Membrane Stabilization and Detoxification of Acetaminophen-Mediated Oxidative Onslaughts in the Kidneys of Wistar Rats by Standardized Fraction of Zea mays L. (Poaceae), Stigma maydis.

This study evaluated membrane stabilization and detoxification potential of ethyl acetate fraction of Zea mays L., Stigma maydis in acetaminophen-induced oxidative onslaughts in the kidneys of Wistar rats. Nephrotoxic rats were orally pre- and posttreated with the fraction and vitamin C for 14 days. Kidney function, antioxidative and histological analyses were thereafter evaluated. The acetaminophen-mediated significant elevations in the serum concentrations of creatinine, urea, uric acid, sodium, potassium, and tissue levels of oxidized glutathione, protein-oxidized products, lipid peroxidized products, and fragmented DNA were dose-dependently assuaged in the fraction-treated animals. The fraction also markedly improved creatinine clearance rate, glutathione, and calcium concentrations as well as activities of superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase in the nephrotoxic rats. These improvements may be attributed to the antioxidative and membrane stabilization activities of the fraction. The observed effects compared favorably with that of vitamin C and are informative of the fraction's ability to prevent progression of renal pathological conditions and preserve kidney functions as evidently supported by the histological analysis. Although the effects were prominently exhibited in the fraction-pretreated groups, the overall data from the present findings suggest that the fraction could prevent or extenuate acetaminophen-mediated oxidative renal damage via fortification of antioxidant defense mechanisms.

Kinetics of α-amylase and α-glucosidase inhibitory potential of Zea mays Linnaeus (Poaceae), Stigma maydis aqueous extract: An in vitro assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Corn silk (Zea mays L., Stigma maydis) is an important herb used traditionally in many parts of the world to treat array of diseases including diabetes mellitus. Inhibitors of α-amylase and α-glucosidase offer an effective strategy to modulate levels of post prandial hyperglycaemia via control of starch metabolism. AIM OF THE STUDY: This study evaluated α-amylase and α-glucosidase inhibitory potentials of corn silk aqueous extract. Active principles and antioxidant attributes of the extract were also analysed. MATERIALS AND METHODS: The α-amylase inhibitory potential of the extract was investigated by reacting its different concentrations with α-amylase and starch solution, while α-glucosidase inhibition was determined by pre-incubating α-glucosidase with different concentrations of the extract followed by addition of p-nitrophenylglucopyranoside. The mode(s) of inhibition of the enzymes were determined using Lineweaver-Burke plot. RESULTS: In vitro analysis of the extract showed that it exhibited potent and moderate inhibitory potential against α-amylase and α-glucosidase, respectively. The inhibition was concentration-dependent with respective half-maximal inhibitory concentration (IC50) values of 5.89 and 0.93mg/mL. Phytochemical analyses revealed the presence of alkaloids, flavonoids, phenols, saponins, tannins and phytosterols as probable inhibitory constituents. Furthermore, the extract remarkably scavenges reactive oxygen species like DPPH and nitric oxide radicals, elicited good reducing power and a significant metal chelating attributes. CONCLUSION: Overall, the non-competitive and uncompetitive mechanism of action of corn silk extract is due to its inhibitory effects on α-amylase and α-glucosidase, respectively. Consequently, this will reduce the rate of starch hydrolysis, enhance palliated glucose levels, and thus, lending credence to hypoglycaemic candidature of corn silk.

Comparison of the effects of dietary plant sterol and stanol esters on lipid metabolism.

BACKGROUND AND AIM: To compare the cholesterol-lowering efficacy and other metabolic effects of plant sterol and stanol esters, both of which are commonly used in the dietary management of hypercholesterolaemia. METHODS AND RESULTS: The cholesterol-lowering efficacy of equivalent intakes of sterol and stanol esters and of different intakes of stanol esters were compared at 1 and 2 months, both in normal subjects and treated patients with familial hypercholesterolaemia. Systemic effects were assessed by measuring serum levels of plant sterols and of lathosterol and 7alpha-hydroxy-cholestenone, indices of sterol absorption and of cholesterol and bile acid synthesis respectively. There were no significant differences during the study between 1.6g daily of sterol and stanol esters in reducing total cholesterol (by 3-7%) or low density lipoprotein cholesterol (by 4-8%), nor between 1.6 and 2.6 g daily of stanol. However, the cholesterol-lowering effect of plant sterol esters was attenuated between 1 and 2 months. This was accompanied by increased serum plant sterols and decreased levels of 7alpha-hydroxy-cholestenone, especially in statin-treated hypercholesterolaemic patients not taking bile acid sequestrants. CONCLUSIONS: These findings suggest that absorption of dietary plant sterols suppressed bile acid synthesis, thereby diminishing their cholesterol-lowering efficacy. In contrast, plant stanols reduced plant sterol absorption and maintained their cholesterol-lowering efficacy.

Effect of a statin on hepatic apolipoprotein B-100 secretion and plasma campesterol levels in the metabolic syndrome.

OBJECTIVE: We aimed to study the effect of atorvastatin, a statin, on cholesterol synthesis and absorption and VLDL-apoB metabolism in obese men with the metabolic syndrome. METHODS: A total of 25 dyslipidaemic obese men were randomized to atorvastatin (n=13) (40 mg/day) or matching placebo (n=12) for 6 weeks. Hepatic secretion and fractional catabolic rate (FCR) of VLDL-apoB was measured using an intravenous bolus of d(3)-leucine before and after treatment. ApoB isotopic enrichment was measured using GCMS and multicompartmental modelling. Plasma lathosterol: cholesterol and campesterol:cholesterol ratios were determined to assess cholesterol synthesis and cholesterol absorption, respectively. RESULTS: Compared with placebo, atorvastatin significantly decreased (P<0.05) total cholesterol, triglyceride, LDL-cholesterol and VLDL-apoB. Plasma lathosterol:cholesterol ratio decreased from 26.4+/-2.4 to 8.8+/-0.8, while the campesterol:cholesterol ratio increased from 26.5+/-4.4 to 38.6+/-5.8 (P<0.01). Atorvastatin also increased VLDL-apoB FCR from 3.82+/-0.33 to 6.30+/-0.75 pools/day (P<0.01), but did not significantly alter VLDL-apoB secretion (12.8+/-1.7 to 13.8+/-2.0 mg/kg/day). CONCLUSIONS: In obesity, atorvastatin inhibits cholesterogenesis but increases intestinal cholesterol absorption. The increased cholesterol absorption may counteract the inhibitory effect on hepatic VLDL-apoB secretion, but it does not apparently influence enhanced catabolism of VLDL-apoB.

Treatment with atorvastatin alters the ratio of interleukin-12/interleukin-10 gene expression [corrected].

BACKGROUND: Statins have been shown to have pleiotropic effects extending beyond their ability to lower cholesterol. MATERIAL AND METHODS: Seventeen patients with heterozygous familial hypercholesterolaemia participated in a single-blind placebo controlled study. The patients underwent three treatment regimens: placebo (4 weeks), atorvastatin 10 mg day(-1) (4 weeks) and atorvastatin 40 mg day(-1) (12 weeks). Following each treatment period, serum lipids and plasma mevalonic acid were measured, mononuclear leukocytes were isolated and total RNA was prepared. The content of mRNA for IL-12p35 and IL-10 was assayed, blinded, by real-time quantitative polymerase chain reactions. RESULTS: Treatment of the subjects with atorvastatin decreased the abundance of IL-12p35 mRNA in mononuclear cells, but did not alter that of IL-10, so that the ratio of the IL-12p35 to IL-10 mRNA content was significantly reduced (P < 0.0026). The IL-12p35/IL-10 ratio correlated significantly with plasma mevalonic acid concentrations but not with serum LDL concentrations. CONCLUSIONS: This study provides evidence that atorvastatin exerts an immunomodulatory effect in vivo, characterized by a decrease in the ratio of IL-12 mRNA to IL-10 mRNA in leukocytes. The immunomodulatory effect of statins, in addition to their cholesterol-lowering properties, may contribute to the rapid cardiovascular benefit observed during treatment with statins and reduced the rate of rejection in patients with solid organ transplantation.

Determinants of variable response to statin treatment in patients with refractory familial hypercholesterolemia.

Interindividual variability in low density lipoprotein (LDL) cholesterol (LDL-C) response during treatment with statins is well documented but poorly understood. To investigate potential metabolic and genetic determinants of statin responsiveness, 19 patients with refractory heterozygous familial hypercholesterolemia were sequentially treated with placebo, atorvastatin (10 mg/d), bile acid sequestrant, and the 2 combined, each for 4 weeks. Levels of LDL-C, mevalonic acid (MVA), 7-alpha-OH-4-cholesten-3-one, and leukocyte LDL receptor and hydroxymethylglutaryl coenzyme A reductase mRNA were determined after each treatment period. Atorvastatin (10 mg/d) reduced LDL-C by an overall mean of 32.5%. Above-average responders (LDL-C -39.5%) had higher basal MVA levels (34.4+/-6.1 micromol/L) than did below-average responders (LDL-C -23.6%, P<0.02; basal MVA 26.3+/-6.1 micromol/L, P<0.01). Fewer good responders compared with the poor responders had an apolipoprotein E4 allele (3 of 11 versus 6 of 8, respectively; P<0.05). There were no baseline differences between them in 7-alpha-OH-4-cholesten-3-one, hydroxymethylglutaryl coenzyme A reductase mRNA, or LDL receptor mRNA, but the latter increased in the good responders on combination therapy (P<0.05). Severe mutations were not more common in poor than in good responders. We conclude that poor responders to statins have a low basal rate of cholesterol synthesis that may be secondary to a genetically determined increase in cholesterol absorption, possibly mediated by apolipoprotein E4. If so, statin responsiveness could be enhanced by reducing dietary cholesterol intake or inhibiting absorption.

Müllerian Inhibiting Substance lowers testosterone in luteinizing hormone-stimulated rodents.

Müllerian Inhibiting Substance (MIS) expression is inversely proportional to the serum concentration of testosterone in males after birth and in vitro studies have shown that MIS can lower testosterone production by Leydig cells. Also, mice overexpressing MIS exhibited Leydig cell hypoplasia and lower levels of serum testosterone, but it is not clear whether this is a result of MIS affecting the development of Leydig cells or their capacity to produce testosterone. To examine the hypothesis that MIS treatment will result in decreased testosterone production by mature Leydig cells in vivo, we treated luteinizing hormone (LH)-stimulated adult male rats and mice with MIS and demonstrated that it can lead to a several-fold reduction in testosterone in serum and in testicular extracts. There was also a slight decrease in 17-OH-progesterone compared to the more significant decrease in testosterone, suggesting that MIS might be regulating the lyase activity of cytochrome P450c17 hydroxylase/lyase (Cyp17), but not its hydroxylase activity. Northern analysis showed that, in both MIS-treated rats and mice, the mRNA for Cyp17, which catalyzes the committed step in androgen synthesis, was down-regulated. In rats, the mRNA for cytochrome P450 side-chain cleavage (P450scc) was also down-regulated by MIS. This was not observed in mice, indicating that there might be species-specific regulation by MIS of the enzymes involved in the testosterone biosynthetic pathway. Our results show that MIS can be used in vivo to lower testosterone production by mature rodent Leydig cells and suggest that MIS-mediated down-regulation of the expression of Cyp17, and perhaps P450scc, contributes to that effect.

Effect of inhibiting HMG-CoA reductase on 7 alpha-hydroxy-4-cholesten-3-one, a marker of bile acid synthesis: contrasting findings in patients with and without prior up-regulation of the latter pathway.

BACKGROUND: Atorvastatin is a potent inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, but its effect on bile acid synthesis is unknown. The objectives of the study were to determine the effect of atorvastatin on bile acid synthesis in patients in whom this process had not been or had been previously up-regulated by pharmacological or surgical means. MATERIALS AND METHODS: Four patients with heterozygous familial hypercholesterolaemia (FH) and partial ileal bypass (PIB) and 19 FH heterozygotes without PIB were treated with placebo, atorvastatin 10 mg and atorvastatin 40 mg daily, each regimen for 4 weeks. The non-PIB group was subsequently treated with bile acid (BA) sequestrant 8-16 g daily followed by co-administration of atorvastatin 10 mg, each for 4 weeks. Plasma 7 alpha-hydroxy-4-cholesten-3-one (7 alpha-HCO), a well-validated marker of BA synthesis was measured using high-performance liquid chromatography with UV detection. RESULTS: The plasma 7 alpha-HCO concentration was tenfold higher with placebo in the PIB than in the non-PIB group (418.5 ng mL-1 vs. 39.6 ng mL-1 p = 0.0001). Levels decreased in PIB patients treated with atorvastatin 10 mg and 40 mg daily (350.1 ng mL-1 and 174.0 ng mL-1, P = 0.007 respectively) but did not change significantly in the non-PIB group (44.7 ng mL-1 and 28.3 ng mL-1 respectively). Administration of BA sequestrant to non-PIB patients increased 7 alpha-HCO to 197.4 ng mL-1; this decreased to 106.0 ng mL-1 during co-administration of atorvastatin 10 mg daily (P = 0.0001). CONCLUSION: Atorvastatin decreases the rate of BA synthesis only if the latter is up-regulated by PIB or BA sequestrants, presumably by limiting the supply of newly synthesized free cholesterol.

Modification of the carbohydrate composition of sulfite pulp by purified and characterized beta-xylanase and beta-xylosidase of Aureobasidium pullulans.

Both beta-xylanase and beta-xylosidase were purified to homogeneity from a xylose-grown culture of Aureobasidium pullulans. Cellular distribution studies of enzyme activities revealed that beta-xylanase was an extracellular enzyme, during both the exponential and stationary phases, whereas beta-xylosidase was mostly periplasmic associated. The beta-xylanase exhibited very high specificity for xylan extracted from Eucalyptus grandis dissolving pulp, whereas the beta-xylosidase was only active on p-nitrophenyl xyloside and xylobiose. Comparison of kcat/Km ratios showed that the beta-xylanase hydrolyzed xylan from dissolving pulp 1.3, 2.1, and 2. 3 times more efficiently than Eucalyptus hemicellulose B, Eucalyptus hemicellulose A, and larchwood xylan, respectively. The beta-xylosidase exhibited a transxylosylation reaction during the hydrolysis of xylobiose. When applied on acid sulfite pulp, both enzymes released xylose and hydrolyzed xylan to a different extent. Although beta-xylosidase (0.4 U/g pulp) liberated more xylose from pulp than beta-xylanase (4.7 U/g pulp), it was responsible for only 3% of xylan solubilization. Treatment of pulp with beta-xylanase liberated 51.7 microgram of xylose/g and hydrolyzed 10% of xylan. The two enzymes acted additively on pulp and removed 12% of pulp xylan. A synergistic effect in terms of release of xylose from pulp was observed when the enzyme mixture of beta-xylanase and beta-xylosidase was supplemented with beta-mannanase. However, this did not result in further enzymatic degradation of pulp xylan. Both beta-xylanase and beta-xylosidase altered the carbohydrate composition of sulfite pulp by increasing the relative cellulose content at the expense of reduced hemicellulose content of pulp.

Rapid and simple assay for feruloyl and p-coumaroyl esterases.

A rapid, simple and sensitive method for detection of ferulic and p-coumaric acids using HPLC has been developed which can be used to determine the respective phenolic acid esterase activities of microorganisms. Prior concentration, purification or derivatization of the samples are not required. As little as 0.5 mg ferulic or p-coumaric acid/I could be detected and estimated in < 1 h. The method is specific for the two phenolic acids sice no interference by other components was observed.