Aluminium-induced deterioration in reproductive performance and seminal plasma biochemistry of male rabbits: protective role of ascorbic acid

Aluminium (Al) has been proposed as an environmental factor that may contribute to some diseases, affect several enzymes and other biomolecules and induced free radical-mediated cytotoxicity. Also, Al induced reproductive toxicity and exerted a significant adverse effect on the steroidogenesis. The antioxidant ascorbic acid (AA) plays an important role in various physiological processes in the body including detoxification of different toxic materials. Therefore, the present investigation aimed to elucidate possible protective effects of AA in alleviating the toxicity of aluminium chloride (AlCl3) on reproductive performance, lipid peroxidation and enzyme activities in seminal plasma of male New Zealand white rabbits. Six rabbits per group were assigned to one of four treatment groups: 0 mg AA and 0 mg AlCl3 /kg body weight (BW) (control); 40 mg AA/kg BW; 34 mg AlCl3 /kg BW; 34 mg AlCl3 plus 40 mg AA/kg BW. Rabbits were orally administered their respective doses every other day for 16 weeks. Results obtained showed that AlCl3 significantly (P<0.05) decreased libido (by increasing the reaction time), ejaculate volume, sperm concentration, total sperm output, sperm motility (%), total motile sperm per ejaculate (TMS), packed sperm volume (PSV), total functional sperm fraction (TFSF), normal and live sperm and semen initial fructose. While initial hydrogen ion concentration (pH) and dead and abnormal sperm were increased (P<0.05). Live body weight (LBW), feed intake (FI) and relative weights of testes (RTW) and epididymis (REW) were significantly (P<0.05) decreased. Concentrations of thiobarbituric acid-reactive substances (TBARS) were significantly (P<0.05) increased in seminal plasma of rabbits treated with AlCl3 compared with control. While, activities of glutathione S-transferase (GST), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and acid phosphatase (AcP) were significantly (P<0.05) decreased. Ascorbic acid alone significantly increased LBW, FI, RTW, REW, semen characteristics and seminal plasma enzymes, and decreased the levels of free radicals. Also, the present study showed that ascorbic acid might be effective in the protection of aluminium-induced reproductive toxicity. It was suggested that AlCl3 exerted a significant adverse effect on reproductive performance of male rabbits. Furthermore, AA could be able to antagonize the toxic effects of AlCl3 and improved semen quality of male rabbit.     

Ameliorating effect of folic acid on chromium(VI)-induced changes in reproductive performance and seminal plasma biochemistry in male rabbits

Chromium hexavalent (Cr(VI)) is a biologically active oxidized state of chromium. It is involved in the redox cycle, with the production of reactive oxygen species. Free radical scavenging properties and possible antioxidant activity of folic acid (FA) have been reported; therefore, the present study examined possible protective effects of FA on the reproductive toxicity of potassium dichromate (K2Cr2O7) in male New Zealand white rabbits. We monitored reproductive performance, lipid peroxidation, enzyme activities and biochemical parameters in seminal plasma. Six rabbits per treatment group (and a control group) were exposed: 8.3 microg/kg FA; 5 mg/kg potassium dichromate (contains 3.6 mg chromium(VI)) and 5 mg/kg potassium dichromate+8.3 microg/kg FA. Results showed that semen quality deteriorated following potassium dichromate exposure. Testosterone levels, body weight (BW), relative weights of testes (RTW) and epididymis (REW) all decreased. Levels of thiobarbituric acid-reactive substances increased, whereas the activities of glutathione S-transferase, transaminases and phosphatases decreased in the seminal plasma. FA alone significantly increased BW, RTW, REW, semen characteristics and seminal plasma enzymes, and decreased the levels of free radicals. Furthermore, FA can be effective in the protection of chromium-induced reproductive toxicity.     

Effect of methionine supplementation on endothelial function, plasma homocysteine, and lipid peroxidation.

BACKGROUND: Acetaminophen (paracetamol) poisoning is a major source of morbidity and mortality. It has been proposed that methionine be incorporated into acetaminophen tablets routinely as a protective mechanism. Methionine has been shown to be effective in the treatment of acetaminophen toxicity and a combination preparation of acetaminophen and methionine may prevent toxicity. However, there has been some concern that chronic methionine supplementation may be associated with vascular disease. The aim of the study was to investigate if methionine supplementation causes changes in endothelial function, plasma homocysteine, or lipid peroxidation which may be associated with atherosclerosis. METHODS: Sixteen healthy volunteers were studied. Forearm blood flow in response to local intra-arterial infusion of acetylcholine to assess endothelium-dependent vasodilatation and sodium nitroprusside to assess endothelium-independent vasodilatation was measured by venous occlusion plethysmography. Plasma homocysteine and lipid peroxidation, measured as thiobarbituric acid reactive substances, were measured using high-performance liquid chromatography. Forearm vascular responses, plasma homocysteine concentrations, and thiobarbituric acid reactive substances were measured at baseline and following methionine supplementation. RESULTS: There was no significant difference in endothelial-dependent vascular responses after acute (methionine 250 mg orally, p > 0.05), 1 month of low-dose (methionine 250 mg daily, p > 0.05), or 1 week of high-dose (methionine 100 mg/kg daily, p > 0.05) methionine administration. There was no significant difference in plasma homocysteine concentrations after acute (p > 0.05) or 1 month of low-dose (p > 0.05) methionine administration. However, 1 week of high-dose methionine (100 mg/kg) administration daily significantly increased homocysteine concentrations (p < 0.0015). Thiobarbituric acid reactive substances were unchanged during the period of study (p > 0.05). CONCLUSIONS: Methionine supplementation does not impair endothelial-dependent vascular responses in healthy volunteers. Although high-dose methionine administration causes elevation of plasma homocysteine concentrations, doses similar to those used in combination preparations with acetaminophen do not affect plasma homocysteine concentrations.     

Effect of phensuccinal on lipid metabolism, lipid peroxidation, and antioxidant system activity in rabbits with dithiazone-induced diabetes

A three-month administration of phensuccinal improved glucose homeostasis, decreased the levels of total cholesterol, triglycerides, fatty acids, and low-density lipoproteins in the blood serum, and reduced the lipid peroxidation rate as compared to the untreated diabetic control. In addition, phensuccinal increased the content of the antiatherogenic high-density lipoprotein fraction and the related paraoxonase enzyme activity. The preventive effect of phensuccinal with respect to diabetic dyslipidemia development, together with the antioxidant action, show this compound to be a promising therapeutic means of preventing and/or reducing macrovascular complications in diabetic patients.     

魔芋葡甘聚糖对动脉粥样硬化家兔血清一氧化氮、血浆内皮素和脂质过氧化物的影响

目的 :观察魔芋葡甘聚糖预防用药对动脉粥样硬化 (AS)家兔血清一氧化氮 (NO) ,血浆内皮素(ET)、脂质过氧化物 (MDA)和超氧化物歧化酶(SOD)的影响。方法 :采用高胆固醇饲料喂饲另加牛血清白蛋白一次注射方法 ,建立家兔AS模型 ,随机分为对照组 (n =8) ,模型组 (n =8)和魔芋葡甘聚糖用药组 (n =8) ,各组在实验第 8周取血清标本测定血清NO ,血浆ET、MDA和SOD。结果 :与模型组比较 ,魔芋葡甘聚糖预防用药 8周 ,能提高NO和SOD活性 (P <0 .0 1) ,降低ET和MDA含量 (P <0 .0 1)。结论 :魔芋葡甘聚糖具有抗氧化、保护内皮功能和维持NO/ET平衡的作用     

Protective effect of ascorbic acid on netilmicin-induced lipid profile and peroxidation parameters in rabbit blood plasma

A drug may cause alteration in blood-lipid profile and induce lipid peroxidation phenomena on administration in the body. Antioxidant may play beneficial role to control the negative alteration in lipid profile and lipid peroxidation. In view of this context, the present in vivo study was carried out to evaluate the role of ascorbic acid as antioxidant on netilmicin-induced alteration of blood lipid profile and peroxidation parameters. Rabbits were used as experimental animals and blood was collected to estimate blood-lipid profiles, such as total cholesterol (TCh), high density lipoprotein cholesterol (HDL-Ch), low density lipoprotein cholesterol (LDL-Ch), very low density lipoprotein cholesterol (VLDL-Ch), triglycerides (Tg), phospholipids (PL), and total lipids (TL), as well as peroxidation parameters, such as malondialdehyde (MDA), 4-hydroxy-2-nonenal (HNE), reduced glutathione (GSH) and nitric oxide (NO). The results revealed that netilmicin caused significant enhancement of MDA, HNE, TCh, LDL-Ch, VLDL-Ch, Tg levels and reduction in GSH, NO, HDL-Ch, PL, TL levels. On co-administration, ascorbic acid was found to be effective in reducing netilmicin-induced negative alterations of the above parameters.     

Study of lipid peroxidation inhibition in human blood by several endogenous and exogenous compounds

Numerous studies suggest that lipid peroxidation is involved in the atherosclerosis and hemolytic disease processes. Nicanartine improves in vitro resistance of LDL (low density lipoproteins) to oxidation in the conjugated dienes model. Polarographic assays show that hemin-bound drugs inhibit erythrocyte membrane peroxidation. A method to measure the antioxidant capacity of plasma is proposed and tested in sickle cell disease. These in vitro results suggest drugs and drugs combination which could be efficient to inhibit lipid peroxidation in vivo.     

Inhibition of microsomal lipid peroxidation by alpha-tocopherol and alpha-tocopherol acetate.

1. The antioxidant effects of alpha-tocopherol and alpha-tocopherol acetate were assayed for the (a) oxygen uptake, (b) chemiluminescence and (c) malondialdehyde formation, of tert-butyl hydroperoxide-supplemented rat liver microsomes. 2. Oxygen uptake was inhibited 60% by both alpha-tocopherol and alpha-tocopherol acetate with the half-maximal effect at 5 nmol tocopherol/mg protein. Chemiluminescence and malondialdehyde formation were equally inhibited 35% by both tocopherols with half-maximal effects at 2 nmol tocopherol/mg protein. 3. The rate of O2 uptake by tocopherol-supplemented microsomes was dependent on O2 concentration. A 60% inhibition by 5 nmol tocopherol/mg protein at 0.2 mM O2 is decreased to 5% inhibition at 0.6 mM O2. 4. The inhibition of O2 uptake, chemiluminescence and malondialdehyde formation indicate that both alpha-tocopherol and alpha-tocopherol acetate have similar effects as free radical traps in the hydrophobic domain of biomembranes. The different inhibition observed at different O2 concentrations indicate competition between vitamin E and O2 by unoxygenated lipid radicals.     

Effects of moxonidine on corticocerebral blood flow under normal and ischemic conditions in conscious rabbits

Hypertension associated with excessive liberation of circulating and tissue catecholamines is an independent risk factor for further cardiovascular complications and an important predictor of stroke. Moxonidine is a centrally acting anti-hypertensive drug with potent action on I1-imidazoline receptors. It inhibits catecholamine release and is therefore expected to exert an antiadrenergic effect at various levels in the regulation of the cardiovascular system. The aim of this study was to investigate the effect of moxonidine (0.025-0.1 mg/kg, i.v.) on the normal and unilateral carotid occlusion-induced impaired corticocerebral blood flow (cCBF) determined by hydrogen polarography, on mean arterial blood pressure (MABP) and heart rate (HR) in conscious rabbits. Moxonidine produced a reduction of MABP and HR. On the other hand, after administration of the drug, a significant increase in the normal and impaired cCBF was observed. Because the improvement in cCBF was conspicuous in both normal and ischemic conditions, moxonidine might be beneficial not only in the treatment of hypertension but also in the management of cerebral ischemia.     

Nickel-induced plasma lipid peroxidation and effect of antioxidants in human blood: involvement hydroxyl radical formation and depletion of alpha-tocopherol

To provide evidence for the oxidative effect of nickel (Ni) treatment on blood, lipid peroxidation (LPO) and hydroxyl radical (*OH) generation were examined in human plasma. Nickel chloride induced LPO in plasma of human blood in vitro in a concentration-dependent (0-10 mM) and time-dependent (0-2 h) manner. The *OH production in plasma was quantified by measurement of conversion of salicylic acid (SA) into its hydroxylated products, 2,3- and 2,5-dihydroxybenzoate (DHB). The concentrations of 2,3- and 2,5-DHB in plasma increased in a concentration-dependent manner after Ni treatment for 1 h. Furthermore, a decreasing trend in alpha-tocopherol levels in plasma was observed after Ni treatment. Concurrent incubation with gluthathione (GSH), catechin (CTCH), and mannitol decreased lipid peroxidation and reduced *OH formation induced by Ni, but exacerbation of the decrease of alpha-tocopherol in plasma occurred with catechin.     

Inhibition of lipid peroxidation and cholesterol levels in mice by curcumin.

Effect of oral administration of curcumin (diferuloyl methane) on lipid peroxidation in various organs of mice like liver, lung, kidney and brain was studied in control animals as well as those given carbon tetrachloride, paraquat and cyclophosphamide. Oral administration of curcumin significantly lowered the increased peroxidation of lipids in these tissues produced by these chemicals. Administration of curcumin was also found to lower significantly the serum and tissue cholesterol levels in these animals, indicating that the use of curcumin helps in conditions associated with peroxide induced injury such as liver damage and arterial diseases.     

Human placental lipid peroxidation--II. NADPH and iron dependent stimulation of microsomal lipid peroxidation by paraquat

Paraquat, a widely used herbicide, was found to cause a marked stimulation of lipid peroxidation in the human placental microsomes in vitro. Both NADPH and chelated iron were necessary to observe paraquat-stimulated lipid peroxidation. The malondialdehyde accumulation in the incubation medium increased with increase in time, protein and paraquat concentration. The reaction did not exhibit the initial lag phase suggesting that endogenous membrane-bound antioxidants in human placental microsomes are either absent or present in extremely small quantities.     

Propranolol concentrations in blood serum, seminal plasma and saliva in man after a single oral dose.

A single dose of 80 mg racemic propranolol hydrochloride was administered by mouth to six healthy male volunteers. The mean concentration achieved in seminal plasma at 2 h after dosing was almost identical to that in blood serum. The concentrations of propranolol in seminal plasma and saliva were much less than those known to reduce sperm motility by 50% in vitro. The concentrations in saliva did not reflect those in blood serum. Propranolol in the dose administered in this study is unlikely to affect fertility by its presence in saliva or semen.     

Thiokynurenates prevent excitotoxic neuronal death in vitro and in vivo by acting as glycine antagonists and as inhibitors of lipid peroxidation.

Several derivatives of kynurenic and thiokynurenic acids were synthesized and tested for their ability to protect primary cultures of cerebellar granule cells against excitotoxic damage, and to affect the binding of [3H]glycine ([3H]Gly), [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA), [3H]3-(2-carboxypiperazine-4-yl-)propyl-1-phosphonic acid ([3H]CPP), [3H]kainic acid and [3H]N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP) to rat cortical membranes. Kynurenic and thiokynurenic acid derivatives with one or two halogens in position 5 or 7 were selective glycine antagonists, failing to affect N-methyl-D-aspartate (NMDA), kainate or AMPA sites at micromolar concentrations. 7-Cl-kynurenic, 7-Cl-thiokynurenic, 5,7-diCl-kynurenic and 5,7-diCl-thiokynurenic acids had similar IC50s for displacing [3H]Gly from its strychnine-insensitive site and for reducing the stimulated (0.5 microM NMDA and 1 microM glycine) [3H]TCP binding to cortical membranes. However, 7-Cl-thiokynurenic acid was particularly potent to prevent excitotoxic neuronal death in cultured cerebellar granule cells. This action may be ascribed to inhibition of lipid peroxidation, a property which was demonstrated for the 5- or 7-Cl derivatives of thiokynurenic acid. Furthermore, 7-Cl-thiokynurenic acid reduced excitotoxic damage caused by the injection of quinolinic acid in the rat striatum. Thus, 7-Cl-thiokynurenic acid appears to be a new compound with interesting antiexcitotoxic properties both in vitro and in vivo.     

Inhibition of plasma lipid peroxidation by anti-atherogenic antioxidant BO-653, 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran

BO-653, 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran, is a synthetic antioxidant which is now being developed as an anti-atherogenic drug. The antioxidant action of BO-653 against lipid peroxidation in rat plasma was studied and compared with its analogue BO-653M, 2,3-dihydro-5-hydroxy-4,6-di-methyl-2,2-dipentylbenzofuran, and vitamin E. BO-653 was readily incorporated into plasma by oral administration and it inhibited plasma lipid peroxidation more efficiently than vitamin E independent of the presence or absence of vitamin C. On the other hand, its analogue BO-653M having two methyl substituents in place of tert-butyl groups of BO-653 did not inhibit the lipid peroxidation in plasma as efficiently as BO-653, demonstrating clearly that the tert-butyl groups at the ortho-position play a key role in determining the antioxidant efficacy.     

Palm oil induced changes in ocular tissue lipid peroxidation, antioxidant enzymes and ATPases of rabbits in cadmium toxicity

This study determined the effect of supplementing rabbit diet with palm oil (PO) on lipid peroxidation, antioxidant enzymes and ATPases of different sections of the eyes in ocular cadmium toxicity. Twenty male New Zealand rabbits were randomly assigned to 4 groups of 5 rabbits in a study that lasted for 4 weeks. The control was given deionised water as eye drops and the other groups of rabbits were given eye drops of solution of 2mgkg(-1) body wt cadmium (as 3CdSO(4).8H(2)O). One test group was fed with the normal chow alone and the other test groups were fed with the chow fortified with either 5% or 10% palm oil. Ocular treatment of rabbit with cadmium significantly (P<0.05) reduced their weight compared with the control. Feeding the animals with palm oil (PO) improved the weights of the animals and decreased cadmium accumulation in the eye tissues. Lipid peroxidation level was raised by cadmium in the cornea, lens and retina with palm oil supplementation of the animal diet significantly (P<0.05) reducing the level of lipid peroxidation of the retina. Cadmium significantly (P<0.05) reduced antioxidant enzymes and ATPases in the eye tissues compared with the control. Feeding the rabbits with PO significantly (P<0.05) increased the activities of these enzymes in the retina to levels comparable with the control, with the 10% supplementation producing a more pronounced effect. The study shows that PO can alter cadmium accumulation, antioxidant enzymes and ATPases in ways which suggest that it offers protection of the eyes from ocular exposure to cadmium.     

Evaluation of alpha-tocopherol, probucol and ascorbic acid as suppressors of digoxin induced lipid peroxidation

Protective effects of three free radical scavengers, tocopherol (TOC), probucol (PR) and ascorbic acid (AA), on cardiotonic glycoside digoxin (DIG) induced lipid peroxidation in goat liver homogenate, have been studied by measuring malondialdehyde and glutathione contents as indicator parameters. The level of reduced glutathione decreased vis-a-vis malondialdehyde content increased in the drug treated samples in comparison with the controls. This suggests that DIG may have significant lipid peroxidation induction capacity. Considering lipid peroxidation as a toxicity mediating process, this may be related to the toxic potential of the drug. When the liver homogenate samples were incubated with antioxidant (TOC/PR/AA) in conjunction with the drug (DIG), lipid peroxidation was suppressed as indicated by increased level of reduced glutathione and decreased level of malondialdehyde in comparison with those of drug treated samples. This indicates that TOC, PR and AA may have considerable suppressive action on DIG induced lipid peroxidation. Thus, these antioxidants merit further extensive study to explore their potential in reducing DIG induced toxicity that may be mediated by free radical mediated process.     

The influence of pindolol and hydrochlorothiazide on blood pressure, and plasma renin and plasma lipid levels

After three weeks' administration of placebo, three groups of eight patients with moderate hypertension were randomly assigned to single daily dose, double-blind treatment with either pindolol 15 mg, hydrochlorothiazide 50 mg, or a combination of both for eight weeks. All determinations were made 24 hours after ingestion of a dose. Reductions in supine, sitting, and standing systolic and diastolic blood pressure were greater in patients receiving hydrochlorothiazide than in those administered pindolol; however, the greatest reductions were registered in individuals receiving combination therapy. Mean basal plasma renin activity rose significantly from 0.45 +/- 0.44 to 1.42 +/- 1.31 ng/mL/hr and from 0.67 +/- 0.46 to 1.27 +/- 0.83 ng/mL/hr in patients receiving hydrochlorothiazide and combination therapy, respectively, but there was no change in those administered pindolol. Hydrochlorothiazide and combination therapy increased mean total cholesterol levels from 247 +/- 25 to 263 +/- 37 mg/dL and 198 +/- 36 to 211 +/- 33 mg/dL, respectively, at eight weeks, and both increased mean triglyceride concentrations at two weeks. Pindolol did not show any tendency to alter lipid levels. Pindolol should be given twice daily. At 15 mg daily, it has little or no effect on basal plasma renin activity or plasma lipid levels.