Reduction in maternal serum values of glucose and gamma-glutamyltransferase after supplementation with alpha-lipoic acid in women with gestational diabetes mellitus.

AIM: Alpha-lipoic acid (ALA) is a short chain fatty acid which has a key role in energy production. ALA is also known as a universal antioxidant. The aim of the present study was to explore the effects of ALA supplementation in women with gestational diabetes mellitus. METHODS: A randomized double-blind placebo-controlled clinical trial study was designed. Women with gestational diabetes mellitus (n = 60) during 24-28 weeks of gestation were selected and divided randomly into drug (n = 30) and placebo (n = 30) groups. Drug group supplemented with ALA (100 mg/day) for 8 weeks. The biochemical markers were measured before and after the intervention and considered significant at a P-value less than 0.05. RESULTS: Maternal circulating values of fasting blood sugar (P < 0.001), gamma-glutamyltransferase (P < 0.001) and alanine transaminase (P = 0.031) were decreased in the drug group after the intervention. However, values of urea, creatinine, uric acid, aspartate transaminase and alkaline phosphatase were not changed significantly after the trial. CONCLUSION: The present study has shown that supplementation with 100 mg/day of ALA had some beneficial effects on glucose metabolism and liver function in women with gestational diabetes mellitus.

The protective effect of thymoquinone over olanzapine-induced side effects in liver, and metabolic side effects.

OBJECTIVES: The aim of the study was to investigate the possible protective qualities of thymoquinone (TQ) against the side-effects of olanzapine (OLZ) in an experimental model in rat liver with histologic and biochemical assessments. METHODS: Experimental procedures were performed on 35 female Sprague Dawley rats. Rats were randomly divided into five groups as: group 1: control; group 2: OLZ; group 3: OLZ+TQ-1; group 4: OLZ+TQ-2; and group 5: OLZ+TQ-3. RESULTS: The results showed that a 2­week administration of OLZ (4 mg/kg, once a day for the first week, 8 mg/kg once a day for the second week, p.o.) and treatment with TQ (25, 50, 100 mg/kg, once daily, p.o.) significantly reduced weight gain induced by OLZ. In addition, TQ increased the total antioxidant status (TAS), high-density lipoprotein cholesterol (HDL), insulin levels and decreased serum oxidative stress index (OSI), total oxidant status (TOS), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), low density lipoprotein cholesterol (LDL), glucose, triglycerides (TG) and total cholesterol (CH) levels significantly (p < 0.05). CONCLUSION: This study revealed that treatment with TQ might protect liver tissue against the side-effects of OLZ. TQ could be an effective course of therapy to enhance therapeutic efficacy (Tab. 4, Fig. 4, Ref. 47).

Allopurinol prevents cardiac and skeletal muscle damage in professional soccer players.

Xanthine oxidase (XO), a free radical-generating enzyme, is involved in tissue damage produced during exhaustive exercise. Our aim was to test whether allopurinol, a powerful inhibitor of XO, may be effective in preventing exercise-induced tissue damage in soccer players. Twelve soccer players were randomized into two experimental groups. One received allopurinol, before a match of the premier Spanish Football League, and the other placebo. Allopurinol prevented the exercise-induced increase in all the markers of skeletal muscle damage analyzed: creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and myoglobin. Creatine kinase-MB isoenzyme and highly sensitive troponin T, specific biomarkers of myocardial injury, increased significantly in the placebo but not in the allopurinol-treated group after the football match. We also found that the exercise-induced lipid peroxidation, as reflected by malondialdehyde measurements, was prevented after allopurinol administration. However, inhibition of XO did not prevent the increment in the activity of alanine aminotransferase found after the match. No changes in the serum gamma glutamyltransferase activity was found after the match on either the placebo and the allopurinol groups. These two enzymes were determined as biomarkers of liver injury. Allopurinol represents an effective and inexpensive pharmacological agent to prevent tissue damage in soccer players.

Strontium fructose 1, 6-diphosphate alleviate cyclophosphamide-induced oligozoospermia by improving antioxidant and inhibiting testicular apoptosis via FAS/FASL pathway.

This study investigated the treatment effects of a new compound, strontium fructose 1, 6-diphosphate (FDP-Sr), in cyclophosphamide (CP)-induced oligozoospermia. FDP-Sr, with extra high-energy supply, could reverse male hypogonadism in the testis. Male Wistar rats were randomly divided into three groups: control group (vehicle treated), CP group and CP + FDP-Sr group. Both CP group and CP + FDP-Sr groups were orally administered CP (20 mg kg(-1) ) consecutively for the first 7 days to establish CP-induced testicular toxic models. Subsequently, CP group was given orally distilled water per day, whereas CP + FDP-Sr group was received FDP-Sr (200 mg kg(-1) ) for 49 days. Compared to the CP group, the FDP-Sr group showed significantly increased levels of serum testosterone, testis relative weights and epididymal sperm counts in rats. In addition, rats treated by FDP-Sr showed the recuperative activities of testicular marker enzymes and normalised levels of antioxidants in tissue. Testicular protection of FDP-Sr was further demonstrated by enhancing expression of P450scc, reducing ability of FAS/FASL and generating cytoprotection in the histopathological study. FDP-Sr appeared to possess an ability to attenuate CP-induced reproduction toxicity via the activation of antioxidants and steroidogenesis enzymes, and alleviate oligozoospermia via inhibition of testicular apoptosis by FAS/FASL pathway.

[Additional advantages of mexicor used in combined therapy of coronary heat disease and diabetes mellitus of 2nd type].

This open prospective randomized 16-week study of combined therapy of coronary heat disease (CHD) and and diabetes mellitus of 2nd type (DM2) with secondary non-alcoholic fatty liver disease (NAFLD) including mexicor was designed to estimate structural and functional liver characteristics. Mexicor was shown to act as a hepatoprotector reducing the frequency of cytolithic syndrome when used together with statins in combined therapy of atherogenic dyslipidemia. It also significantly decreased the number of patients with elevated levels of gamma-glutamyltranspeptidase. These changes suggest favourable prognosis for patients with CHD and DM2 because enhanced activity of this enzyme is believed to be a predictor of high cardiovascular risk. Mexicor promoted combined hypolipidemic effect, reduced the degree of insulin resistance, improved hepatic metabolism, and lowered cardiovascular risks in patients with CHD and DM2.

A case series of concomitant treatment of perhexiline with amiodarone.

BACKGROUND: Concomitant treatment with amiodarone and perhsexiline has been considered to be relatively contraindicated because of the hypothetical risk of potentiated adverse effects mediated by additive inhibition of carnitine palmitoyl transferase 1. AIM: To study the prevalence of adverse effects associated with the concomitant use of perhexiline and amiodarone. METHODS: A retrospective analysis of a single hospital database of patients receiving perhexiline and amiodarone between July 2009 and April 2011. Files were reviewed for short- and long-term adverse effects requiring drug cessation. Glucose concentration, gamma glutamyl transferase activity. and perhexiline blood concentrations were recorded. RESULTS: We identified 26 patients concomitantly treated with perhexiline and amiodarone, 20 on a long-term basis. In 6 cases, amiodarone was introduced on top of preceding perhexiline. In none of the cases were drugs stopped because of adverse effects. Although blood glucose concentrations fell significantly 48 hours postadmission to hospital, this seems to reflect the resolution of "admission hyperglycemia" rather than onset of hypoglycemia; the latter was rare (5 patients), mild, and clinically silent. In 4 patients, gamma glutamyl transferase approximately doubled. CONCLUSIONS: Traditionally, concomitant treatment with amiodarone and perhexiline has been considered to be relatively contraindicated on the basis of the theoretical potential for synergistic toxicity. This cohort of 26 patients received this concomitant treatment without any excess of major adverse reactions. Our findings suggest that concomitant treatment with perhexiline and amiodarone may be safe in the setting of (1) previous tolerance of either agent, and (2) titration of plasma perhexiline concentrations to guide therapy.

Plasma level of atherogenic and anti-atherogenic factors among palm wine drinkers of rural southwest Nigeria.

BACKGROUND: Scientific evidence indicates that light to moderate drinking on a daily basis may significantly reduce the risks of coronary heart disease (CHD). In contrast, excessive alcohol intake and binge drinking are toxic to both the heart and overall health. There is dearth of knowledge whether palm wine exhibit any these properties. OBJECTIVES: The objective of this study is to evaluate the effect of level of palm wine consumption on the plasma atherogenic and anti-atherogenic factors among the rural dwellers. METHODS AND MATERIALS: Fifty-eight male volunteers between the ages of 28-69 yrs were recruited. They were divided into two groups; 28 moderate drinkers with intake of 20-70 grams/day and 30 heavy drinker with intake of >70 grams/day of palm wine at a sitting for 3 to 4days per week with a minimum duration of 5 years. Thirty controls of the same age groups with the same socioeconomic status were recruited. Plasma activities of liver enzymes, plasma concentration of Total Cholesterol (TC), Triglyceride (TG), High-Density Lipoprotein (HDL), Low-Density Lipoproteins (LDL) and apolipoprotiens (ApoA1 & Apo B) were determined. TC/HDL, LDL/HDL and ApoB/A1 ratios calculated. RESULTS: There was significant increase in plasma concentration of TG, LDL, ApoB and decrease in HDL and ApoA 1 among heavy drinkers. However, there was an increase in plasma level of ApoA1 and decrease in ApoB among moderate drinkers but not significant when compared to the controls. A positive correlation were observed between level of palm wine consumption (>70gram/day) and plasma levels of TG LDL, ApoB, TC/HDL ratio, ApoB/ApoA1 ratio; but negative correlation with HDL and ApoA1. CONCLUSION: Our finding revealed that heavy consumption of palm wine may promote atherogenic factors, but the benefits of moderate consumption recorded need further investigations. There is also the need to determine the level of polyphenolic substances if any in palm wine.

Deteriorating effect of fluvastatin on the cholestatic liver injury induced by bile duct ligation in rats.

Antiinflammatory effect of statins mediated by the reduction of cytokine IL-6 in hepatocytes have been reported. Contrary to beneficial effect, statins can increase susceptibility to mitochondrial dysfunction. Extrahepatic biliary obstruction is associated with oxidative stress, pro-inflammatory response and hepatocyte mitochondrial dysfunction. The aim of our study was to verify the effect of fluvastatin on cholestatic liver injury. Cholestasis was induced in Wistar rats by bile duct ligation. Fluvastatin (1 or 5 mg/kg) was administered after surgery and then daily for 7 days. The dose of 5 mg/kg led to the deterioration of hepatocellular injury. Despite lower production of IL-6, decrease in GSH content, rise of TGFß and inhibition of respiratory complex I in mitochondria were determined. The mRNA expressions of canalicular transporter Mdr1b and basolateral transporter Mrp3 increased in cholestatic liver. Fluvastatin administration then led to the attenuation of this change. Analogously, mRNA expression of conjugative enzyme Ugt1a1 was diminished by fluvastatin administration to cholestatic rats. We can conclude that decrease in the antioxidative status and mitochondrial dysfunction could at least in part participate on the deteriorating effect of fluvastatin. Whether these processes can be a consequence of the alteration in metabolism and transport of potentially toxic substances remains to verify.

Antioxidant properties of Amaranthus hypochondriacus seeds and their effect on the liver of alcohol-treated rats.

Amaranth constitutes a valuable pseudocereal, due to its nutritional quality and its nutraceutical properties, which contribute to improve human health. This work evaluated the effect of a diet based on Amaranthus hypochondriacus (Ah) seed on oxidative stress and antioxidant status in the liver of rats sub-chronically exposed to ethanol. The seed extract was investigated for antioxidant capacity in vitro, showing an adequate content of total phenols and antioxidant activity elevated. For in vivo assays, four groups of six rats each were fed with an AIN-93 M diet for 28 days. In groups III and IV casein was replaced by Ah as the protein source; groups II and IV were received ethanol in the drinking water (20% v/v). When comparing groups IV and II, the following was observed: significant decrease in the activity of aspartate aminotransferase and content of malondialdehyde (p<0.001) in serum; decrease of malondialdehyde and increase in the activity and gene expression of Cu,Zn-superoxide dismutase, also, decrease in the NADPH oxidase transcript levels (p<0.05) in liver. Our data suggest that Ah is a good source of total phenols and exerts a protective effect in serum and in liver of rats intoxicated with ethanol.

Alcohol, metabolic risk and elevated serum gamma-glutamyl transferase (GGT) in Indigenous Australians.

BACKGROUND: The interaction between overweight/obesity and alcohol intake on liver enzyme concentrations have been demonstrated. No studies have yet examined the interaction between metabolic syndrome or multiple metabolic risk factors and alcohol intake on liver enzymes. The aim of this study was to examine if alcohol consumption modifies the effect of metabolic risk on elevated serum GGT in Indigenous Australians. METHODS: Data were from N = 2609 Indigenous Australians who participated in a health screening program in rural far north Queensland in 1999-2000 (44.5% response rate). The individual and interactive effects of metabolic risk and alcohol drinking on elevated serum GGT concentrations (>or=50 U/L) were analyzed using logistic regression. RESULTS: Overall, 26% of the population had GGT>or=50 U/L. Elevated GGT was associated with alcohol drinking (moderate drinking: OR 2.3 [95%CI 1.6 - 3.2]; risky drinking: OR 6.0 [4.4 - 8.2]), and with abdominal obesity (OR 3.7 [2.5 - 5.6]), adverse metabolic risk cluster profile (OR 3.4 [2.6 - 4.3]) and metabolic syndrome (OR 2.7 [2.1 - 3.5]) after adjustment for age, sex, ethnicity, smoking, physical activity and BMI. The associations of obesity and metabolic syndrome with elevated GGT were similar across alcohol drinking strata, but the association of an adverse metabolic risk cluster profile with elevated GGT was larger in risky drinkers (OR 4.9 [3.7 - 6.7]) than in moderate drinkers (OR 2.8 [1.6 - 4.9]) and abstainers (OR 1.6 [0.9 - 2.8]). CONCLUSIONS: In this Indigenous population, an adverse metabolic profile conferred three times the risk of elevated GGT in risky drinkers compared with abstainers, independent of sex and ethnicity. Community interventions need to target both determinants of the population's metabolic status and alcohol consumption to reduce the risk of elevated GGT.

The effect of melatonin supplementation on liver indices in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized clinical trials.

Several randomized clinical trials (RCTs) evaluated the effect of melatonin supplementation on liver enzymes in patients with non-alcoholic fatty liver disease (NAFLD) and reported conflicting results. To meet these discrepancies, a meta-analysis was conducted to evaluate the eff ;ect of melatonin on liver indices in patients with NAFLD. To collect the required data, a thorough search was conducted through Web of science, Pubmed, Cochrane database, Embase, Google Scholar, ProQuest, and Scopus databases. The aim was to find clinical trials over the effect of melatonin supplementation on liver indices up to 16 May 2019. As a result, five eligible articles were selected and analysed in this meta-analysis using a fixed-effects model. Heterogeneity test was performed by I2 statistics and Cochrane Q test. The results showed that melatonin had a significant effect on aspartate aminoteransferase (AST) (WMD = 2.29, [95 %CI: 1.14, 3.43] IU/L, p = <0.001), alkaline phosphatase (ALP) (WMD = -8.40, [95 %CI -11.33, -5.48] IU/L, p < 0.001), and gamma-glutamyltransferase (GGT) (WMD = -33.37, [95 %CI: -37.24, -29.49] IU/L, p= < 0.001). Melatonin had no significant effect on alanine aminotransferase (ALT) regarding the overall effect size. Based on this meta-analysis, melatonin supplementation can improve liver indices. However, more RCTs are required with larger sample sizes and better control of confounding variables such as weight, body mass index, and gender to determine the effect of melatonin on patients with non-alcoholic fatty acid disease.

Atorvastatin associated with gamma glutamyl transpeptidase elevation in a hyperlipidemia patient: A case report and literature review.

RATIONALE: Atorvastatin is the most common drug used in therapy for cardiovascular diseases. The most common adverse side effects associated with statins are myopathy and hypertransaminasemia. Here, we report a rare case of gamma glutamyl transpeptidase (GGT) elevation induced by atorvastatin. PATIENT CONCERNS: A 47-year-old male was admitted to our hospital with dyslipidemia, he had been taking pitavastatin 2 mg/day for 2 months. The levels of total cholesterol (265.28 mg/dL) and low-density lipoprotein-cholesterol (LDL) (179.15 mg/dL) were also high. DIAGNOSIS: Blood lipid test showed mixed dyslipidemia. INTERVENTION: Atorvastatin 10 mg/day was given to the patient. OUTCOMES: The patient came back to our hospital for blood tests after 4 weeks. Although no symptoms were detectable, the patient's GGT level was markedly elevated (up to 6-fold over normal level) with less marked increases in alkaline phosphatase (ALP) and alanine aminotransferase (ALT). The serum GGT level returned to normal within 6 weeks of cessation of atorvastatin. LESSONS: This is a case of GGT elevation without hyperbilirubinemia, hypertransaminasemiam, or serum creatine phosphokinase (CPK) abnormalities despite an atorvastatin regimen. This case highlights GGT elevation caused by atorvastatin, a rare but serious condition. Clinicians should be aware of these possible adverse effects and monitor liver function tests in patients on statin therapy.

Benefits and harms of ginseng supplementation on liver function? A systematic review and meta-analysis.

OBJECTIVE: Existing evidence on the possible effects of ginseng on liver function has not been fully established. Therefore, the present review was undertaken to evaluate the overall effects of ginseng supplementation on liver enzymes in adults. METHODS: A systematic computerized literature search of PubMed, Scopus, Web of Science, Cochrane Library and Google scholar databases was conducted up to May 2019. All RCTs using ginseng supplements in adults were included in this systematic review and meta-analysis. RESULTS: Overall, 14 randomized trials (with 20 arms) including 992 subjects were identified. Pooled analysis did not illustrate any significant changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and albumin (ALB) levels, however, it showed a minor significant increase in bilirubin (BIL) levels. Subgroup analysis by dosage and study population revealed significant increase of bilirubin after ginseng supplementation ≥3 g/day or in unhealthy individuals. CONCLUSION: Ginseng appears to have neither hepatoprotective nor hepatotoxic effects in conventional doses and duration. It is noteworthy that this seems applicable only for individuals with healthy liver function. Further largescale studies are warranted to confirm present findings.

Effect of L-Carnitine Supplementation on Liver Enzymes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND AIM: Possible Hepato-protective effects of L-carnitine have been reported in previous studies. Present study was conducted to systematically review the efficacy of L-carnitine supplementation on liver enzymes. METHODS: The following databases were searched up to December 2018: PubMed, Scopus, ISI Web of Science, and the Cochrane library. Only randomized controlled trials (RCTs) evaluating the effects of L-carnitine supplementation on liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) were included. Pooled effect size measured using random effect model (Dersimonian-Liard). RESULTS: A total of 16 studies (including 1025 participants) were included in the present meta-analysis. Pooled analysis indicated that L-carnitine supplementation significantly decreased ALT (weighted mean difference (WMD): -10.729 IU/L, 95% CI: -13.787, -7.672, p <0.001; I2 = 95.9%), AST (WMD: -7.149 IU/L, 95% CI: -9.202, -5.096, p <0.001; I2 = 93.5%) and GGT (WMD: -7.395: IU/L, 95% CI: -9.171, -5.619, p <0.001; I2 = 80.1%). Subgroup analysis revealed that effect of L-carnitine supplementation on liver enzymes was not significant in normal weight and healthy subjects. Baseline BMI and health status were the potential source of heterogeneity. CONCLUSION: L-carnitine supplementation showed beneficial hepato-protective effects on circulating liver enzymes.

Potassium dichromate-induced changes on urinary-specific activities of gamma-glutamyl transpeptidase and alanine aminopeptidase enzymes.

It has been reported that potassium dichromate-induced nephrotoxicity is evidenced by diminution in creatinine clearance, increase in urinary protein, and structural damage to the proximal tubules. Damage to tissue often leads to the release of enzymes from the injured cells into the extracellular fluids. The aim of this study was to establish whether potassium dichromate induces changes in the urinary-specific activities of gamma-glutamyl transpeptidase and alanine aminopeptidase enzymes. Our results show that the administration of a single intraperitoneal dose of potassium dichromate decreased the activity of such enzymes in urine.

Effects of Coenzyme Q10 Supplementation on Serum Values of Gamma-glutamyl transferase, Pseudocholinesterase, Bilirubin, Ferritin, and High-Sensitivity C-Reactive Protein in Women with Type 2 Diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a disease associated with increased oxidative stress which results from mitochondrial dysfunction. Coenzyme Q10 (CoQ10) is an essential antioxidant for energy production in mitochondria. The purpose of this randomized double-blind clinical trial study was to evaluate the effects of CoQ10 supplementation on serum values of gamma-glutamyl transferase (GGT), pseudocholinesterase (PchE), bilirubin, ferritin, and high-sensitivity c-reactive protein (hs-CRP) and metabolic syndrome biomarkers in women with T2DM. MATERIAL & METHODS: Eighty women with T2DM enrolled in this study. Thirty six of them were randomized in the drug group (receiving 100 mg/day of CoQ10) and 44 women were randomized in placebo group. Intervention was continued for 12 weeks. In both groups 35 subjects finished the study and were included in the analysis. Serum levels of the variables were measured before and after supplementation. RESULTS: Serum values of FBS (P=0.039), HOMA-IR (P=0.01), ferritin (P<0.001), total cholesterol (TC) (P=0.006), LDL-C (P=0.007) decreased and HDL-C (P=0.02) increased significantly in the drug group after intervention. Serum levels of triglyceride (P=0.09) decreased marginally in CoQ10 group. CONCLUSIONS: The results of the current study had shown that after supplementation with 100 mg/day of CoQ10 for 12 weeks, serum values of FBS, HOMA-IR, TC, LDL-C and ferritin were decreased and values of HDL-C were increased in women with T2DM.

Evaluation of the use of tacrolimus ointment for the prevention of hypertrophic scars in experimental model.

BACKGROUND: Tacrolimus, for its activity on modulation of collagen production and fibroblast activity, may have a role in the prevention of hypertrophic scars. OBJECTIVES: Evaluate macroscopic, microscopic, metabolic, laboratory effects and side effects of the use of topical tacrolimus ointment, in different concentrations, in the prevention of hypertrophic scars. METHODS: Twenty-two rabbits were submitted to the excision of 2 fragments of 1 cm of each ear, 4 cm apart, down to cartilage. The left ear of the animals was standardized as control and Vaseline applied twice a day. The right ear received tacrolimus ointment, at concentrations of 0.1% on the upper wound and 0.03% on the lower wound, also applied twice a day. Macroscopic, microscopic, laboratory criteria and the animals' weight were evaluated after 30 days of the experiment. RESULTS: Wounds treated with tacrolimus, at concentrations of 0.1% and 0.03%, when compared to control, showed a lower average degree of thickening (p = 0.048 and p <0.001, respectively). The average of scar thickness and lymphocyte, neutrophil and eosinophil concentrations are lower in the treated wounds compared to the control (p <0.001, p=0.022, p=0.007, p=0.044, respectively). The mean concentration of lymphocytes is lower in wounds treated with a higher concentration of the drug (p=0.01). STUDY LIMITATIONS: experiment lasted only 30 days. CONCLUSIONS: Tacrolimus at the 2 concentrations evaluated reduced the severity of inflammatory changes and positively altered the macroscopic aspect of the scar in the short term. Its use was shown to be safe, with no evidence of systemic or local adverse effects.

Glutathione regulation in arsenic-induced porcine aortic endothelial cells.

The objective was to investigate the regulation of glutathione (GSH) turnover in porcine aortic endothelial cells (PAECs) treated with sodium arsenite (NaAsO(2)), arsenic trioxide (As(2)O(3)) or sodium arsenate (Na(2)HAsO(4)) up to 72 hr at 0, 1, 5, and 10 microM, respectively. Intracellular GSH and glutathione disulfide (GSSG) contents, as well as the activities and mRNA levels of glutamate-cysteine lyase (GCL; gamma-glutamylcysteine synthetase) and gamma-glutamyl transpeptidase (GGT), were examined. The trivalent arsenic compounds increased GSH and GSSG contents in PAECs. An increase in GCL activity was observed at 24hr whereas an increase in GCL mRNA level was observed at 72 hr. The increase in GGT activity was only observed at 72 hr. In addition, a tendency of increase in GGT mRNA level was observed. Na(2)HAsO(4) treatment did not affect GSH content and the turnover-related enzymes. A differential GSH modulation in PAECs by trivalent arsenic compounds was found. The regulatory mechanism responsible for the As(2)O(3)-induced GSH increase is related to the GSH-turnover enzymes, GCL and GGT, while that for the NaAsO(2)-induced GSH increase may not be related to expression of GSH-turnover enzymes.

Effects of oral administration of aqueous extract of Fadogia agrestis (Schweinf. Ex Hiern) stem on some testicular function indices of male rats.

AIM OF THE STUDY: The effects of administration of aqueous extract of Fadogia agrestis (Schweinf. Ex Hiern) stem on some testicular function indices of male rats (Rattus norvegicus) and their recovery potentials for 10 days were investigated. MATERIALS AND METHODS: Rats were grouped into four: A, B, C and D where A (the control) received orally 1 ml of distilled water (the vehicle), B, C and D (the test groups) received orally on daily basis graded doses of 18, 50 and 100mg/kg body weight of the plant extract, respectively, for 28 days. RESULTS: Compared with the control, extract administration for 28 days at all the doses resulted in significant increase (P<0.05) in percentage testes-body weight ratio, testicular cholesterol, sialic acid, glycogen, acid phosphatase and gamma-glutamyl transferase activities while there was significant decrease (P<0.05) in the activities of testicular alkaline phosphatase, acid phosphatase, glutamate dehydrogenase and concentrations of protein. Recoveries were made by the animals on some of the testicular function indices mainly at 18 mg/kg body weight. CONCLUSIONS: The alterations brought about by the aqueous extract of Fadogia agrestis stem are indications of adverse effects on the male rat testicular function and this may adversely affect the functional capacities of the testes. The recovery made at the dose of 18 mg/kg body weight as used in folklore medicine suggests that it does not exhibit permanent toxicity at this dose.

Carnitine deficiency provokes cisplatin-induced hepatotoxicity in rats.

This study investigates whether or not carnitine deficiency is a risk factor and could contribute to cisplatin-induced liver toxicity. A total of 60 adult male Wistar albino rats were divided into six groups. The first three groups were injected intraperitoneally with normal saline, propionyl-l-carnitine (500 mg/kg), and d-carnitine (500 mg/kg), respectively, for 10 successive days. The fourth, fifth and sixth groups were injected intraperitoneally with the same doses of normal saline, propionyl-l-carnitine and d-carnitine, respectively, for 5 successive days before and after a single dose of cisplatin (7 mg/kg). Administration of the standard nephrotoxic dose of cisplatin did not produce any changes in serum alanine transaminase and gamma-glutamyl transferase and no morphological changes in liver tissues. However, it did produce a significant increase in thiobarbituric acid reactive substances and total nitrate/nitrite and a significant decrease in reduced glutathione content in liver tissues. On the other hand, combined treatment with cisplatin and d-carnitine induced a dramatic increase in serum alanine transaminase and gamma-glutamyl transferase, as well as progressive reduction in total carnitine and ATP content in liver tissue. Moreover, histopathological examination of liver tissues confirmed the biochemical data, where cisplatin and d-carnitine combination showed signs of liver injury manifested as focal necro-inflammatory changes and portal inflammation. Interestingly, in carnitine supplemented rats using propionyl-l-carnitine, cisplatin did not produce any biochemical and histopathological changes in liver tissues. In conclusion, data from this study suggest for the first time that (1) carnitine deficiency is a risk factor and could precipitate cisplatin-induced hepatotoxicity, (2) oxidative stress is not the main cause of cisplatin-related hepatotoxicity and (3) propionyl-l-carnitine prevents the development of cisplatin-induced liver injury.