Effect of the Zinc Oxide Nanoparticles and Thiamine for the Management of Diabetes in Alloxan-Induced Mice: a Stereological and Biochemical Study

This research was carried out to evaluate the antidiabetic effects of zinc oxide nanoparticles (ZnO NPs) and thiamine following experimental diabetes. Fifty-six 6-week-old female mice were used and divided into seven groups of eight animals. Diabetes was induced in fasted mice by using intraperitoneal (IP) injection of alloxan (180 mg/kg). Groups included (I) non-diabetic control, (II) thiamine (30 mg/l, IP), (III) alloxan-induced diabetic mice, (IV) diabetes + ZnO NPs (0.1 mg/kg IP), (V) diabetes + ZnO NPs (0.5 mg/kg IP), (VI) diabetes + ZnO NPs (0.1 mg/kg IP) + thiamine (30 mg/l, IP), and (VII) diabetes + ZnO NPs (0.5 mg/kg IP) + thiamine (30 mg/l, IP). Coincident with pancreas recovery, in diabetic treated mice (groups IV to VII), the mean islet volume, islets per square micrometer, and volume density of the pancreas had increased than in alloxan-induced diabetic mice. ZnO NPs and thiamine induced a decreasing blood glucose, lower serum triglyceride (TG), LDL, and total cholesterol (TC) levels in alloxan-induced diabetic mice treated with ZnO NPs and thiamine, simultaneously increasing HDL as well. In conclusion, ZnO NPs and thiamine are potent antidiabetic factors, and that, these compound supplementation possesses hypoglycemic properties and have effect on serum lipid parameters in diabetes mice.     

Effects of Iscador and Vincristine and 5-Fluorouracil on Brain, Liver, and Kidney Element Levels in Alloxan-Induced Diabetic Mice

Exposure to substance toxicity is especially dangerous for diabetics because it accelerates and intensifies diabetic complication. Homeostasis of trace elements can be disrupted by diabetes mellitus. On the other hand, disturbance in trace element status in diabetes mellitus may contribute to insulin resistance and development of diabetic complications. The aim of the present study was to compare the concentration of elements in the brain, liver, and kidneys of animals with induced diabetes after the administration of plant preparations (iscador and vincristine) and 5-fluorouracil. The experiments were carried out on male mice. The animals were divided into five groups of ten mice each: one control and four experimental groups. The first experimental group was administered alloxan at 75 mg/kg b.w. for 4 days, the second group was administered both alloxan at 75 mg/kg b.w. and vincristine 1 mg/kg b.w. for 4 days, and the third group was administered both alloxan at 75 mg/kg b.w. and 5-fluorouracil 75 mg/kg b.w. for 4 days. The animals of the fourth group were administered both alloxan at 75 mg/kg b.w. and iscador Qu at 5 mg/kg b.w. for 4 days. Calcium, magnesium, iron, copper, zinc, sodium, and potassium levels in the tissues were analyzed by flame atomic absorption spectrophotometer. We observed that zinc, copper, magnesium, sodium, and potassium were lower in the brain as compared to the control animals. The copper levels in the liver were also lower in diabetic groups than in control groups. However, the iscador and vincristine and 5-fluorouracil did not induce significant differences in the five groups. In conclusion, results of the current study indicated that changes of the investigated essential elements may contribute to explaining the role of impaired element metabolism of some elements in the progression of diabetic complications.     

Effect of treatment of cow’s urine “Gomutra” and antioxidants in alleviating the lindane-induced oxidative stress in kidney of Swiss mice (Mus musculus)

The study aimed to evaluate the effect of cow urine and combination of antioxidants against lindane induced oxidative stress in Swiss mice. Male healthy mice, 8–10 weeks old, weighing 30 ± 5 g were randomly selected and divided into eight groups, namely, control (C); lindane (L); antioxidant (A), antioxidant+lindane (A+L), cow urine (U), cow urine+lindane (U+L), cow urine+antioxidants (U+A) and cow urine+antioxidants+lindane (U+A+L). Group C animals were administered only the vehicle (olive oil); doses selected for other treatments were: lindane: 40 mg/kg b.w.; antioxidants: 125 mg/kg b.w. (vitamin C: 50 mg/kg b.w., vitamin E: 50 mg/kg b.w., α-lipoic acid: 25 mg/kg b.w.) and cow urine: 0.25 ml/kg b.w. In group A+L and U+L antioxidants and cow urine were administered 1 h prior to lindane administration and in group U+A and U+A+L cow urine was administered 10 min before antioxidants. All treatments were administered orally continuously for 60 days. Lindane treated group showed increased lipid peroxidation, whereas glutathione, glutathione peroxidase, superoxide dismutase, catalase, protein and endogenous levels of vitamin C and E were significantly decreased compared to control. Administration of cow urine and antioxidants alleviated the levels of these biochemical parameters.     

Terminalia pallida fruit ethanolic extract ameliorates lipids,lipoproteins, lipid metabolism marker enzymes and paraoxonase in isoproterenol-induced myocardial infarcted rats

The present study aimed to evaluate the effect of Terminalia pallida fruit ethanolic extract (TpFE) on lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase (PON) in isoproterenol (ISO)-induced myocardial infarcted rats. PON is an excellent serum antioxidant enzyme which involves in the protection of low density lipoprotein cholesterol (LDL-C) from the process of oxidation for the prevention of cardiovascular diseases. ISO caused a significant increase in the concentration of total cholesterol, triglycerides, LDL-C, very low density lipoprotein cholesterol and lipid peroxidation whereas significant decrease in the concentration of high density lipoprotein cholesterol. ISO administration also significantly decreased the activities of lecithin cholesterol acyl transferase, PON and lipoprotein lipase whereas significantly increased the activity of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase. Oral pretreatment of TpFE at doses 100, 300 and 500?mg/kg body weight (bw) and gallic acid (15?mg/kg bw) for 30?days challenged with concurrent injection of ISO (85?mg/kg bw) on 29th and 30th day significantly attenuated these alterations and restored the levels of lipids, lipoproteins and the activities of lipid metabolizing enzymes. Also TpFE significantly elevated the serum antioxidant enzyme PON. This is the first report revealed that pretreatment with TPFE ameliorated lipid metabolic marker enzymes and increased the antioxidant PON in ISO treated male albino Wistar rats.     

Effect of Lycopene Application in Rats with Experimental Diabetes Using Lipoprotein, Paraoxonase and Cytokines

This study was conducted with the purpose of researching the effect of lycopene application on lipoprotein, paraoxonase (PON) and cytokines that are projected to be used in the diagnosis and treatment of diabetes by making experimental diabetes. At the end of a 1-month trial period, under ether anesthesia with jelly tubes, blood samples were taken from rat hearts. Blood samples were centrifuged and serum was obtained. From the serum samples, HbA_1c, paraoxonase activity, lipoprotein levels and cytokines were determined. HbA_1c levels and PON activity were found to be p < 0.001. At the triglyceride level, with regard to the control group, in all the groups a significant rise occurred (p ≤ 0.001). At the cholesterol level, with regard to the control group, a decline was observed in the other groups (p < 0.05). At the VLDL level, with regard to the control group, a significant rise was observed in the other groups (p < 0.05). At the HDL (p < 0.001) and LDL (p < 0.05) levels, with regard to the control group, a significant decline was observed in the other groups. At the TNF-α, IL-2, IL-6 and IL-10 levels no difference was found (p > 0.05). Experimental diabetes models have an important place in analyzing diabetes complications and determining treatment approaches.     

Prevention of cardiotoxicity of aflatoxin B1 via dietary supplementation of papaya fruit extracts in rats

The aim of the current study was to evaluate the cardioprotective ability of water (WE) and ethanolic (EE) papaya fruits extracts against cardiotoxicity induced by aflatoxin B₁ (AFB₁) in rats. Forty two female Sprague–Dawley rats were divided into six treatment groups and treated orally for 2 weeks as follow: control group, the group treated with WE (250 mg/kg b.w), the group treated with EE (250 mg/kg b.w), the group treated orally with AFB₁ (17 μg/kg b.w) and the groups treated orally with AFB₁ plus WE or EE. The results indicated that treatment with AFB₁ resulted in oxidative stress in the heart manifested by the marked increase in cardiac malondialdehyde and calcium levels accompanied with a significant decrease in cardiac total antioxidant capacity. Serum nitric oxide and sodium levels, lactate dehydrogenase and creatine kinase isoenzyme activities were significantly increased, whereas, cardiac Na⁺/K⁺-ATPase activity and serum potassium were insignificantly affected. Supplementation with WE or EE effectively ameliorated most of the changes induced by AFB₁. It could be concluded that both extracts attenuated the oxidative stress induced in heart tissue by AFB₁ and WE was more pronounced due to the higher total phenolic contents than in the EE.     

Bilirubin clearance and antioxidant activities of ethanol extract of Phyllanthus amarus root in phenylhydrazine-induced neonatal jaundice in mice

The ability of ethanol extract of Phyllanthus amarus root (EEPA) to decrease bilirubin level and oxidative stress in phenylhydrazine-induced neonatal jaundice in mice was investigated. Administration of phenylhydrazine (75 mg/kg b.w.) significantly elevated total and unconjugated serum bilirubin level compared to control mice. EEPA (5, 10, and 20 mg/kg b.w., oral) dose-dependently reduced the bilirubin level. EEPA treatment also upregulated hepatic CAR and CYP3A1, accounting for its ability to facilitate bilirubin clearance. A single dose of EEPA (20 mg/kg b.w.) induced higher level of bilirubin clearance than phototherapy, widely used for treating neonatal jaundice. Furthermore, phenylhydrazine administration significantly increased MDA, protein carbonyl, and total thiol content and lowered the GSH level along with superoxide dismutase and catalase activity in erythrocyte compared to the control group. Single administration of EEPA (20 mg/kg b.w.) significantly reversed the trend. Presence of gallic acid, gentisic acid, and ortho-coumaric acid in EEPA was identified by HPLC analysis. Amongst these, the major phenolic constituent, gallic acid, exhibited significant bilirubin-lowering effect. These results suggested that P. amarus may be beneficial in reducing bilirubin level as well as oxidative stress in neonatal jaundice.     

Antihypercholesterolemic and antioxidative effects of an extract of the oyster mushroom, Pleurotus ostreatus, and its major constituent, chrysin, in Triton WR-1339-induced hypercholesterolemic rats

Hypercholesterolemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. In the present study, an attempt was made to evaluate the putative antihypercholesterolemic and antioxidative effects of an ethanolic extract of the oyster mushroom (Pleurotus ostreatus) and chrysin, one of its major components, in hypercholesterolemic rats. Hypercholesterolemia was induced in rats by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg body weight (b.wt.)), which resulted in persistently elevated blood/serum levels of glucose, lipid profile parameters (total cholesterol, triglycerides, low-density lipoprotein-, and very low-density lipoprotein-cholesterol), and of hepatic marker enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase). In addition, lowered mean activities of hepatic antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) and lowered mean levels of nonenzymatic antioxidants (reduced glutathione, vitamin C, and vitamin E) were observed. Oral administration of the mushroom extract (500 mg/kg b.wt.) and chrysin (200 mg/kg b.wt.) to hypercholesterolemic rats for 7 days resulted in a significant decrease in mean blood/serum levels of glucose, lipid profile parameters, and hepatic marker enzymes and a concomitant increase in enzymatic and nonenzymatic antioxidant parameters. The hypercholesterolemia-ameliorating effect was more pronounced in chrysin-treated rats than in extract-treated rats, being almost as effective as that of the standard lipid-lowering drug, lovastatin (10 mg/kg b.wt.). These results suggest that chrysin, a major component of the oyster mushroom extract, may protect against the hypercholesterolemia and elevated serum hepatic marker enzyme levels induced in rats injected with Triton WR-1339.     

The protective effect of misoprostol against doxorubicin induced liver injury

ABSTRACT

We investigated the potential hepatoprotective effects of misoprostol (MP) on doxorubicin (DOX) induced liver injury in rats using histology and biochemistry. We used 21 male Sprague-Dawley rats divided randomly into three groups: group 1, control; group 2, DOX; group 3, DOX + MP. The control group was injected intraperitoneally (i.p.) with 0.5 ml 0.9% w/v NaCl and given 1 ml 0.9% NaCl orally for 6 days. DOX was administered i.p. as a single dose of 20 mg/kg. MP, 0.2 mg/kg, was given orally for 6 days. Treatment with MP increased high density lipoprotein cholesterol levels and decreased serum alanine aminotransferase, aspartate aminotransferase, low density lipoprotein cholesterol, triglycerides and total cholesterol levels significantly in serum. Increased malondialdehyde level and decreased catalase, glutathione and superoxide dismutase levels caused by DOX were suppressed significantly in liver tissue by MP. DOX + MP reduced loss of body weight. Oxidative stress was decreased, antioxidant activity was increased and histopathological changes were reduced in the DOX + MP group compared to the DOX group. Liver injury caused by DOX was attenuated by MP treatment owing to the antioxidative and anti-apoptotic effects of MP, which might be useful for reducing the severity of DOX induced liver injury.     

Impact on lipoprotein profile after long-term testosterone replacement in hypogonadal men.

Testosterone serum levels may influence the lipoprotein metabolism and possibly atherogenic risk. Our aim was to investigate the effects of long-term testosterone supplementation in hypogonadal men on multiple lipoprotein markers. 18 Hypogonadal men were studied before and after 3, 6, and 18 (n = 7) months of treatment with testosterone enanthate. During treatment, serum testosterone and estradiol increased, reaching normal levels (p < 0.0001 and 0.003, respectively). This was associated with a decrease in HDL cholesterol (from 1.40 +/- 0.10 mmol/l to 1.22 +/- 0.08 mmol/l, p < 0.001) after six months at the expense of HDL2 cholesterol (p < 0.01), as well as apoprotein A1 (from 139 +/- 3.4 mg/dl to 126 +/- 3.0 mg/dl, p < 0.005). Hepatic lipase activity increased (p < 0.05) and correlated positively with testosterone (r = 0.56, p < 0.02) and negatively with HDL cholesterol (r = - 0.58, p < 0.02). Total and LDL cholesterol, triglycerides, and apoprotein B did not increase. Among the seven patients who completed 18 months of treatment, triglycerides, total cholesterol, LDL and HDL cholesterol, as well as total cholesterol/HDL cholesterol ratio values did not differ from baseline while apoprotein A1 (p < 0.03) and HDL cholesterol (p < 0.015) remained decreased and hepatic lipase unchanged. Restoration of testosterone levels in hypogonadal men in this study did not reveal unfavorable changes based on total cholesterol/HDL cholesterol and LDL cholesterol/apoprotein B ratios, which are both atherogenic risk markers. Whether the changes in light of lipoprotein metabolism will adversely influence cardiovascular risk over time remains to be determined.     

Investigation of in vitro and in vivo antioxidant potential of secoisolariciresinol diglucoside

The present study was designed to evaluate the in vitro and in vivo ameliorative antioxidant potential of secoisolariciresinol diglucoside (SDG). In vitro antioxidant activity of synthetic SDG was carried out using DPPH, reducing power potency, and DNA protection assays. Wistar albino rats weighing 180–220 g were used for in vivo studies and liver damage was induced in the experimental animals by a single intraperitoneal (I.P.) injection of CCl₄ (2 g/kg b.w.). Intoxicated animals were treated orally with synthetic SDG at (12.5 and 25 mg/kg b.w.) and Silymarin (25 mg/kg) for 14 consecutive days. The levels of catalase (CAT), superoxide dismutase (SOD), peroxidase (POX), and lipid peroxidase (LPO) were measured in liver and kidney homogenates. The synthetic SDG exerts high in vitro antioxidant potency as it could scavenge DPPH at a IC₅₀ value of 78.9 μg/ml and has dose-dependent reducing power potency and protected DNA at 0.5 mg/ml concentration. Oral administration of synthetic SDG at 12.5 and 25 mg/kg b.w. showed significant protection compared to Silymarin (25 mg/kg) and the activities of CAT, SOD, and POX were markedly increased (P < 0.05), whereas LPO significantly decreased (P < 0.001) in a dose-dependent manner in liver and kidney in both pre- and post-treatment groups when compared to toxin-treated group. The results of in vitro and in vivo investigations revealed that synthetic SDG at 25 mg/kg b.w. is associated with beneficial changes in hepatic enzyme activities and thereby plays a key role in the prevention of oxidative damage in immunologic system.     

Ameliorating effect of eugenol on hyperglycemia by attenuating the key enzymes of glucose metabolism in streptozotocin-induced diabetic rats

Epidemiological studies have demonstrated that diabetes mellitus is a serious health burden for both governments and healthcare providers. This study was hypothesized to evaluate the antihyperglycemic potential of eugenol by determine the activities of key enzymes of glucose metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced into male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg body weight (b.w.)). Eugenol was administered to diabetic rats intragastrically at 2.5, 5, and 10 mg/kg b.w. for 30 days. The dose 10 mg/kg b.w. significantly reduced the levels of blood glucose and glycosylated hemoglobin (HbA1c) and increased plasma insulin level. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and liver marker enzymes (AST, ALT, and ALP), creatine kinase and blood urea nitrogen in serum and blood of diabetic rats were significantly reverted to near normal levels by the administration of eugenol. Further, eugenol administration to diabetic rats improved body weight and hepatic glycogen content demonstrated the antihyperglycemic potential of eugenol in diabetic rats. The present findings suggest that eugenol can potentially ameliorate key enzymes of glucose metabolism in experimental diabetes, and it is sensible to broaden the scale of use of eugenol in a trial to alleviate the adverse effects of diabetes.     

Effects of caloric restriction and gender on rat serum paraoxonase 1 activity

Paraoxonase 1 (PON1) associates to specific high-density lipoproteins (HDLs)--those containing apolipoprotein A-I (apoA-I) and apolipoprotein J (apoJ)--and is largely responsible for their antiatherogenic properties. Caloric restriction (CR) has been shown to reduce major atherosclerotic risk factors. The aims of this work were to study PON1 activity response to CR (40% over 14 weeks) and to elucidate whether there are adaptive differences related to gender. Serum and liver paraoxonase and arylesterase activities, serum triglyceride, total and HDL cholesterol concentrations, serum PON1, apoA-I and apoJ contents and liver PON1 mRNA levels were measured. No effects of CR or gender were observed in triglyceride, total cholesterol concentration and PON1 mRNA levels. HDL cholesterol was higher in female rats than in male rats and increased with CR only in the latter animals. Serum PON1 activities tended to be higher in female rats and dropped with CR, with females showing the biggest decrease. Serum PON1 content was higher in female rats and decreased in both genders with CR, whereas apoA-I and apoJ contents, which were higher in female rats too, decreased only in the former animals, accounting for the high PON1 activity decrease observed in these animals. In conclusion, the short-term CR-associated reduction of serum PON1 activity and PON1, apoA-I and apoJ levels points toward a reduced stability of HDL-PON1 complexes and/or HDL particle levels responsible for PON1 transport and function in the blood. Moreover, the variations in PON1 activity and apolipoprotein levels show gender-related differences that are indicative of a different adaptive strategy of male and female rats when faced with a period of food restriction.     

Simvastatin and vitamin E effects on cardiac and hepatic oxidative stress in rats fed on high fat diet

High fat diet (HFD) is a common cause of metabolic syndrome and type 2 diabetes mellitus. Published data showed that HFD and subsequent dyslipidemia are major triggers for oxidative stress. Forty-eight male Sprague–Dawley rats, weighing 170–200 g, were divided into six groups: control, control with vitamin E (100 mg/kg/day, i.p.), control with simvastatin (SIM) (10 mg/kg of body weight/day), HFD, HFD with vitamin E, and HFD with SIM. Standard and high cholesterol diets were given for 15 weeks and SIM and vitamin E were added in the last 4 weeks. In all rats, serum vitamin E, total cholesterol (TC), triglycerides (TG), low (LDL) and high (HDL) density lipoproteins, alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) as well as cardiac and hepatic thiobarbituric acid-reactive substances (TBARS) and antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) were measured. Also, electrocardiogram (ECG) was recorded. HFD significantly increased QTc interval, heart rate (HR), serum TC, TG, LDL, ALT, AST, ALP, GGT, liver TG, and cardiac and hepatic TBARS but decreased antioxidants and HDL, while SIM decreased HR, liver TG, serum TC, TG, and LDL and increased HDL in HFD rats. Vitamin E had no effect. Moreover, SIM and vitamin E decreased QTc interval, serum ALT, AST, ALP, GGT, and cardiac and hepatic TBARS and increased antioxidants in HFD rats. Histopathological observations confirm the biochemical parameters. SIM and vitamin E slow progression of hypercholesterolemia-induced oxidative stress in liver and heart and improve their functions.     

Effects of Dietary Supplementation of Zinc Oxide and Zinc Methionine on Layer Performance,Egg Quality,and Blood Serum Indices

The objective of this study was to evaluate the effectiveness of dietary zinc oxide (ZnO) and zinc methionine (Zn-Met) supplementation on layer performance, quality of egg, some blood constituents, and oxidative status in blood of laying hens. A total of 120 laying hens (Hisex Brown) 22-week-old were indiscriminately allotted into five groups of 24 hens with six replications (four birds/replicate). A complete randomized design experiment was performed including control (basal diet), two levels of ZnO (50 and 100 mg/kg basal diet), and two levels of Zn-Met (50 and 100 mg/kg basal diet) through 22 to 34 weeks of age. Supplementation of 100 mg of Zn-Met significantly (P = 0.001) increased feed intake compared to other treatment groups. The groups supplemented with 50 mg of ZnO and 100 mg of Zn-Met reported the significantly higher egg production rate (P = 0.002) and egg mass (P < 0.001) compared to other treated groups. All traits of egg quality were not statistically (P < 0.05 or 0.01) affected by ZnO or Zn-Met supplementation except shell thickness, Haugh unit score, and yolk to albumin ratio. Dietary supplementation of either ZnO or Zn-Met did not affect the oxidative parameters in serum except the activity of Cu-Zn-SOD. Serum triglyceride, total cholesterol, and LDL cholesterol (low-density lipoprotein) were significantly (P < 0.05) affected by Zn supplementation, while HDL cholesterol (high-density lipoprotein) did not affect. Compared to the control group, supplementation of ZnO or Zn-Met increased serum content of zinc with no differences among supplemental zinc doses. It could be concluded that dietary inorganic (ZnO) and organic (Zn-Met) supplemented up to 50 and 100 mg/kg, respectively, can be used as effective supplements to improve productivity of laying hens, serum zinc level, lipid profile (triglyceride and LDL cholesterol), and activity of Cu-Zn-SOD.     

Serum paraoxonase level and paraoxonase polymorphism in patients with acromegaly

Background: Acromegalic patients have increased cardiometabolic risk factors due to an elevation of growth hormone (GH) levels. Human serum paraoxonase (PON), a high-density lipoprotein (HDL)-related enzyme, is one of the major bioscavengers and decreases the oxidation of low-density lipoprotein (LDL), a key regulator in the pathogenesis of atherosclerosis. In this study, we investigated a potential relationship between serum PON levels or PON polymorphisms and acromegaly.

Methods: A total of 48 acromegalic patients and 44 healthy controls were included in this study. Serum GH levels, insulin-like growth factor-1 levels and lipid profiles were measured. Serum PON levels, as well as PON 1 L55M and Q192R gene polymorphisms, were examined.

Results: No significant differences were found in terms of age, gender, presence of diabetes, serum LDL cholesterol (LDL-C), HDL-C, or triglyceride levels between the case and control groups (P?>?0.05). A statistically significant difference was found in serum PON levels between the cases and controls (P?=?0.007). The median serum PON level was 101?±?63.36?U/l in the case group and 63?±?60.50?U/l in the control group. There was a significant correlation between serum PON levels and IGF-1 levels (P?=?0.004, r?=?0.319); however, no significant differences were found in PON1 L55M and PON Q192R polymorphisms between the patients and controls (P?=?0.607 and P?=?0.308, respectively). In addition, no significant differences were found in serum PON levels in acromegalic patients who were and were not in remission (P?=?0.385), nor between those with PON1 L55M and Q192R polymorphisms (P?=?0.161 and P?=?0.336, respectively).

Conclusions: Elevated serum PON levels were detected in acromegalic patients, independently of their remission status. This suggests protective effects for cardiometabolic risk parameters.     

VLDL triglycerides inhibit HDL-associated paraoxonase 1 (PON1) activity: in vitro and in vivo studies

We analyzed, for the first time, both in vitro and in vivo, the effect of very low density lipoprotein (VLDL), or of pure triglycerides, on high-density lipoprotein (HDL)-associated paraoxonase1 (PON1) catalytic activities. Incubation of serum or HDL from healthy subjects with VLDL (0-330 μg protein/mL) significantly decreased serum PON1 lactonase or arylesterase activities by up to 11% or 24%, and HDL-associated PON1 lactonase or arylesterase activities by up to 32% or 46%, respectively, in a VLDL dose-dependent manner. VLDL (0-660μg protein/mL) also inhibited recombinant PON1 (rePON1) lactonase or arylesterase activities by up to 20% or 42%, respectively. Similar inhibitory effect was noted upon rePON1 incubation with pure triglyceride emulsion. Bezafibrate therapy to three hypertriglyceridemic patients (400 mg/day, for one month) significantly decreased serum triglyceride concentration by 67%, and increased serum HDL cholesterol levels by 48%. PON1 arylesterase or paraoxonase activities in the patients' HDL fractions after drug therapy were significantly increased by 86-88%, as compared to PON1 activities before treatment. Similarly, HDL-PON1 protein levels significantly increased after bezafibrate therapy. Finally, bezafibrate therapy improved HDL biological activity, as HDL obtained after drug therapy showed increased ability to induce cholesterol efflux from J774A.1 macrophages, by 19%, as compared to HDL derived before therapy. We thus conclude that VLDL triglycerides inhibit PON1 catalytic activities, and bezafibrate therapy significantly improved HDL-PON1 catalytic and biological activities. ? 2012 International Union of Biochemistry and Molecular Biology, Inc.     

Diet-induced weight loss in overweight or obese women and changes in high-density lipoprotein levels and function

Diet-induced weight loss in women may be associated with decreases not only in plasma levels of low-density lipoprotein cholesterol (LDL-C), but also in high-density lipoprotein cholesterol (HDL-C). Whether a decrease in HDL-C is associated with altered HDL function is unknown. One hundred overweight or obese women (age 46 ± 11 years, 60 black; 12 diabetic) were enrolled in the 6-month program of reduced fat and total energy diet and low-intensity exercise. Serum cholesterol efflux capacity was measured in (3)H-cholesterol-labeled BHK cells expressing ABCA1, ABCG1, or SR-B1 transporters and incubated with 1% apolipoprotein B (apoB)-depleted serum. Antioxidant properties of HDL were estimated by paraoxonase-1 (PON1) activity and oxygen radical absorbance capacity (ORAC). Endothelial nitric oxide synthase (eNOS) activation was measured by conversion of L-arginine to L-citrulline in endothelial cells incubated with HDL from 49 subjects. Participants achieved an average weight loss of 2.2 ± 3.9 kg (P < 0.001), associated with reductions in both LDL-C (-6 ± 21 mg/dl, P = 0.004) and HDL-C (-3 ± 9 mg/dl, P = 0.016). Cholesterol efflux capacity by the ABCA1 transporter decreased by 10% (P = 0.006); efflux capacities by the ABCG1 and SR-B1 transporters were not significantly altered. ORAC decreased by 15% (P = 0.018); neither PON1 activity nor eNOS activation was significantly altered by reduction in HDL-C. Findings were similar for diabetic and nondiabetic subjects. Diet-induced weight loss in overweight or obese women is associated with a decrease in HDL-C levels, but overall HDL function is relatively spared, suggesting that decrease in HDL-C in this setting is not deleterious to cardiovascular risk.     

Serum Paraoxonase and Arylesterase Activities and Oxidative Stress Levels in Patients with SSRI Intoxication

Oxidative stress is a critical route of damage in various psychological stress-induced disorders, such as depression. Paraoxonase-1 (PON1) plays an important role as an endogenous free-radical scavenging molecule. The aim of this study was to evaluate the influence of serum PON1 activity and oxidative stress in patients with selective serotonin reuptake inhibitor (SSRI) intoxication. A total of 11 patients with SSRI intoxication and 20 healthy controls were enrolled. The serum total antioxidant capacity (TAC) and malondialdehyde (MDA) levels, as well as the paraoxonase and arylesterase activities, were measured spectrophotometrically. The serum TAC levels and the paraoxonase and arylesterase activities were significantly lower (for all, p < 0.001), whereas the serum MDA levels were significantly higher in the patients with SSRI intoxication than in the controls (p < 0.001). These results indicated that decreased PON1 activity and increased oxidative stress represent alternative mechanisms in SSRI toxicity. More studies are needed to elucidate the role of PON1 activity in the etiology of SSRI intoxication.     

Does dietary magnesium modulate blood lipids?

In a randomized, single-blind, controlled study (400 patients aged 25-63 yr; 374 males, 26 females), 206 subjects were administered a magnesium-rich diet, and 194 subjects their usual diet, for 6 wk. Age, sex, body weight, hypertension, hyperlipidemia, smoking, obesity, diuretic therapy, and diabetes were comparable between the two groups, as were laboratory data at entry to the study. Intervention-group A received a significantly higher amount of dietary magnesium and potassium compared to group B, which received its usual diet. After 6 wk, there was a significant fall in total serum cholesterol (228.5 +/- 46.2 mg/dL), LDL cholesterol 146.5 +/- 75.5 mg/dL), and triglyceride (143.8 +/- 40.5 mg/dL) in group A compared to serum cholesterol (242.5 +/- 58.2 mg/dL), LDL cholesterol (157.0 +/- 78.4 mg/dL), and triglyceride (156.5 +/- 60.0 mg/dL) at entry to study, but no such changes in group-B subjects. HDL cholesterol showed a marginal mean decrease of 0.8 mg/dL in group B and a 2.5 mg/dL increase in group A. The changes in blood lipids were consistent with an increased intake of magnesium and with a rise in serum levels. Although a general blood-lipid-reducing effect of such a diet cannot be excluded, it is possible that dietary magnesium may have contributed to the reduction of total serum cholesterol, LDL cholesterol, and triglyceride, and the marginal rise in HDL cholesterol. More studies with longer follow-up periods are needed to confirm this observation.