects of Sevoflurane on Biomechanical Markers of Hepatic and Renal Dysfunction After Coronary Artery Surgery

The purpose of this study was to compare the effects of a total intravenous and a volatile anesthetic regimen on biochemical markers of hepatic and renal dysfunction after coronary artery surgery. Prospective, double-blind, randomized clinical study. University hospital, single institutional. Three hundred twenty patients undergoing elective coronary artery surgery were divided into 2 different anesthetic protocols: propofol group (n = 160) and sevoflurane group (n = 160). Hemodynamic data were registered before the start of surgery, before the start of CPB, 15 minutes after the end of CPB, at arrival in the intensive care unit, and 6 and 12 hours after arrival in the intensive care unit. Serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum lactate dehydrogenase (LDH), and serum creatinine concentrations were measured before surgery, at arrival in the intensive care unit, and after 6, 12, 24, and 48 hours. Postoperative levels of serum SGOT, SGPT, and LDH increased transiently in both anesthetic groups, but the increase was significantly lower in the sevoflurane group compared with the propofol group. Creatinine levels remained largely unchanged in both groups. Postoperative biochemical markers of hepatic dysfunction were lower with a sevoflurane-based anesthetic regimen in patients undergoing coronary artery surgery with cardiopulmonary bypass.

넙치 실용배합사료개발을 위한 현장적용시험

This study was conducted to evaluate the effects of extruded pellet (EP) diets, as compared to a raw fish moist pellet (MP) diet for olive flounder, Paralichthys olivaceus, grown in commercial-scale aquaculture for 1 year. Four diets with duplication per diet were formulated for this experiment: two experimental EP diets (EP1 and EP2), one commercial EP diet (CEP), and a raw fish MP diet (MP). The MP diet consisted of 80% frozen horse mackerel and 20% commercial binder meal. Fish weighing <TEX>$30.1{\pm}0.1 g$</TEX> (<TEX>$mean{\pm}SD$</TEX>) were distributed randomly to each aquarium as a group of 2,600 fish. Weight gain (WG) and feed efficiency ratio (FER) of fish fed EP2 and MP were higher (P<0.05) than those of fish fed CEP, while those of fish fed EP1 did not differ (P>0.05) from those fed EP2 and MP. However, fish fed the MP diet had a higher survival rate than fish fed the other diets. Fish fed EP2 had higher serum, phospholipids and total protein levels, and lower levels of serum glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), and total cholesterol than fish fed MP (P<0.05). Dorsal muscle and liver proteins and lipid of fish fed EP1 were higher (P<0.05) than those of fish fed CEP, while those of fish fed EP1 and MP did not differ from those of fish fed EP2 (P>0.05). These results strongly suggest that EP1 could be developed to replace MP for grow-out stage production of olive flounder without adverse effects on growth performance.

Hepatoprotective and Antifatigue effects of Lactic acid bacteria (Lactobacillus acidophilus, Bifidobacterium bifidum and Streptococcus thermophilus) in SD rats and ICR mice

Lactobacillus acidophilus, Bifidobacterium bifidum and Streptococcus thermophilus are potent probiotic lactic acid bacteria (LAB) that used in commercial fermented dairy products. These strain are play a important roles in human health include a lowering the levels of serum cholesterol, vitamin synthesis, improving lactose intolerance, maintaining the balance of intestinal microflora and anti-cancer activity. The main aim of this study was investigate that hepatoprotective activity-carbon tetra chloride and ethanol (25%) induced liver injury in SD rats-and antifatigue effects were evaluated. To investigate the hepatoprotective effect, rats treated with CCl4 and ethanols were analyzed with serum glutamic pyruvic transaminase (s-GPT) and serum glutamic oxaloacetic transaminase (s-GOT) level. These lactic acid bacteria (LAB) could afford a significant protection in the alleviation of CCl4 and ethanol-induced hepatocellular injury. The antifatigue activity of LAB was studied in ICR mice, using forced swimming test, horizontal wire test and rotarod test. The LAB (orally inoculated mixture of LAB for 3weeks) showed a significant antifatigue effect in test group. These results suggested that LAB have hepatoprotective activity and antifatigue effect.

EVALUATION OF PARAOXONASE (PON) GLUTAMATE OXALOACETATE TRANSAMINASE (SGOT)

Objectives: This study was undertaken for the comparative evaluationof paraoxonase (PON) and Serum Glutamate Oxaloacetate Transaminase (SGOT) levels in male cardiac patients andnormal subjects and the evaluation of cardiac dysfunction by assaying the enzymes PON and SGOT. Study design:Prospective Period: Six months from June 2003 to Nov 2003. Setting: DHQ Hospital Faisalabad/ Department ofChemistry Agriculture University of Faisalabad. Method &amp; Materials: The blood of the male cardiac patients as wellas control subjects was collected and serum was separated, that was used for the determination of PON and SGOTactivity. Twenty blood samples from male cardiac patients from DHQ Faisalabad was collected. At the same time 20other male subjects which were not suffering from any active cardiac disease were selected as control. Ante-cubitalvenous blood samples without anticoagulant were centrifuged to obtain the serum. Results: Paraoxonase is presentin the blood on the HDL and it can break down the oxidized LDL to non-harmful products therefore the activity of HDLand LDL was determined along with other two parameters. It was observed that the cardiac male patients had lowactivity of PON and HDL as compared to normal. Whereas activity of SGOT and LDL was lower in normal subjects ascompared to the cardiac male patients. The activity of PON and HDL (56.86±0.94 U/ml), (14.58±0.14 mg/dl) is lowerin cardiac male patients as compared to normal (241±0.85 U/ml), (46.66±1.10 mg/dl)respectively, while SGOT (219.0±2U/ml and LDL (177.3±4.73 mg/dl) was greater as compared to the control (24.78±2.32 U/ml) and (119.2±1.08 mg/dl)respectively. Conclusion: It is concluded that there was an inverse correlation between serum PON and SGOT.

Electrocardiographic and Biochemical Evidence for the Cardioprotective Effect of Vitamin E in Doxorubicin-Induced Acute Cardiotoxicity in Rats

Cardiotoxicity is a major side effect limiting the use of doxorubicin, a potent chemotherapeutic agent, in the treatment of pediatric neoplastic diseases. The effect of vitamin E in doxorubicin-induced cardiotoxicity in rats has been studied. Eighteen Wistar male rats (age 60 - 100 days, weighing 175 - 260 g) were divided into three groups of six: group A (controls); group B (doxorubicin-treated rats); and group C (pretreatment with a high dose of vitamin E followed by doxorubicin treatment). The weights of the rats were measured daily. The rats were sacrificed seven days after the last dose of doxorubicin injection by an overdose of ether. Electrocardiogram (ECG) tracings were recorded before sacrificing the rats. The ECG tracings were then evaluated for rate and rhythm disorders by assessing the PR, ST, and QT intervals. In group B rats ECG tracings were taken three days after the completion of doxorubicin treatment, while in group C rats they were taken at the end of 2 weeks of vitamin E pretreatment and again 3 days after the completion of doxorubicin treatment. Serum levels of creatine phosphokinase (CPK-MB), lactic dehydrogenase (LDH), and serum glutamic oxaloacetic transaminase (SGOT) were assessed from an intracardiac blood sample taken at the time of sacrificing the rat. Mean weight ranged from 205 - 226 g. Mean total dose of doxorubicin in groups B and C ranged from 36 - 38 mg. The PR intervals in the three groups were recorded as 0.006, 0.070, 0.057 s for groups A, B, and C, respectively (p = 0.0024) and the QT interval as 0.023, 0.120, 0.088 s in groups A, B, and C, respectively (p = 0.00089). The ST elevation due to doxorubicin toxicity was significantly reversed by vitamin E treatment. The difference in the levels of CPK-MB and LDH between the three groups was found to be statistically significant. Serum SGOT levels also varied between the three groups but were not statistically significant. Vitamin E pretreatment prevented the PR, QT, and ST segment changes caused by doxorubicin. Vitamin E treatment helped to decrease the levels of CPK-MB and LDH that were increased due to myocardial damage caused by the doxorubicin. There is sufficient evidence to believe that vitamin E protects the rat myocardium from doxorubicin-induced damage.

Comparative antidiabetic activity of different fractions of methanolic extract of Zingiber officinale Roscoe in streptozotocin induced NIDDM rats

Earlier we have reported the antidiabetic activity of fresh juice of rhizomes of Zingiber officinale (Z. officinale) and its correlation with 5-HT receptor antagonism. Since 6-gingerol the marker compound of Z. officinale is reported to posses 5-HT anatgonistic activity, the present investigation, was undertaken to find out the concentration of 6-gingerol present in methanolic extract of Z. officinale and its different fractions (petroleum ether, toluene and chloroform). We also evaluated these fractions for antidiabetic activity in streptozotocin (STZ)-induced neonatal type 2 diabetic rats. Fasting glucose and insulin levels in non insulin dependent diabetes mellitus (NIDDM) rats were found to be significantly (P < 0.05) higher than control rats and these were significantly decreased by treatment with methanolic extract of Z. officinale and its fractions. The results of oral glucose tolerance test (OGTT) showed that methanolic extract and its fractions significantly (P < 0.05) decreased both STZ-induced increase in <TEX>$AUC_{glucose}$</TEX> and <TEX>$AUC_{insulin}$</TEX> values in NIDDM groups. Treatment with petroleum ether fraction produced a greater reduction in elevated glucose and <TEX>$AUC_{glucose}$</TEX> levels as compared to treatment with other fractions. Treatment with methanolic extract of Z. officinale and its fractions also produced significant reduction in the elevated lipid, serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) levels in NIDDM rats. The effect of petroleum ether fraction on elevated lipid, SGOT and SGPT levels was significantly greater as compared to treatment with other fractions. The concentration of 6-gingerol was found to be maximum in petroleum ether fraction (11.430%) and minimum in chloroform fraction (0.973%). The methanolic extract and toluene fraction was found to contain 3.080% and 2.191 %, 6-gingerol respectively. In conclusion, our data suggest that methonolic extract and its fractions possess significant antidiabetic activity in NIDDM rats. The extent of activity appears to be dependent on the concentration of 6-gingerol present in the extract or its fractions.

Effects of Callophyllis japonica powder on carbon tetrachloride-induced liver injury in rats

A limited number of studies have been conducted on the bioactivity of Callophyllis japonica (C. japonica), which is a red seaweed that is traditional in the oriental diet. In this report, the hepatoprotective effect of C. japonica was studied in a carbon tetrachloride hepatotoxicity model in rats. A single intraperitoneal injection of 1.25 ml/kg of 20% in olive oil produced an elevated level of serum glutamic pyruvic transaminase (SGPT) and increased enzyme activity of serum glutamic oxaloacetic transaminase (SGOT). Pre-treatment with C. japonica (150 mg/kg/d) for 3 days in rats reduced the levels of SGPT and SGOT compared with control levels (P injection in rats was ineffective at reducing SGPT and SGOT. The histopathological findings in each group largely agreed with the biochemical data. The results of this study support the suggestion that C. japonica has a hepatoprotective effect on chemical-induced liver injury.

Diagnostic Discordance for Hepatitis C Virus Infection in Hemodialysis Patients

Hepatitis C virus (HCV) infection is associated with an increase in proinflammatory cytokine levels. Similar changes are seen in maintenance hemodialysis patients with malnutrition-inflammation-cachexia syndrome (MICS), which is associated with poor clinical outcomes in this population. We hypothesized that HCV transcription-mediated amplification (TMA), a sensitive qualitative molecular test for HCV RNA, may identify maintenance hemodialysis patients with HCV infection not detected by means of antibody enzyme immunoassay (EIA), particularly in those with MICS. We evaluated HCV status in 314 maintenance hemodialysis patients by using HCV antibody EIA (version 2.0; Abbott Laboratories, Abbott Park, IL) and HCV TMA (Bayer Diagnostics Laboratories, Berkeley, CA). Twenty-five patients (8%) were EIA positive (EIA+)/TMA+; 4 patients (1%), EIA+/TMA negative (TMA-), and 22 patients (7%), EIA-/TMA+. In the 47 TMA+ patients, the sensitivity of EIA for HCV infection was only 53%. TMA+ patients had lower albumin levels and higher tumor necrosis factor alpha and serum glutamic oxaloacetic transaminase levels than TMA- patients. EIA+/TMA+ patients were more likely than EIA-/TMA+ or EIA-/TMA- patients to have hypoalbuminemia and higher iron and transaminase levels. Of all TMA+ patients, EIA- patients were more likely to have diabetes, be on dialysis therapy longer, and have lower liver enzyme levels and higher proinflammatory cytokine levels, including tumor necrosis factor alpha and interleukin 6. Maintenance hemodialysis patients infected with HCV according to TMA have clinical features suggestive of MICS. In this population, HCV EIA appears to have a low sensitivity for the identification of HCV infection, which may be caused by the confounding effect of MICS or other demographic or clinical factors. These apparently false-negative HCV antibody test results are seen in persons with a longer time on hemodialysis therapy, mirroring observations in other populations with serious progressive conditions, such as human immunodeficiency virus infection.

Effect of Achyranthes aspera on the immunity and survival of Labeo rohita infected with Aeromonas hydrophila

Achyranthes aspera seed was incorporated in the diets (at 0.01%, 0.1% and 0.5%) of Labeo rohita, rohu fingerlings (3.0 ± 0.4 g). After 2 weeks, the fish were immunized with heat-killed Aeromonas hydrophila, and after a further 2 weeks the rohu were experimentally infected with Aeromonas hydrophila (ATCC 49140). After 7 days blood and serum were sampled to determine superoxide anion production, bactericidal activity, lysozyme, serum protein, albumin, globulin, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and alkaline phosphatase (ALP). Superoxide anion production, serum bactericidal activity, lysozyme, ALP, serum protein, albumin:globulin ratio (A/G) were enhanced in Achyranthes treated groups compared to the control group. SGOT and SGPT levels were elevated in control group, but in Achyranthes treated groups the levels were similar to the uninfected-control group. Higher cumulative mortalities were observed in the control group (77%) up to day-9 after infection. This gradually decreased with increasing dose of Achyranthes, 66% mortality in 0.01% group, 57% mortality in 0.1% group and 28% mortality in 0.5% group. These results indicate that Achyranthes aspera stimulates immunity and increases resistance to infection in L. rohita.

Effect of giardia on some biochemical variables in human blood serum

The alteration in serum glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaline phosphotase (ALP) and total protein during giardiasis were studied.This study has been performed on 53 patients with giardiasis; the control consists of 22 children without giardiasis. The results of each group of patients were compared with the same age of the control, the results indicated that the level of serum GOT, GPT and ALP was significantly higher than that of control for each age , while the level of protein was significantly lower than that for control for each age group.The results indicate that the giardiasis affected the function of liver and the intestine, which lead to some biochemical changes in serum.

The Effect of Dimethyl Dimethoxy Biphenyl Dicarboxylate (DDB) against Tamoxifen-induced Liver Injury in Rats: DDB Use Is Curative or Protective

Tamoxifen citrate is an anti-estrogenic drug used for the treatment of breast cancer. It showed a degree of hepatic carcinogenesis, when it used for long term as it can decrease the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in liver rat cells leading to liver injury. In this study, a model of liver injury in female rats was done by intraperitoneal injection of tamoxifen in a dose of 45 mg/kg body weight for 7 successive days. This model produced a state of oxidative stress accompanied with liver injury as noticed by significant declines in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) in a dose of 200 mg/kg body weight daily for 10 successive days, resulted in alleviation of the oxidative stress status of tamoxifen-intoxicated liver injury in rats as observed by significant increments in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases; sGPT and sGOT levels. The administration of DDB before tamoxifen intoxication (as protection) is more little effective than its curative effect against tamoxifen-induced liver injury. The data obtained from this study speculated that DDB can mediate its biochemical effects through the enhancement of the antioxidant enzyme activities and reduced glutathione level as well as decreasing lipid peroxides.

The CD154-CD40 T-cell co-stimulation pathway in liver ischemia and reperfusion inflammatory responses.

Ischemia-reperfusion (I/R) injury is a prime antigen-independent inflammatory factor in the dysfunction of liver transplants. The precise contribution of T cells in the mechanism of I/R injury remains to be elucidated. As the CD154-CD40 co-stimulation pathway provides essential second signal in the initiation and maintenance of T-cell-dependent immune responses, this study was designed to assess the role of CD154 signaling in the pathophysiology of liver I/R injury. A mouse model of partial 90-min warm hepatic ischemia followed by 6 hr of reperfusion was used. Three animal groups were studied: (1) wild-type (WT) mice treated with Ad-(-gal versus Ad-CD40 immunoglobulin; (2) untreated WT versus CD154 (MR1) monoclonal antibody-treated WT mice; and (3) untreated WT versus CD154 knockout mice. The disruption of CD154 signaling in all three animal groups ameliorated otherwise fulminant liver injury, as evidenced by depressed serum glutamic oxaloacetic transaminase levels, compared with controls. These beneficial effects were accompanied by depressed hepatic T-cell sequestration, local decrease of vascular endothelial growth factor expression, inhibition of tumor necrosis factor-(and T-helper type 1 cytokine production, and induction of antiapoptotic (Bcl-2/Bcl-xl) but depression of proapoptotic (caspase-3) proteins. By using in parallel a gene therapy approach, pharmacologic blockade, and genetically targeted mice, these findings document the benefits of disrupting CD154 to selectively modulate inflammatory responses in liver I/R injury. This study reinforces the key role of CD154-CD40 T-cell co-stimulation in the pathophysiology of liver I/R injury.

Valproate‐induced Proximal Renal Tubular Dysfunction: Clinically Relevant in the Severely Disabled Epileptic Population

To the Editor: We read with interest the article by Knorr et al., Fanconi Syndrome Caused by Antiepileptic Therapy with Valproic Acid, Epilepsia 2004;45:868–71, and their observation that this severe proximal renal tubular dysfunction on literature review has occurred almost exclusively in mentally retarded, severely disabled, often wheelchair-bound children. As consultants to several developmental centers, we follow valproic acid (VPA)-treated epilepsy patients with profound mental retardation and other accompanying severe central nervous system disabilities. After observing a septicemic death associated with a reduction in serum albumin to 2.1 g/dl (3.4–5.0 g/dl, normal range) during VPA monotherapy, we systematically monitored these VPA-treated epilepsy patients and not uncommonly observed declining serum albumin levels to well below normal range. Of the first 12 patients (10 women, two men; ages, 16–50 years) so categorized, those supported with enteral nutrition (five of 12) who had weight increase, edema, and reduced serum albumin levels had no change in intake of calories and protein. Pearson correlations did not reveal a relation between the serum albumin levels and the protein intake. Plasma VPA concentrations were found to be within therapeutic range in the entire group, and none had a history of renal or hepatic disease. Serum glutamic oxaloacetic transaminase (SGOT) levels were within normal limits in 10 of 12, but ammonia levels were slightly elevated in seven of 12. The 24-h urine protein levels were found to be elevated, with a range of 115 to 2,850 mg, with a mean serum albumin level of 3.1 g/dl. The blood urea nitrogen (BUN) levels were all within normal limits. On discontinuance of VPA, the serum albumin levels increased to normal range (mean, 3.8 g/dl) within 2 to 3 weeks. We now routinely monitor VPA-treated patients at our developmental centers, discontinuing VPA when serum albumin levels decrease persistently to >2.8–3.0 g/dl, or even slightly higher levels if liver function appears to be problematic as well. Although the full-blown Fanconi syndrome appears rare, in our experience, a significant degree of proximal tubular dysfunction as a result of VPA toxicity with significant reductions in serum albumin is relatively common in this severely disabled epilepsy patient group, both children and adults, and requires systematic attention. Korinthenberg et al. (Renal tubular dysfunction following treatment with anti-epileptic drugs. Eur J Pediatr 1994;153:855–8) documented subclinical VPA (monotherapy)-induced proximal tubular dysfunction in otherwise healthy children with epilepsy. Therefore the superimposed loss of weight-bearing with its multiple endocrine/renal effects in our severely disabled epilepsy patient group could be the predisposing factor producing clinically significant VPA proximal renal tubular toxicity (Regnard et al. Validity of microgravity simulation models on earth. Am J Kidney Dis 2001;38:668–74).

Comparison of the metabolic effects of oral contraceptive and nonhormonal contraceptive use in women over 40 years old

The aim of this study was to compare metabolic changes during use of low-dose combined oral contraceptives (COCs) and those of nonhormonal contraceptives in perimenopausal women. Thirty-nine healthy women over 40 years old who attended the Family Planning Clinic of the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, were recruited, 20 in the COC group received COC preparations containing 30 μg of ethinyl estradiol and 150 μg of levonorgestrel and 19 in the nonhormonal group were intrauterine device users. Blood samples were taken upon admission and 6 months later. Minor biochemical changes associated with low-dose COC use included an increase in glucose tolerance, triglycerides, serum albumin, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels but a decrease in fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol, total bilirubin and alkaline phosphatase levels. There was no clinical significance for the metabolic changes. Low-dose COCs can be a satisfactory contraceptive choice for healthy perimenopausal women.

Heme oxygenase-1 alleviates ischemia/reperfusion injury in aged liver

To investigate if ischemia/reperfusion (I/R) injury in aged liver could be alleviated by heme oxygenase-1 (HO-1). Three groups of SD rats (16 mo old) were studied. Group 1: control donors received physiological saline 24 h before their livers were harvested; group 2: donors were pretreated with hemin 24 h before their livers were harvested; and group 3: donors received hemin 24 h before their livers were harvested and zinc protoporphyrin (ZnPP, HO-1 inhibitor) was given to recipients at reperfusion. The harvested livers were stored in University of Wisconsin solution (4 degrees) for 6 h, and then transplanted to syngeneic rats. Serum glutamic oxaloacetic transaminase (SGOT), apoptotic cells, and apoptotic gene were measured 3, 6, 12, 24, 48 h after reperfusion. We measured the apoptotic index by TUNEL, determined the expression of antiapoptotic Bcl-2 and proapoptotic (caspase-3) gene products by Western blot. After 3, 6, 12, 24, and 48 h of reperfusion, the SGOT levels (584.4+/-85.8 u/L, 999.2+/-125.2 u/L, 423.4+/-161.3 u/L, 257.8+/-95.8 u/L, and 122.4+/-26.4 u/L) in hemin group were significantly (all P<0.05) lower than those in saline group (1082.2+/-101.2 u/L, 1775.2+/-328.3 u/L, 840.4+/-137.8 u/L, 448.6+/-74.3 u/L, and 306.2+/-49.3 u/L). Liver HO-1 enzymatic activity correlated with beneficial effects of hemin and deleterious effects of adjunctive ZnPP treatment. Markedly less apoptotic (TUNEL+) liver cells 3, 6, 12, 24, and 48 h after reperfusion (5.16+/-0.73, 10.2+/-0.67, 9.28+/-0.78, 7.14+/-1.12, and 4.78+/-0.65) (P<0.05) could be detected in hemin liver grafts, as compared to controls (7.82+/-1.05, 15.94+/-1.82, 11.67+/-1.59, 8.28+/-1.09, and 6.36+/-0.67). We detected the increased levels of Bcl-2 (1.5-fold) expression and compared with saline controls. These differences were most pronounced at 12 h after transplantation. In contrast, an active form of proapoptotic caspase-3 (p20) protein was found to be 2.9-fold lower at 24 h in hemin-pretreated group, as compared to saline liver transplant controls. HO-1 overexpression can provide potent protection against cold I/R injury. This effect depends, at least in part, on HO-1-mediated inhibition of antiapoptotic mechanism.

Effect of &lt;i&gt;Abutilon indicum&lt;/i&gt; on Carbon Tetrachloride Induced Hepatic Damage in Albino Rats

Ethanolic extract of Abutilon indicum (Malvaceae) was screened for its hepatoprotective potential, using carbon tetra chloride induced hepatic damage model in rats. A dose of 400 mg / kg body weight was employed in the study. The effect was assessed by monitoring the serum levels of the following enzymes, like serum glutamate-oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP). Abutilon indicum significantly reduced serum levels of SGOT, SGPT, and SALP comparable with Liv-52 as a reference standard.