Dose- and time-dependent effects of sulfur mustard on antioxidant system in liver and brain of rat

This study investigates the dose- and time-dependent effects of sulfur mustard (SM) on antioxidant system and lipid peroxidation in liver and brain of rats. For this purpose, male Wistar rats were randomly divided into eight groups and treated as follows: group 1 as control and groups 2-8 as experimental groups that received SM (1-80 mg/kg) through intraperitoneal injection. Rats were killed after 2, 7 and 14 days of exposure. SM dose-dependently decreased body weight. Superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) activities in liver were significantly increased at SM doses lower than 10 mg/kg after 2 and 7 days of exposure. However, the recovery of these parameters was observed after 14 days. At these concentrations, no significant change in glutathione (GSH) and malondialdehyde (MDA) levels were observed. At doses higher than 10 mg/kg, SM significantly decreased SOD, CAT, glutathione peroxidase (GPX), and GST activities in liver and brain and decreased glutathione reductase (GR) activity in liver, which was associated with a depletion of GSH and increased MDA level. Present data indicate that the effect of SM is dose- and time-dependent and at higher doses (>10 mg/kg) induces an oxidative stress response by depleting the antioxidant defense systems and increasing lipid peroxidation in liver and brain of rats.     

The effect of lovastatin on oxidative stress and antioxidant enzymes in hydrogen peroxide intoxicated rat

Oxidative stress has been linked to the development of many diseases and hastens the progression of cardiovascular diseases. Since lovastatin is used worldwide as a cholesterol lowering drug, the present study was undertaken to evaluate the antioxidant property of lovastatin against H₂O₂ induced oxidative stress in rats. Four study groups of rats of four animals each were treated with DMSO (control), H₂O₂ (OS), lovastatin (L) and H₂O₂ + lovastatin (OSL). On the 15th day the animals were sacrificed, and the liver and heart tissues were analyzed for oxidative stress biomarkers and anti-oxidant enzymes. Results of the OSL-group showed a reduction in thiobarbituric acid reactive substances in liver (42.7%) and heart tissue (8%) compared with the control group. An increase was observed in the activity of the antioxidant enzymes, catalase (34.6% in liver and 33.3% in heart) and glutathione peroxidase (50.5% in liver and 34.7% in heart). A commensurate increase in the activity of G6PDH was observed indicating an enhanced requirement of NADPH. The ratio GSH:GSSG in liver (1.05) and heart (0.84) was satisfactorily regulated compared to the control group (1.01 in liver and 0.93 in heart). These results suggest that lovastatin possesses antioxidant activity and reduces oxidative stress.     

Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain

During the perinatal period, the central nervous system (CNS) is extremely sensitive to metals, including methylmercury (MeHg). Although the mechanism(s) associated with MeHg-induced developmental neurotoxicity remains obscure, several studies point to the glutathione (GSH) antioxidant system as an important molecular target for this toxicant. To extend our recent findings of MeHg-induced GSH dyshomeostasis, the present study was designed to assess the developmental profile of the GSH antioxidant system in the mouse brain during the early postnatal period after in utero exposure to MeHg. Pregnant mice were exposed to different doses of MeHg (1, 3 and 10 mg/l, diluted in drinking water, ad libitum) during the gestational period. After delivery, pups were killed at different time points - postnatal days (PND) 1, 11 and 21 - and the whole brain was used for determining biochemical parameters related to the antioxidant GSH system, as well as mercury content and the levels of F(2)-isoprostane. In control animals, cerebral GSH levels significantly increased over time during the early postnatal period; gestational exposure to MeHg caused a dose-dependent inhibition of this developmental event. Cerebral glutathione peroxidase (GPx) and glutathione reductase (GR) activities significantly increased over time during the early postnatal period in control animals; gestational MeHg exposure induced a dose-dependent inhibitory effect on both developmental phenomena. These adverse effects of prenatal MeHg exposure were corroborated by marked increases in cerebral F(2)-isoprostanes levels at all time points. Significant negative correlations were found between F(2)-isoprostanes and GSH, as well as between F(2)-isoprostanes and GPx activity, suggesting that MeHg-induced disruption of the GSH system maturation is related to MeHg-induced increased lipid peroxidation in the pup brain. In utero MeHg exposure also caused a dose-dependent increase in the cerebral levels of mercury at birth. Even though the cerebral mercury concentration decreased to nearly basal levels at postnatal day 21, GSH levels, GPx and GR activities remained decreased in MeHg-exposed mice, indicating that prenatal exposure to MeHg affects the cerebral GSH antioxidant systems by inducing biochemical alterations that endure even when mercury tissue levels decrease and become indistinguishable from those noted in pups born to control dams. This study is the first to show that prenatal exposure to MeHg disrupts the postnatal development of the glutathione antioxidant system in the mouse brain, pointing to an additional molecular mechanism by which MeHg induces pro-oxidative damage in the developing CNS. Moreover, our experimental observation corroborates previous reports on the permanent functional deficits observed after prenatal MeHg exposure.     

The interplay of glutathione-related processes in antioxidant defense

This review summarizes current knowledge on glutathione (GSH) associated cellular processes that play a central role in defense against oxidative stress. GSH itself is a critical factor in maintaining the cellular redox balance and has been demonstrated to be involved in regulation of cell signalling and repair pathways. Enhanced expression of various enzymes involved in GSH metabolism, including glutathione peroxidases, γ-glutamyl cysteinyl synthetase (γ-GCS), glutathione S-transferases (GST) and membrane proteins belonging to the ATP-binding cassette family, such as the multidrug resistance associated protein, have all been demonstrated to play a prominent role in cellular resistance towards oxidative stress. This review stresses the fact that a co-ordinate interplay between these systems is essential for efficient protection against oxidative stress.     

Effects of trichlorfon on malondialdehyde and antioxidant system in human erythrocytes

Organophosphorus insecticides may induce oxidative stress leading to generation of free radicals and alteration in antioxidant system. The aim of this study was to examine the potency of trichlorfon, an organophosphate insecticide, to induce oxidative stress response in human erythrocytes in vitro. For this purpose trichlorfon solutions in different concentrations and erythrocyte solutions were incubated at 37 °C for 60 min. At the end of the incubation time, malondialdehyde (MDA), an end product of lipid peroxidation, total glutathione, reduced glutathione (GSH) levels, activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) enzymes were determined by spectrophotometric methods. Trichlorfon increased MDA formation depended on the concentration. On the other hand, decreases in the GSH-Px activity, GSH levels and increases in the total glutathione levels, SOD and CAT activities were seen in the studied concentrations. The present findings indicate that the in vitro toxicity of trichlorfon may be associated with oxidative stress.     

Effect of d-amphetamine,ethanol and genever on learning in the rat

The effect of oral administration of d-amphetamine (5 mg/kg), ethanol (2.5 g/kg), genever (equivalent to 2.5 g/kg ethanol) and the combinations d-amphetamine-ethanol and d-amphetamine-genever was studied on learning in the rat, using a shuttle-box in 4 sessions at 24 hr intervals. Acquisition was significantly favored by all treatments, being more constant in the 4 sessions when combinations d-amphetamine-ethanol and d-amphetamine-genever were administered.     

Glutathione dependent detoxication in adult rat hepatocytes under various culture conditions

In order to obtain more information concerning the effects of culture and medium conditions on the glutathione dependent detoxication system in hepatocyte cultures, glutathione reductase (GR) and glutathione peroxidase (GPx) activities were studied in both pure cultures of adult rat hepatocytes and their co-cultures with rat epithelial cells. Cells were isolated either with an oxygen saturated Krebs Henseleit buffer (KHB) or with a non-gassed Hepes buffer. As medium conditions, additions of 10% fetal calf serum (FCS), 25 mM nicotinamide, 0.1 M selenium and 2% dimethylsulphoxide, respectively, to the culture medium were examined. It was found that co-cultures of rat hepatocytes can cope better with oxidative stress than pure cultures do. This conclusion was reached from the following observations. When oxygenated KHB was used as isolating buffer, GR and GPx activities increased during the first days of pure culture and then slowly decreased. This was observed for all the medium conditions studied and no significant differences between the different media could be observed. For co-cultures, however, after some initial variations GR and GPx activities reached stabilized levels which were not only significantly lower than those observed for pure cultures, but were also maintained throughout the whole culture period. Supplementation of the medium had no effect on these findings with the exception of high GPx activities when Se was added to the co-culture medium. When Hepes buffer with a low oxygen content was used in cell isolation, pure cultures showed significantly lower GR and GPx activities than those first mentioned. Both approached the values measured for cocultures. The shape of the enzymatic activity curve as a function of culture time remained essentially unchanged. In co-cultures no significant differences could be observed in GPx activities when both perfusion techniques were involved, with the exception of the measurements done during the first 2 days of co-culture. Using the non-gassed Hepes buffer instead of the oxygenated KHB had no statistical effect on the GSH content of the hepatocytes in either of the two culture systems.     

In vivo changes in antioxidant system and protective role of selenium in chlorpyrifos-induced subchronic toxicity in bubalus bubalis

Chlorpyrifos, an organophosphate, is one of the widely used insecticides for control of pests in various agricultural and animal husbandry operations. The objective of the present investigation was to assess the effect of subchronic exposure of chlorpyrifos on the antioxidant status of buffalo calves and to perceive the role of selenium in cases of chlorpyrifos toxicity. Chlorpyrifos at a dose rate of 0.05 mg/kg per day for 20 consecutive weeks, significantly elevated the enzymic activity of glutathione peroxidase (GPx) (54.8%), glutathione reductase (GR) (79.4%), glutathione-S-transferase (GST) (34.2%), glucose-6-phosphate dehydrogenase (G6PD) (33.2%), superoxide dismutase (SOD) (19.3%) and catalase (CAT) (63.8%). The altered antioxidant status was well evident from the depleting glutathione levels and a two-fold rise in the extent of lipid peroxidation. Supplementation of selenium in the form of sodium selenite @ 0.05 mg/kg per day for 20 weeks in chlorpyrifos intoxicated calves had a marked beneficial effect on the overall antioxidant potential of the animals as evident by no significant alteration in the extent of lipid peroxidation, levels of blood glutathione and activities of various antioxidant enzymes viz. GST, GR, SOD, CAT and G6PD. There was only a significant increase in the activity of GPx to the tune of 27.4%. Therefore, on the basis of the present investigation it can be suggested that oxidative stress is one of the main mechanism involved in chlorpyrifos toxicity and supplementation with sodium selenite in such cases can have significant beneficial and therapeutic effects.     

Stress-induced facilitation of acoustic startle after d-amphetamine administration

Administration of d-amphetamine enhanced the startle response to an auditory stimulus. In contrast to saline treated mice, startle activity after amphetamine administration did not wane with repeated exposure to the auditory stimulus. Rather, the effects of amphetamine on startle activity increased as a function of stimulus presentation. Whereas exposure to isolation stress or inescapable shoch had no effect on startle activity, both types of stress potentiated the effects of amphetamine on startle arousal. The observation that stress sensitized animals to later amphetamine administration is consistent with the effects of stress on other amphetamine behaviors, e.g., stereotypy. Results were related to the development of dopamine post-synaptic receptor supersensitivity after exposure to stress and were discussed in terms of the role played by stress in the expression of behavioral arousal. in the etiology of schizophrenia.     

Isolation of chebulic acid from <Emphasis Type="Italic">Terminalia chebula</Emphasis> Retz. and its antioxidant effect in isolated rat hepatocytes

A hepatoprotective compound was isolated from the ethanolic extract of the fruits of Terminalia chebula Retz. by consecutive solvent partitioning, followed by silica gel and Sephadex LH-20 column chromatographies. The purified compound was identified as a mixture of chebulic acid and its minor isomer, neochebulic acid, with a ratio of 2:1 by spectroscopic analysis including 1D and 2D NMR and MS spectroscopy. To our knowledge, this is the first report on the protection of rat hepatocytes against oxidative toxicity by chebulic acid obtained from T. chebula Retz. This compound exhibited in vitro a free radical-scavenging activity and ferric-reducing antioxidant activity. Also, the specific ESR spectrum for the ^•OOH radical signals consisting of three-line ESR spectra was within the field of 0.27 mT, whereas 2.5 and 0.25 mg/ml of chebulic acid significantly reduced the signal intensity of the ESR spectra to 0.06 mT and 0.11 mT, respectively. Using isolated rat hepatocyte experiment, we demonstrated that the treatment of hepatocytes with chebulic acid significantly reduced the tert-butyl hydroperoxide (t-BHP)-induced cell cytotoxicity, intracellular reactive oxygen species level, and the ratio of GSSH, oxidized form of glutathione (GSH) to the over total GSH (GSH + GSSG) (4.42%) as compared to that with t-BHP alone (8.33%).     

The role of vitamin C as antioxidant in protection of oxidative stress induced by imidacloprid

Pesticides may induce oxidative stress leading to generate free radicals and alternate antioxidant or oxygen free radical scavenging enzyme system. This study was conducted to investigate the acute toxicity of imidacloprid toward male mice and the oxidative stress of the sublethal dose (1/10 LD₅₀) on the lipid peroxidation level (LPO), reduced glutathione content (GSH) and activities of the antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), and glutathione-s-transferase (GST). Also, the protective effect of vitamin C (200 mg/kg bw) 30 min before or after administration of imidacloprid were investigated. The results demonstrated that the median lethal dose (LD₅₀) of imidacloprid after 24 h was 149.76 mg/kg bw. The oral administration of 14.976 mg/kg imidacloprid significantly caused elevation in LPO level and the activities of antioxidant enzymes including CAT, SOD, GPx and GST. However, G6PD activity remained unchanged, while the level of GSH content was decreased. In addition, the results showed that vitamin C might ameliorate imidacloprid-induced oxidative damage by decreasing LPO and altering antioxidant defense system in liver. The protective effect of the pre-treatment with vitamin C against imidacloprid-induced oxidative stress in liver mice is better than the post-treatment.     

Activity and gene expression profile of certain antioxidant enzymes to microcystin-LR induced oxidative stress in mice

Microcystins are cyclic heptapeptide toxins produced by certain strains of Microcystis aeruginosa and microcystin-LR (MC-LR) is the most toxic among the 70 variants isolated so far. These toxins have been implicated in both human and livestock mortality. In the present study we investigated the microcystin-LR induced oxidative stress in mice in terms of its effect on activity and gene expression profile of certain antioxidant enzymes and expression of heat shock protein-70 (HSP-70). Mice were treated with 0.5 LD₅₀ (38.31 μg/kg) and 1 LD₅₀ (76.62 μg/kg) and the biochemical variables were determined at 1, 3, 7 days and 15, 30, 60 and 120 min post-exposure for 0.5 and 1 LD₅₀ dose, respectively. A significant time-dependent increase in HSP-70 expression over control was observed at 1 LD₅₀ dose. The toxin induced significant increase in liver body weight index, hepatic lipid perxoidation and depletion of GSH levels at 1 LD₅₀ compared to control group. There was significant decrease in the activity of antioxidant enzymes glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione-S-transferase (GST) at 1 LD₅₀. Except catalase, there was no effect on other antioxidant enzymes at 0.5 LD₅₀ dose. In contrast to activity of antioxidant enzymes the gene expression profile did not show any significant difference compared to control at 1 LD₅₀. GR showed significant decrease in expression at 1, 3 and 7 days in animals dosed with 0.5 LD₅₀ MC-LR. The results of our in vivo study clearly show the oxidative stress induced by MC-LR, and a correlation with activity and regulation at gene expression level of antioxidant enzymes.     

Effects of d-amphetamine and cocaine on repeated acquisition with timeout from avoidance

The acute effects of d-amphetamine and cocaine on a repeated acquisition baseline with timeout from avoidance were investigated in two rats. Each session the animals acquired one of two different three-member response sequences. Each sequence member was associated with a different response lever. The first two correct responses of each sequence postponed shock for a fixed period of time. The third correct response initiated a signalled timeout (30 sec) from avoidance. Incorrect responses did not postpone shock. The baseline performance was characterized by a decrease in errors within each session, similar to patterns of repeated acquisition maintained by food. In comparison to control sessions, both d-amphetamine and cocaine increased errors and altered the pattern of within-session acquisition. d-Amphetamine increased the rate of sequence completion and the rate of shock delivery in both animals. Cocaine increased the rate of sequence completion in one animal and increased the rate of shock delivery for the other.     

Effect of repeated administration of 4-methylpyrazole on renal function and lipid peroxidation products in rat kidney after ethylene glycol poisoning

Toxic effects of ethylene glycol (EG) and its metabolites are mainly related to metabolic acidosis and kidney damage. EG biotransformation involving CYP2E1 affects the oxidant-antioxidant balance. The study assessed the effect of repeated administration of 4-methylpyrazole (4MP, 15 mg/kg b.w. after 2 h, followed by 10 mg/kg b.w. every 12 h) on renal function (creatinine, urea and urinary protein levels) as well as products of kidney’s lipid peroxidation (MDA and TBARS levels) in rats poisoned with EG (5745 mg/kg b.w.). Serum EG and glycolic acid (GA) concentrations were measured throughout the experiment. Repeated administration of 4MP reduced the rate of EG elimination, extended the period of EG persistence in serum and significantly limited formation of GA. The study showed the temporary intensification of kidney oxidative processes that correlated with changes in kidney function. It was found that the use of 4MP in EG poisoning inhibited its biotransformation to toxic metabolites, but simultaneously intensified oxidative damages in kidneys.     

Effects of insecticides fenitrothion,endosulfan and abamectin on antioxidant parameters of isolated rat hepatocytes

Fenitrothion, endosulfan and abamectin are insecticides that affect various organs in humans and animals. The present study was conducted to investigate their cytotoxicity in isolated male rat hepatocytes. The study suggests that incubation of hepatocytes with 10 or 100 μM of each insecticide for 2 h significantly decreased the cell viability. Increased leakage percentage of lactate dehydrogenase (LDH), alanine transaminase (ALT) and aspartate aminotranferase (AST) were detected in hepatocytes due to the same dose of insecticide exposure confirmed membrane damage of hepatocytes. Fenitrothion (100 μM) increased the cellular lipid peroxidation (LPO) levels more than the other insecticides. The activities of the antioxidant enzymes like superoxide dismutase (SOD), glutathione peroxidise (GSH-Px) and glutathione-S-transferase (GST) were decreased by fenitrothion incubation more than endosulfan and abamectin. The same treatment reduced the level of antioxidant glutathione (GSH) and increased the level of LPO. The activities of glutathione-S-transferase (GST) and gamma glutamyl transpeptidase (γ-GT) were more affected by fenitrothion and endosulfan, respectively, indicating an oxidative stress. There was negative correlation coefficient among GSH, GST and γ-GT. A significant correlation was also found between γ-GT and cell viability. The present study revealed that fenitrothion showed varying pathological signs depending on the dose; high dose caused marked damage of isolated hepatocytes in the oxidative and antioxidant parameters. Endosulfan induced cell membrane damage of the hepatocytes more than abamectin and fenitrothion as indicated by increasing the leakage percentages of LDH, ALT, AST and γ-GT. Therefore, hepatotoxicity of insecticides increased in a time and dose-dependent manner and depended on the class of the insecticide.     

Long-term administration of d-amphetamine: progressive augmentation of motor activity and stereotypy

The competitive relationship between d-amphetamine induced stereotypy and locomotor activity indicates the importance of their concurrent evaluation, especially during chronic studies. Repeated injection of 0.5, 1.0, 2.5, 5.0, or 7.5 mg/kg d-amphetamine for 36 successive days, in rats continuously exposed to the experimental chambers, produced a progressive augmentation in stereotypy and/or locomotion (depending on dose) during the 3–4 hr interval following injections (post-injection phase). In contrast, dark phase locomotor activity (8–20 hr after each daily injection) was maximally reduced (30–40% of controls) after the first injection of either 5.0 or 7.5 mg/kg d-amphetamine and gradually declined to this level with repeated injection of 1.0 and 2.5 mg/kg. Carry-over of both the post-injection augmentation and dark phase reduction of locomotion was revealed during amphetamine retest 8 days following discontinuation of daily d-amphetamine injections. Possible mechanisms underlying these behavioral alterations are discussed.     

Assessment of red onion on antioxidant activity in rat

Oxidative stress related to the aging process can increase the risk of degenerative disease. Red onions contain antioxidative compounds. This study was designed to investigate the effect of dietary red onion peel and/or flesh on antioxidative activity in rats. Twenty Sprague–Dawley male rats (18 weeks old) were divided into four groups. Each group was raised for 4 weeks on a red onion free control diet (ND), red onion diet containing 5% red onion peel (RP), 5% red onion flesh (RF), or 5% red onion peel + flesh (RPF). The results demonstrated that serum SOD activity was significantly increased in the RP and RPF groups, whereas glutathione peroxidase (GPx) activity was significantly higher in the RF group than in the ND group. Catalase activity and ORAC activity in liver showed upward tendency in the RP, RF, and RPF groups although the differences were not statistically significant. Liver malondialdehyde levels in the RPF group were significantly lower than those in the ND group were. In conclusion, red onion may enhance antioxidant defense mechanism through the induction of plasma SOD and GPx activities and inhibited liver lipid peroxidation. Therefore, red onion may exert important protective effects against oxidative stress related diseases.     

Effects of the anticancer dehydrotarplatin on cytochrome P450 and antioxidant enzymes in male rat tissues

The effect of dehydrotarplatin (DTP), a new antineoplastic drug analogous to cisplatin, and its metabolite (Triacid) on the hepatic, renal and testicular CYP and antioxidant enzymes of male rats was investigated. The rats were treated i.p. with a single dose of DTP (25 mg kg⁻¹ day⁻¹) or Triacid (17.5 mg kg⁻¹ day⁻¹) and analysed 3 or 7 days post treatment. Three days after treatment, both drugs reduced body and liver weights, which partially recovered the control level after 7 days. DTP and, to a less extent, Triacid caused a depletion of plasmatic testosterone content and a down regulation in the liver of androgen dependent male specific CYP 2C11, but not of CYP 1A and 2E1, as determined by a significant decrease of 2α- and 16α-testosterone hydroxylase activities (markers for CYP 2C11) and of apoprotein immunoreactive with anti-rat CYP 2C11 antibodies. However, the activity of testicular 17α-progesterone hydroxylase, a key reaction in steroidogenesis, was not altered by these drugs. The DTP and Triacid administration did not cause any alteration of the plasmatic urea nitrogen and creatinine, known as markers of kidney toxicity. However, treatment with DTP, not Triacid, either 3 and 7 days post treatment, caused in the kidney microsomes a significant increase of the total CYP content, the CYP 4A-dependent (ω)- and (ω − 1)-lauric acid hydroxylase activities and apoprotein immunoreactive with anti-rat CYP 4A1. The present study also examined the enzymatic antioxidant status of kidney and liver. Neither DTP nor Triacid administration induced, with respect to control values, any alteration of hepatic and renal glutathione reductase, glutathione S-transferase, catalase, superoxide dismutase activities, hepatic GSH level and renal microsomal lipid peroxidation level. Among the antioxidant enzymes assayed, only the renal activity of glutathione peroxidase was significantly increased after DTP but not Triacid treatment. These results indicate that DTP at a dose of 25 mg/kg and Triacid cause a feminization of the CYP enzymes in male rat liver similar to that reported for cisplatin when administered at a low dose (5 mg/kg). However, unlike cisplatin, DTP and its metabolite were unable to enhance BUN and creatinine and cause any depression of CYP activities and antioxidant enzymes in the kidney, suggesting that DTP may have low or even no potential in inducing nephrotoxicity.     

Mitigating role of quercetin against sodium fluoride-induced oxidative stress in the rat brain

Context: Quercetin is a well known aglycone flavonoid that is widely found in different food sources.

Objective: In this study, the in vivo neuroprotective potential of quercetin against sodium fluoride-induced oxidative stress was evaluated.

Materials and methods: Wistar rats were divided into five treatment groups and then subjected to daily intraperitoneally treatment with quercetin (at 10 and 20?mg/kg body weight), vitamin C (at 10?mg/kg), or vehicle. After a 1 week treatment period, all groups except saline treated (normal group), were intoxicated with sodium fluoride (NaF) for 1 week. Rat brains were then removed and homogenized for measurement of antioxidant markers including superoxide dismutase (SOD), reduced glutathione, catalase, and lipid peroxidation final products.

Results: The thiobarbituric acid reactive substances (TBARS) levels in the heart homogenate of sodium fluoride treated rats (42.04?±?2.14 nmol MDA eq/g tissue) increased compared to the normal rats (35.99?±?1.08 nmol MDA eq/g tissue). Animals which were pretreated with quercetin at 20?mg/kg for 1 week prior to sodium fluoride intoxication showed significant reduction in the TBARS level (36.13?±?1.12 nmol MDA eq/g tissue). Also, pretreatment with quercetin (20?mg/kg) restored the SOD and catalase activities and modified the level of reduced glutathione compared with the control group (p?>?0.05).

Discussion and conclusion: The present study revealed a potent neuroprotective potential of quercetin against NaF-induced toxicity.     

Effect of neuroleptics and of combinations of d-amphetamine and neuroleptics on 3H-dopamine uptake by homogenates from rat striatum

Triperidol was found to be a more potent ³H-dopamine uptake inhibitor than chlorpromazine in homogenates from rat striatum. Inhibition kinetics were competitive for triperidol and non-competitive for chlorpromazine. When drugs were given in vivo, d-amphetamine (10 mg/kg) blocked the ³H-dopamine uptake by about 50% whereas the neuroleptics did not modify the process even at highly sedating doses. Combined treatments with d-amphetamine and neuroleptics showed that only triperidol potentiated the blocking effect of d-amphetamine on ³H-dopamine uptake. However, such a potentiation was not observed when triperidol and d-amphetamine were simultaneously added in vitro. The results tend to suggest that the postulated actions of neuroleptics on presynaptic sites in the striatum may be more important with the butyrophenone, triperidol than with the phenothiazine, chlorpromazine.