Effect of gold nanoparticles on glutathione and malondialdehyde levels in liver,lung and heart of rats

We studied the effect of gold nanoparticles (NPs) on oxidative stress markers including reduced glutathione (GSH) and malondialdehyde (MDA) in different organs of rats. Adult male Wistar-Kyoto rats were randomly divided into 3 groups of 5 animals each. One group served as control and received vehicle only. The remaining two groups were treated with 50 μl of 10 nm sized gold NPs, daily for 3 and 7 days, respectively. The rats were sacrificed 24 h after the last injection of NPs. Administration of gold NPs did not cause any significant change in GSH levels in liver, lung and heart on day 3 or day 7. There was no significant effect of gold NPs on MDA levels in lung and heart whereas significant increases in MDA levels were found in the liver of rats treated with gold nanoparticles on both 3 and 7 days post-dosing (ANOVA F = 7.113, P = 0.010). In conclusion, the findings of this preliminary study suggest that gold NPs of 10 nm diameter produce significant lipid peroxidation in rat liver however lungs and heart do not show any oxidative stress. Further studies are warranted to examine the effects of a broader dose range of gold NPs on the levels of free radical indices in different organs of rats.     

Inconsistent suppression of nocturnal pineal melatonin synthesis and serum melatonin levels in rats exposed to pulsed DC magnetic fields

The purpose of these experiments was to determine whether the exposure of rats at night to pulsed DC magnetic fields (MF) would influence the nocturnal production and secretion of melatonin, as indicated by pineal N-acetyltransferase (NAT) activity (the rate limiting enzyme in melatonin production) and pineal and serum melatonin levels. By using a computer-driven exposure system, 15 experiments were conducted. MF exposure onset was always during the night, with the duration of exposure varying from 15 to 120 min. A variety of field strengths, ranging from 50 to 500 μT (0.5 to 5.0 G) were used with the bulk of the studies being conducted using a 100 μT (1.0 G) field. During the interval of DC MF exposure, the field was turned on and off at 1-s intervals with a rise/fall time constant of 5 ms. Because the studies were performed during the night, all procedures were carried out under weak red light (intensity of <5 μW/cm²). At the conclusion of each study, a blood sample and the pineal gland were collected for analysis of serum melatonin titers and pineal NAT and melatonin levels. The outcome of individual studies varied. Of the 23 cases in which pineal NAT activity, pineal melatonin, and serum melatonin levels were measured, the following results were obtained; in 5 cases (21.7%) pineal NAT activity was depressed, in 2 cases (8.7%) studies pineal melatonin levels were lowered, and in 10 cases (43.5%) serum melatonin concentrations were reduced. Never was there a measured rise in any of the end points that were considered in this study. The magnitudes of the reductions were not correlated with field strength (i.e., no dose-response relationships were apparent), and likewise the reductions could not be correlated with the season of the year (experiments conducted at 12-month intervals under identical exposure conditions yielded different results). Duration of exposure also seemed not to be a factor in the degree of melatonin suppression. The inconsistency of the results does not permit the conclusion that pineal melatonin production or release are routinely influenced by pulsed DC MF exposure. In the current series of studies, a suppression of serum melatonin sometimes occurred in the absence of any apparent change in the synthesis of this indoleamine within the pineal gland (no alteration in either pineal NAT activity or pineal melatonin levels). Because melatonin is a direct free radical scavenger, the drop in serum melatonin could theoretically be explained by an increased uptake of melatonin by tissues that were experiencing augmented levels of free radicals as a consequence of MF exposure. This hypothetical possibly requires additional experimental documentation. Bioelectromagnetics 19:318–329, 1998. © 1998 Wiley-Liss, Inc.     

Potential protective effects of melatonin on bone marrow of rats exposed to cytotoxic drugs

Myelosuppression is the most serious, dose limiting, toxicity of cytotoxic drugs. Efforts to protect the bone marrow have been only variably successful, and no agreement exists on how to approach this problem. Melatonin, the major hormonal product of the pineal gland, is supposed to have both chemoprotective and myelostimulatory effects. This experimental study was carried out to test these two effects on the bone marrow of rats, daily intraperitoneally injected with 100 microg melatonin. Injection of 10 mg aracytin for 10 days produced a significant (P < 0.01) decrease in red blood cells count (RBCs), total leucocytic count, as well as platelets count. When melatonin was injected along with aracytin, it would significantly increase (P < 0.05) RBC count and (P < 0.01) blood platelet count. Injection of melatonin after aracytin treatment would significantly increase (P < 0.01) RBC, total leucocytic and platelet counts in comparison with rats treated with aracytin only. The effects of melatonin were more clear in rats treated with it after aracytin injection than those treated with melatonin and aracytin at the same time. Furthermore, it was found that aracytin produced a significant (P < 0.01) decrease in serum total proteins, albumin, and significantly increased the (P < 0.01) albumin/globulin ratio. Melatonin injection would significantly increase (P < 0.01) total protein, globulin, and significantly decrease (P < 0.01) the albumin/glubulin ratio when injected either with aracytin or after aracytin treatment. These results indicate that melatonin protects bone marrow, lymphoid tissues from damaging effect of cytotoxic drugs, as well as stimulating the suppressed bone marrow.     

Effect of carnitine on malondialdehyde, taurine and glutathione levels in heart of rats subjected to myocardial stress by isoproterenol

The effect of carnitine on free fatty acid, malondialdehyde, taurine and glutathione levels in myocardium was studied in rats administered isoproterenol to induce a stress in the myocardium resulting in myocardial ischaemia. Carnitine decreased the levels of free fatty acid and malondialdehyde (an index of lipid peroxidation) when compared to control rats given isoproterenol alone. Taurine and glutathione also registered a fall in the carnitine treated animals when compared to rats treated with isoproterenol alone. The results indicate that carnitine by decreasing the levels of these parameters helps the myocardium to survive from the stress induced by isoproterenol.     

Pulmonary and hepatic glutathione levels, glutathione shuttle enzymes and lipid peroxidation in rats exposed intratracheally to coal fly ash

Fly ash and fly ash residue increased the formation of conjugated dienes and the levels of oxidized glutathione (GSSG) and reduced the levels of reduced glutathione (GSH) in lung and liver whereas fly ash extract administration had no effect on the formation of conjugated dienes and glutathione levels in lung and liver. Fly ash and fly ash residue reduced the activity of glutathione reductase both in lung and liver but did not alter the activity of glutathione peroxidase. Fly ash and fly ash extract significantly increased glucose-6-phosphate dehydrogenase activity in lung whereas in liver, fly ash and fly ash residue reduced the activity of glucose-6-phosphate dehydrogenase. Fly ash residue did not alter the activity of glucose-6-phosphate dehydrogenase in lung whereas fly ash extract was not effective in liver.     

Effects of zinc deficiency and supplementation on malondialdehyde and glutathione levels in blood and tissues of rats performing swimming exercise

The aim of the study was to investigate the effects of zinc deficiency and supplementation on lipid peroxidation and glutathione levels in blood and in some tissues of rats performing swimming exercise. Forty adult male Sprague-Dawley rats were divided into four groups: group 1, zinc-deficient consisted of swimming rats; group 2 consisted of zinc-supplemented swimming rats; groups 3 and 4 were the swimming and nonswimming controls, respectively. The levels of malondialdehyde and glutathione were measured after 4 wk of zinc-deficient or zinc-supplemented diet and 30 min of swimming exercise daily. The erythrocyte glutathione levels of groups 2 and 4 were significantly higher than those of groups 1 and 3 (p<0.01). The plasma malondialdehyde level of group 1 was significantly higher than all other groups. The glutathione levels in liver, kidney, striated muscle, and testes of group 2 were higher than in the other groups (p<0.01) and higher in kidney and striated muscle of group 3 than in groups 1 and 4 (p<0.01). The tissue malondialdehyde levels of striated muscle, liver, kidney, and testes of group 1 were significantly higher than for all other groups (p<0.01). Our findings suggest that both swimming exercise and zinc deficiency result in an increase of lipid peroxidation in tissues and that zinc supplementation prevents these alterations by the activation of the antioxidant system.     

Acetylcholine in the brain of rats exposed to acute irradiation

A two-fold increase in acetylcholine, that can randomly be released by brain synaptosomes, is registered 60 min following whole-body X-irradiation of rats with a dose of 0.21 C/kg; depolarization of the synaptosome membranes by potassium chloride increases the release of acetylcholine the augmentation of the release in this case being lower than that in the control. The initial rate of spontaneous neuromediator release from synaptosomes grows by 80 per cent whereas after depolarization of synaptosome membranes by potassium chloride, by 15 per cent. There is a 2.5-fold increase in the maximum rate of a highly specific uptake of choline with Km value being constant. Acetylcholine content of gray substance of irradiated rat brain is invariable.     

Antioxidant enzyme activities and malondialdehyde, glutathione and methemoglobin concentrations in channel catfish exposed to DEF and n-butyl mercaptan

Indicators of free-radical or oxidant-mediated responses were quantified in channel catfish, Ictalurus punctatus, exposed to the organophosphorus herbicide DEF and its metabolite, n-butyl mercaptan (nBM). The activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase did not vary significantly with toxicant or dose. The concentrations of reduced glutathione (GSH) and malondialdehyde (MDA) did not vary significantly with toxicant or dose. The percentage of methemoglobin increased in the nBM-exposed fish with dose, up to 16.5% of total hemoglobin. The DEF-exposed catfish had no significant increases in methemoglobin compared to controls.     

The effects of melatonin on glutathione peroxidase activity in serum and erythrocytes after adriamycin in normal and pinealectomised rats

INTRODUCTION: Adriamycin (ADR) is a potent chemotherapeutic agent, effective in the treatment of leukaemias, lymphomas and many solid tumours. However, its clinical usage is often limited by cardiotoxicity, induced by oxygen radical damage of the membrane lipids. Melatonin (MEL) is a well-known antioxidant. It has been shown that MEL can scavenge free radicals, both directly and indirectly, stimulating the activity of antioxidative enzymes such as glutathione peroxidase (GSH-Px). THE AIM OF THE STUDY: The aim of the study was to examine the effect of MEL on serum and erythrocyte GSH-Px activity after ADR in normal and pinealectomised rats. MATERIAL AND METHODS: Wistar rats were divided into the three groups: control animals (Intact), sham-operated (Sham-PX) and pinealectomised (Px). Each of the groups was divided into four subgroups, injected with: 1--saline, 2--MEL, 3--ADR and 4--ADR + MEL. ADR was administered 2 months after Px as a single dose (15 mg/kg, i.p.) 1 hour after the fourth melatonin injection. Melatonin (5 mg/kg, i.p.) was administered for 4 days before and 2 days after ADR. After 6 days of treatment, the rats were killed by decapitation. Their blood was collected for measurements. RESULTS: In serum GSH-Px activity decreased in all the groups after ADR. Pinealectomy decreased the activity of the enzyme in all the groups of animals examined. In erythrocytes GSH-Px decreased after ADR in the Px-animals. The effect of pinealectomy on erythrocyte GSH-Px activity was not as strongly expressed as serum GSH-Px activity. MEL did not change GSH-Px activity after ADR. CONCLUSION: Melatonin, in pharmacological concentrations, did not influence the activity of GSH-Px, either in normal or in pinealectomised rats after ADR. A deficiency of endogenous melatonin production may inhibit GSH-Px activity.     

The effect of melatonin on eye lens of rats exposed to ultraviolet radiation

We investigated the influence of exogenously administered melatonin on adult rats eye lenses exposed to ultraviolet radiation (UV) A and B ranging from 356-254 nm irradiation at 8 microW/cm(2). Rats exposed to this range of UV for 15 min for one week showed a significant (P<0.05) reduction in antioxidant enzymes activities; superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and elevated (P<0.001) lipid peroxidation served as an index of cellular damage by free radicals. UV-radiation significantly (P<0.001) elevated calcium ions (Ca(2+)) and lactate dehydrogenase (LDH) activity in lenses. Depleting animals of their stores of important intracellular antioxidant and elevating lenticular Ca(2+) by UV irradiation, may be the main cause of lens opacification. Melatonin injection with radiation significantly reduced (P<0.05) lipid peroxidation, Ca(2+) and (P<0.001) for LDH. When melatonin was injected after radiation, SOD and GSH-Px enzyme activities increased significantly (P<0.01), and lipid peroxidation, Ca(2+) levels and LDH activities were reduced significantly. Melatonin injection after UV radiation was as effective as melatonin treatment concurrent with UV irradiation. We conclude that melatonin may protect the eye lens from the damaging effects of UV exposure, and its actions protect lens from oxidative stress, elevating Ca(2+) levels, which are considered as an important causes of cataractogenesis.     

Effects of dexfenfluramine on serotonin levels of mice ileum, contractility, glutathione and malondialdehyde level

Dexfenfluramine is one of the anorectic drugs that suppresses food intake which acts via inhibition of reuptake of serotonin into brain terminal. Gastrointestinal tract is the main source of peripheral serotonin which is involved in the regulation of gastrointestinal motility. During the use of anorectic drugs, the antioxidant defence is affected especially by reactive oxygen species. The purpose of this study to search: The effect of dexfenfluramine on serotonin levels of ileum and the effect of dexfenfluramine on ileal contractility and oxidative stress. Materials and Methods: Twenty-two adult male Swiss-albino mice were divided two groups (1) Control, (2) Dexfenfluramine treated (i.p. twice a day 0.2 mg kg⁻¹ in 0.2 ml saline solution for 7 days). Animal body weights were recorded at the beginning and at the end of the experimental period. Ileum tissues contractile responses to different concentrations of KCl and acethycholine were recorded on polygraph. In the meantime ileal tissue malondialdehyde, a product of lipid peroxidation, and glutathione, endogenous antioxidant levels were assessed by spectrophotometric methods. Ileal tissue serotonin level determined by immunohistochemical method. Body weights decrease and ileal contractile response of acethycholine increased significantly by dexfenfluramine treatment. Meanwhile, ileum glutathione levels decreased and malondialdehyde levels increased in dexfenfluramine treated group. Immunohistochemical detection showed that ileal serotonin levels increased by dexfenfluramine treatments. As a conclusion, there is a relationship between increased ileal contractility and oxidant status in dexfenfluramine treated animals. These effects can be related by increased serotonin levels which is induced by dexfenfluramine in ileum. (Mol Cell Biochem xxx: 151–157, 2005)     

Pinealectomy and melatonin administration in rats: their effects on plasma leptin levels and relationship with zinc

The aim of this study was to examine effects of pinealectomy and melatonin administration plasma leptin levels and its relationship with zinc in rats. The study was conducted on 40 adult male Sprague-Dawley rats. They were divided into four groups each containing 10 animals. Group 1 served as control. Group 2 was pinealectomized group. Animals in Group 3 were pinealectomized and injected with melatonin (3 mg/kg/day, ip). Group 4 received melatonin alone (3 mg/kg/day, ip). At the end of the experiments, all animals were decapitated and trunk blood collected. Plasma leptin and zinc levels were determined by radioimmunoassay and Atomic Absorption Spectrophotometer methods, respectively. Although mean weights of the animals at the beginning were not significantly different among the groups, the mean weight of the pinealectomized group was found to be significantly lower than all other groups at the end of a six-month period (p < 0.01). Plasma leptin and zinc levels were the highest in melatonin-administered group (group 4; p < 0.01). The lowest plasma leptin and zinc levels were obtained in the pinealectomized group (group 2; p < 0.01). Changes in these two parameters were not statistically significant in groups 1 and 3. Our findings indicate that pinealectomy results in a decrease in leptin and zinc levels in rats, and that melatonin administration to pinealectomized rats prevents the decrease in the these parameters. In addition, long-term administration of melatonin to rats leads to an increase in both leptin and zinc concentrations.     

Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth

Rats exposed to 60-Hz electric fields of either 10, 65, or 130 kV/m from conception to 23 days of age exhibited reduced peak nighttime pineal melatonin contents compared to unexposed controls. As a group, the exposed rats also exhibited a phase delay, estimated at approximately 1.4 hours, in the occurrence of the nocturnal melatonin peak. No clear dose-response relationship was noticed over the range of electric field strengths used as treatments in these experiments. These are the first studies concerned with the effects of electric field exposure on the pineal melatonin rhythm in immature rats. The findings are generally consistent with those obtained using adult rats, where electric field exposure has been shown to abolish the nighttime rhythm in pineal melatonin concentrations.     

Structure-functional states of liver mitochondrial membranes of rats exposed to irradiation

The effect of the low dose gamma-irradiation (270 cGy--one-fold; 90 cGy per day during 3 days) on oxidative phosphorylation, lipid peroxidation, microviscosity of the annular and free lipids membrane, and membrane protein structural state was studied. The post-radiation influence on membrane functional activity and structural state in accordance with the irradiation regimes was established.     

Morphology of the oral mucosa in rats exposed to increased phosphorus levels

The experiments on rats kept for 1, 2, 3 and 4 months in phosphorous-producing workshops revealed the influence of elementary phosphorous and its nonorganic derivatives on the mouth mucosa tissues. At the early stages of the experiments the above agents caused the increase in the number of the epithelial layer cell elements, and strengthening of the keratosis process, leading to the development of hyperkeratosis. By the end of the experiment the development of dystrophic and atrophic processes in the epithelium were observed, which sometimes caused thinning of the epithelial layer. The connective tissue of submucous basis was characterized by microcirculation disorders and dystrophic disturbances of blood vessel walls becoming more pronounced by the end of the experiment.     

Disorders of vaginal development in the progeny of white rats exposed to x-ray irradiation

One hundred and twenty white rat embryos 13-22-day-old have been irradiated with x-rays (the dose 250 R) on the 12th-14th day of embryogenesis. The embryos have been divided into series of sagittal, frontal, transversal sections and stained by means of general histological methods. The irradiation performed on the days mentioned does not affect formation of the paramesonephric ducts. In all the experimental animals the caudal end of the paramesonephric duct is separated from the mesonephric duct as a solid cellular cord in which the lumen appears later. In the experimental females the disturbances developed after irradiation are manifested first of all in retardation of the main stages of the organ's formation; the retardation is observed: in fusion of the paramesonephric ducts, in resorption of the medial septum between the fused ducts, in separating the sinuous part of the vagina from the urogenital sinus, in recanalization of the vaginal epithelial cord. More severe lesions are presented as agenesia of the vaginal sinuous part and as its atresia represented by a transversal septum of the organ. The disorders in the vagina development are depended on massive primary necrobiotic radial lesions of the mesenchymal cells around the epithelial anlages of the small pelvis.     

Antioxidative enzyme and glutathione S-transferase activities in diabetic rats exposed to long-term ASA treatment

Low-dose acetylsalicylic acid (ASA) treatment is a standard therapeutic approach in diabetes mellitus for prevention of long-term vascular complications. The aim of the present work was to investigate the effect of long-term ASA administration in experimental diabetes on activities of some liver enzymes: glutathione peroxidase (GSHPx), catalase, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione S-transferase (GST). Blood glucose, glycated hemoglobin, as well as plasma ALT and AST activities increased in rats with streptozotocin-induced experimental diabetes. The long-term hyperglycemia resulted in decreased activities of GSHPx (by 26%), catalase (by 34%), GST (by 38%) and G6PDH (by 27%) in diabetic animals. We did not observe increased accumulation of membrane lipid peroxidation products or altered levels of reduced glutathione in livers. The linear correlation between blood glucose and glycated hemoglobin in diabetic animals was distorted upon ASA treatment, which was likely due to a chemical competition between nonenzymatic protein glycosylation and protein acetylation. The long-term ASA administration partially reversed the decrease in GSHPx activity, but did not influence the activities of catalase and GST in diabetic rats. Otherwise, some decrease in these parameters was noted in ASA-treated nondiabetic animals. Increased ASA-induced G6PDH activity was recorded in both diabetic and nondiabetic rats. While both glycation due to diabetic hyperglycemia and ASA-mediated acetylation had very similar effects on the activities of all studied enzymes but G6PDH, we conclude that non-enzymatic modification by either glucose or ASA may be a common mechanism of the observed convergence.     

Effect of melatonin administration on DNA damage and repair responses in lymphocytes of rats subchronically exposed to lead

In humans, autosomal dominant or X-linked disease can arise through a phenomenon termed haploinsufficiency, where one remaining wild-type allele is insufficient for function. In model organisms, the impact of heterozygosity can be tested directly with engineered mutant alleles or in a hemizygous state where the expression of one allele is abrogated completely. This review will focus on haploinsufficiency as it relates to telomerase and telomere length maintenance and, citing selected examples in various model organisms, it will discuss how the problem of gene dosage relates to telomere function in normal and diseased states.     

Thyroid hormone levels in rats exposed to alcohol during development

Maternal ingestion of alcohol appears to cause a pattern of congenital anomalies with a reduction of pre- and postnatal growth in the offspring. In order to study the possible implication of thyroid function in the effects of pre- and/or postnatal exposure to alcohol, we have studied serum thyroxine (T4) and triiodothyronine (T3) levels in rats from alcohol-fed mothers during the postnatal period (0-50 days). Blood alcohol levels of ethanol-treated pregnant rats were approximately equal to 20-25 mM and their serum T4 levels were decreased, compared with the pair-fed controls, at 15 and 21 days of gestation. No significant changes were observed in T3 levels. Prenatal alcohol exposure was associated with a decrease in both T4 and T3 levels in pups at birth. Although T4 levels continued reduced in the 40-50 days of the postnatal period, no clear effects were observed on T3 levels during this time. Moreover, the more marked alterations were obtained when the offspring were postnatally and pre + postnatally exposed to alcohol. Significant decreases were found in both T4 and T3 levels following postnatal exposure, except at the 20-25th day when a marked but transient increase in T4 levels was observed. These results indicate that alcohol exposure disturbs the hypothalamo-pituitary-thyroid axis, as measured by T3 and T4 hormone levels, mainly when the rats are exposed during the postnatal period.     

Effect of splenosid on lipid peroxidation process and glutathione antioxidant system in rats exposed to fractionated radiation

The dynamics of lipid peroxidation, antioxidant glutathione system condition in blood and viscerals (brain, heart, liver, spleen) of rats which were fractionally irradiated (10 fractions) in the total dose 1.0 Gy and oxidative homeostasis increase of primary and secondary lipid peroxidation products and glutathione system disturbances were established in the irradiated rats. The administration of splenosid diminished the disturbances of oxidative homeostasis but does not completely normalize the latter. The administration of splenosid during the irradiation course and after its finishing is more effective than only during the irradiation course.