Fluoride-induced brain damages in suckling mice

In order to reveal mechanisms of brain damages resulted from fluoride toxicity, we treated adult female mice of Swiss Albinos strain by 500 ppm NaF (226 ppm F⁻) in their drinking water from the 15th day of pregnancy until the day 14 after delivery. All mice were sacrificed on day 14 after parturition. During treatment, levels of thiobarbituric acid reactive substances (TBARS), the marker of lipid peroxidation extend, increased, while the activities of the antioxidant enzymes such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), and the level of glutathione (tGSH) decreased significantly in both cerebellum and cerebrum compared with those of the control group. These results suggested that fluoride enhanced oxidative stress in the brain, thereby disturbing the antioxidant defense of nursing pups. In addition, acetylcholinesterase (AChE) activity in both cerebellum and cerebrum was inhibited after treatment with fluoride. In our previous studies we have found, a decrease in plasma thyroid hormone levels of nursing pups whose mothers were treated by NaF. In cerebellum of mice, migration of neurons from the external granular layer to the internal granular layer occurred postnatally and was dependent upon the presence of thyroid hormone. In hypothyroidism, several neurons failed to complete their migration and died. Key guidance signals to these migrating neurons were provided by laminin, an extracellular matrix protein fixed to the surface of astrocytes. In the present study we examined the expression and distribution of laminin in cerebellum of 14-day-old mice. Immunoreactive laminin was disappeared by postnatal day 14 in cerebellum parenchyma of control pups and was restricted to vasculature despite the continued presence of granular cells in the external granular layer. In contrast, in cerebellum of NaF treated pups, laminin was deposited in organised punctuate clusters in the molecular layer. These data indicated that the disruption of laminin distribution might play a major role in the profound derangement of neuronal migration observed in cerebellum of NaF treated pups.     

Oxidative damage in bone and erythrocytes of suckling rats exposed to 2,4-dichlorophenoxyacetic acid

Nowadays, people’s exposure to pesticides such as 2,4-dichlorophenoxyacetic acid (2,4-D) is increasing continuously. This compound is suspected to produce in excess free radicals which have adverse effects on human health causing several cell alterations in the organism. The present study investigated oxidative stress in the bone and erythrocytes of suckling rats whose mothers were treated with 2,4-D. Experiments were carried out on adult Wistar rats given 600 mg/L of 2,4-D in their drinking water from the 14th day of pregnancy until day 14 after delivery. Exposing dams to 2,4-D caused disorders in the bone of their progeny. Indeed, it induced changes in bone mineralization, especially calcium and phosphorus levels. Moreover, total tartrate-resistant acid phosphatase, which reflected bone resorption, was enhanced while total alkaline phosphatase, which reflected bone formation, was reduced suggesting that this herbicide accelerated bone resorption. The impairment of bone function corresponded histologically.Rats exposed to 2,4-D showed in both bone and erythrocytes an increase in malondialdehyde, advanced oxidation protein products and protein carbonyl levels and a decrease in non-enzymatic (glutathione, non-protein thiol, and vitamin C) and enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) antioxidant system.     

Dimethoate induced biochemical perturbations in rat pancreas and its attenuation by cashew nut skin extract

The significant antiradical activity of cashew skin extract was previously described. In this investigation, the extent of protection offered by cashew nut skin extract (CSE) against the damage induced in rat pancreas by sub chronic doses dimethoate (DM), an organophosphorous pesticide was studied. Rats were supplemented with CSE at 20 mg/kg b.w./d after a daily dose of DM at 40 mg/kg/d b.w. for 2 months. Weekly random blood glucose, oral glucose tolerance test (OGTT); pancreatic damage markers like amylase and lipase; oxidative damage markers such as reactive oxygen species generated, extent of lipid peroxidation, host antioxidant defenses like reduced glutathione (GSH); GSH-dependent enzyme activities viz., glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR); free radical scavenger enzymes viz., catalase and superoxide dismutase (SOD); xenobiotic metabolizing enzymes like DT-diaphorase and NADPH-diaphorase were measured in the four different groups namely (1) control, (2) DM treated, (3) CSE supplemented, (4) CSE supplements following DM treatment. Random blood glucose levels increased significantly on exposure to DM compared to that in control rats (119 ± 5 mg/dl vs. 92 ± 4 mg/dl), while the blood glucose levels in CSE supplemented rats were comparable to that of controls. DM treated rats exhibited impaired glucose tolerance at the end of two months as indicated by OGTT, while DM treated rats with CSE supplements showed normal glucose tolerance. Pancreatic specific marker enzymes like amylase and lipase in serum were restored to normalcy in rats supplemented with CSE following treatment with DM which otherwise was increased in the DM treated rats. Distinctly lower levels of GSH, increased levels of ROS, higher extent of lipid peroxidation, along with alterations in antioxidant enzymes and increase in xenobiotic metabolizing enzymes were evident in pancreas of DM treated rats. However, CSE supplement ameliorated the biochemical alterations in the pancreatic milieu in DM treated rats. Treatment with CSE significantly protected rat pancreas from injury, thus ameliorating and restoring tissue antioxidant status and also conferring normal glucose tolerance. The active components present in cashew skin extract can perhaps be effective in reducing the extent of pancreatic injury and in overcoming tissue damage caused by exposure to dimethoate.     

Chlorpyrifos-induced oxidative stress and histological changes in retinas and kidney in rats: Protective role of ascorbic acid and alpha tocopherol

This study was undertaken to evaluate the antioxidant effect of vitamins C and E against oxidative stress, apoptosis and histological changes of kidney and retina in CPF-treated rats. Forty male Sprague-Dawley rats were divided into four groups including the control group, the group treated orally with a single dose of CPF (63 mg/kg b.w.), the group injected intramuscularly (i.m.) with vitamin C (250 mg/kg b.w.), and intraperitonealy (i.p.) with vitamin E (150 mg/kg b.w.) daily for 7 days and the group treated with CPF (single dose) and injected with vitamins (for 7 days). The results showed that CPF induced apoptosis and severe oxidative stress as indicated by the significant increase in MDA and sFasL concentration and the significant decrease in GSH concentration in serum. Co-administration of vitamins C and E ameliorate these toxic effects and improved the histological pictures of kidneys and retinas. It could be concluded that combined administration of vitamins C and E is useful in the routine therapy for the protection against tissue damage induced by CPF.     

Methyl parathion induced nephrotoxicity in male rats and protective role of vitamins C and E

Methyl parathion is an organophosphate insecticide that has been used in agriculture and domestic for several years. Vitamin C (200 mg/kg bw per day) + vitamin E (200 mg/kg bw per day), methyl parathion (0.28 mg/kg bw per day) and vitamin C (200 mg/kg bw per day) + vitamin E (200 mg/kg bw per day) + methyl parathion (0.28 mg/kg bw per day) combination were given to rats orally via gavage for 7 weeks. Body and kidney weights, malondialdehyde (MDA) levels and histopathological changes were investigated at the end of 4th and 7th weeks comparatively with control group. When methyl parathion-treated group and vitamins C and E + methyl parathion-treated group were compared to control group body and kidney weights decreased significantly at the end of 4th and 7th weeks. MDA levels increased in kidney tissues of the methyl parathion- and vitamins C and E + methyl parathion-treated groups compared to control group. MDA levels decreased significantly in vitamins C and E + methyl parathion treated group compared with methyl parathion treated group at the end of 4th and 7th weeks. In our light microscopic investigations, after 4 weeks of methyl parathion exposure, glomerular atrophy and vascular dilatation, and after 7 weeks, necrosis and edema were observed in the kidney tissues. After 4 weeks of vitamins C and E + methyl parathion exposure, mononuclear cell infiltrations, and after 7 weeks, calcification were detected in the kidney tissues.     

Effects of sodium fluoride on hepatic toxicity in adult mice and their suckling pups

In this investigation, we have evaluated the effect of sodium fluoride (NaF) on hepatic function in pregnant and lactating mice and their suckling pups. Experiments were carried out on female Wistar mice given 500 ppm sodium fluoride (226 ppm fluoride ion) in their drinking water from the 15th day of pregnancy until day 14 after delivery. All mice were sacrificed on day 14 after parturition. Our results showed a significant decrease in serum levels of total protein and albumin, a marked hypoglycaemia and a significant decline in serum cholesterol and triglyceride levels in fluoride-treated mice and their pups. Whereas globulin and biluribin levels in serum were not significantly changed by NaF treatment. On the other hand, serum transaminase activities (aspartate transaminase; alanine transaminase), which well known as markers of liver function, were elevated indicating hepatic cells’ damage after treatment with fluoride. Lipid peroxidation increased in NaF-treated mice and pups, as revealed by high liver malondialdehyde levels, while serum total antioxidant status showed a significant decline. These biochemical modifications in NaF-treated mice also correspond histologically with extensive ballooning, hepatocellular necrosis and infiltration of mononuclear cells. These effects were not observed in controls.     

Oxidative damage, biochemical and histopathological alterations in rats exposed to chlorpyrifos and the antioxidant role of zinc

The protective effects of zinc on liver and kidney injury induced by chlorpyrifos (CPF) were investigated in rats. Male and female rats were orally administered CPF at a dose of 6.75 mg kg⁻¹ body weight for 28 consecutive days. An additional CPF group received zinc (227 mg l⁻¹) in drinking water throughout the experimental duration. Two groups more served as controls. Administration of CPF resulted in a significant increase in serum lipid peroxidation (LPO) level, while induced significant decreases in the activities of plasma superoxide dismutase (SOD), glutathione-S-transferase (GST) and serum acetylcholinesterase (AChE) either in male or female rats. Similarly, a significant increase in the levels of various serum marker enzymes [e.g. aminotransferases (AST and ALT), lactate dehydrogenase (LDH) and gamma glutamyl transferase (GGT)] and increase the level of total protein, uric acid and creatinine. In contrast, co-administration of zinc to CPF-treated animals restored most of these biochemical parameters to within normal levels. In case of AChE, supplementation of zinc showed little alteration in the activity of this enzyme especially in male rats treated with CPF. CPF caused histopathological change in liver and kidneys of male and female rats. However, zinc administration to CPF-treated animals resulted in overall improvement in liver and kidneys damage, emphasizing its antioxidant role. In light of the available data, it can deduce that CPF-induced lipid peroxidation, oxidative stress, liver and kidneys damage in male and female rats, and conjunction supplementation of zinc has resulted in pronounced ameliorating effect.     

氯吡脲连续灌胃给药4周对大鼠的毒性作用

为明确氯吡脲对大鼠的毒性作用,采用150、300和600 mg/kg剂量分别向SD大鼠灌胃 (ig) 给予氯吡脲,每日1次,连续给药4周。每日观察大鼠的中毒状况和死亡情况,每周记录体质量和摄食量;于停药后第1天和第15天分别处死SD大鼠,检测血常规、血清生化和凝血功能;取主要脏器进行称量,计算其脏器系数并进行常规病理组织学检查。结果发现:连续给药4周,氯吡脲对大鼠体质量、摄食量、血常规和凝血均无明显影响。停药后第1天,与溶剂对照组比较,氯吡脲300 mg/kg及以上剂量处理组雄性大鼠的尿素氮和肌酐含量明显升高 (P < 0.05),600 mg/kg剂量组血糖显著升高 (P < 0.05),其中,600 mg/kg处理组雄性大鼠的尿素氮、肌酐和血糖分别是对照的1.9、1.6和1.3倍。氯吡脲300 mg/kg及以上剂量组雌、雄性大鼠的肾脏系数均明显升高 (P < 0.05),其中300 mg/kg剂量组雌、雄性大鼠的肾脏系数分别是对照的1.2和1.1倍,600 mg/kg剂量组雌、雄性大鼠的肾脏系数分别是对照的1.4和1.1倍;300 和600 mg/kg剂量组雌性大鼠的肝脏系数明显升高 (P < 0.01),分别是对照的1.3和1.9倍。病理切片检查可见肾脏病理组织学改变,主要表现为轻度肾管萎缩,明显的白细胞管型、透明管型、间质炎性细胞浸润及肾小管扩张。停药后第15天,上述毒性反应症状有所恢复。研究表明,SD大鼠经连续灌胃给予氯吡脲4周,在600 mg/kg剂量下表现为明显肾脏毒性反应,在300 mg/kg剂量下表现为较轻微的肾脏毒性反应,推测氯吡脲的主要毒性靶器官可能是肾脏;其未见明显毒性反应剂量为150 mg/kg。     

Nephrotoxicity in rats induced by organophosphate insecticide methidathion and ameliorating effects of vitamins E and C

The effects of organophosphate insecticide methidathion (MD) on kidney tissue and the ameliorating effects of a combination of vitamins E and C against subchronic MD toxicity were evaluated in rats. Experimental groups were: control group (group I), 5 mg/kg body weight MD-treated group (group II), and 5 mg/kg body weight MD plus vitamin E plus vitamin C treated group (group III). The groups II and III were treated orally with MD on five days a week for four weeks. Vitamins E and C were injected at doses of 50 mg/kg body weight, i.m. and 20 mg/kg body weight, i.p., respectively, 30 min after the treatment of MD in the group III. Rats were anaesthesized and venous blood samples were collected by direct right ventricle heart puncture, in addition, the right kidney was removed for histopathological examinations and malondialdehyde (MDA) analyses after four weeks. The serum activity of cholinesterase (ChE) and the kidney level of malondialdehyde, and kidney histopathology were studied in rats. MD caused decreased ChE activity (group I: 2114 ± 63 U/L, group II: 1455 ± 100 U/L) and increased MDA level (group I: 147 ± 20.2 nmol/mg protein, group II: 236 ± 25.6 nmol/mg protein), and kidney damage in rats. Furthermore, a combination of vitamins E and C restored partially (ChE activity: 1670 ± 111 U/L, MDA level: 159 19.4 nmol/mg protein) this changes in MD-treated rats.     

Ameliorative effect of lycopene on antioxidant status in Cyprinus carpio during pyrethroid deltamethrin exposure

The aim of the present study was to investigate the ameliorative properties of lycopene against the toxic effects of deltamethrin (DM) by examining oxidative damage markers such as lipid peroxidation and the antioxidant defense system components in carp (Cyprinus carpio). The fish were divided into seven groups of 15 fish each and received the following treatments: Group 1, no treatment; Group 2, orally administered corn oil; Group 3, oral lycopene (10 mg/kg body weight); Group 4, exposure to 0.018 μg/L DM; Group 5, exposure to 0.018 μg/L DM plus oral administration of 10 mg/kg lycopene; Group 6, exposure to 0.036 μg/L DM; and Group 7, exposure to 0.036 μg/L DM plus oral administration of 10 mg/kg lycopene. Treatment was continued for 14 days, and at the end of this period, blood and tissue (liver, kidney, and gill) samples were collected. Levels of malondialdehyde (MDA) and reduced glutathione (GSH) as well as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were determined in blood and tissues for measurement of oxidant-antioxidant status. A significant elevation in the level of MDA, as an index of lipid peroxidation, and reductions in antioxidant enzyme activities (SOD, CAT, and GSH-Px) and low molecular weight antioxidant (GSH) levels were observed in DM-exposed fish. Treatment with lycopene attenuated the DM-induced oxidative stress by significantly decreasing the levels of MDA. In addition, lycopene significantly increased the SOD, CAT, and GSH-Px activities and the level of GSH. The present results suggest that administration of lycopene might alleviate DM-induced oxidative stress.     

Prophylactic effect of green tea polyphenols against liver and kidney injury induced by fenitrothion insecticide

The ameliorative effect of daily administrated dose of green tea extract (60 mg polyphenols/animal/day) was investigated on albino rats Rattus norvegicus (150-180 gm) intoxicated with 1/30 and 1/60 LD₅₀ fenitrothion organophosphate insecticide for 28 days. Blood samples were taken at 14 and 28 days for further biochemical parameters. Histopathological studies were carried out in the liver and kidney at the end of the experiment. Significant inhibition in plasma cholinesterase (ChE), a biomarker of Ops, was recorded. Damage in the liver and kidney tissues was observed and confirmed with elevation of plasma alanine aminotransferase (ALT), aspartate aminotaransferase (AST), albumin, urea and creatinine, as well as an elevation in the oxidative stress (OS) marker malondialdehyde (MDA). Decrease in total glutathione (GSH) content in erythrocytes and fluctuation in glutathione S-transferase (GST) activity in plasma was also observed. Green tea supplementation (60 mg/animal/day) partially counteracts the toxic effect of fenitrothion on oxidative stress parameters and repairs tissue damage in the liver and kidney, especially when supplemented to 1/60 LD₅₀ intoxicated animals depending on the duration. It seems that enzyme and metabolite markers of these organs need more time to be restored to the control level.     

A two generation chronic mixture toxicity study of Clophen A60 and diethyl phthalate after gestational and lactational exposure in female Wistar rats

Polychlorinated biphenyls and diethyl phthalate are both lipophilic in nature and are likely to be present in the same environmental compartment or bioaccumalate over a period of time, thus a mixture toxicity study was undertaken to evaluate the type of interaction between polychlorinated biphenyls (Clophen A60) and diethyl phthalate over two generations in female Wistar rats. Healthy male and female albino rats of Wistar strain weighing 75-100 g (6-7 weeks old) were randomly assigned to four groups of six each. Group I male and female rats were fed on normal diet and water ad libitum. Group II male and female rats were maintained on normal diet mixed with corn oil as oil control. GroupS III and IV male and female rats were given Clophen A60 and diethyl phthalate dissolved in corn oil mixed with the diet at 50 mg/kg of the diet individually to each group. Group V male and female rats received a mixture of diethyl phthalate and Clophen A60, each dissolved in corn oil mixed with the diet at 50 mg/kg of the diet. Hundred days after the treatment, females were mated with the males in each group for 10 days. Exposure to diethyl phthalate and Clophen A60 was continued throughout mating, gestation until termination at weaning, which was 150 days of total treatment period of the parental generation female rats. Treatment for F1 generation male and female pups (6 males & 6 females) with Clophen A60 and diethyl phthalate individually and in mixture was continued at doses reduced to 25 mg/kg of the diet after they reached 75-100 g in weight. The treatment was carried out similar to the parental generation for a period of 150 days. Liver and serum aspartate aminotransferase, liver cholesterol and glycogen were significantly increased in the F1 generation Clophen A60 + diethyl phthalate treated group, whereas serum cholesterol, liver glutathione and glutathione reductase showed a significant decrease in the F1 generation Clophen A60 + diethyl phthalate treated group as compared to the parental generation mixture and individually treated groups as well as the individually treated F1 generation groups. A significant increase was observed in the liver and serum aspartate aminotransferase activity of Clophen A60 and serum aspartate aminotransferase levels of diethyl phthalate treated F1 generation rats as compared to the parental generation Clophen A60 and diethyl phthalate individually and mixture treated rats. Liver glutathione levels were significantly decreased in the F1 generation Clophen A60 and diethyl phthalate individually treated rats which was similar to the parental generation individually treated rats as compared to the controls. Liver glutathione reductase level was also significantly declined in the diethyl phthalate treated F1 individual group as compared to diethyl phthalate individually treated parental generation rats. Histology of the liver showed fatty degeneration in the mixture treated F1 generation rats as compared to Clophen A60 and diethyl phthalate individually treated F1 rats and parental generation Clophen A60 and diethyl phthalate individually and mixture treated rats. Thus, in spite of dose reduction and continuous exposure over two generation’s to a mixture of diethyl phthalate and Clophen A60 exposed through gestation, lactation and diet leads to a synergistic toxic effect in the F1 generation.     

Modulation of ethion-induced hepatotoxicity and oxidative stress by vitamin E supplementation in male Wistar rats

Organophosphorus insecticides (OPIs) may induce oxidative stress leading to generation of free radicals and alteration in antioxidant system of animals. Many studies reported that enzymatic and non-enzymatic antioxidant may play protective role against OPIs induced toxicity in human and rats. The aim of present study was to investigate the possible protective role of vitamin E on ethion-induced hepatotoxicity in rats using qualitative, quantitative and biochemical approaches. Adult male albino rats of Wistar strain were randomly divided into four groups; each group consists of six animals. Animals were treated for a period of 28 days. Group I (control group received corn oil); Group II [ethion treated (2.7 mg/kg bw/day)]; Group III (vitamin E treated (50 mg/kg of bw/day)]; Group IV (ethion + vitamin E treated). Animals were sacrificed after 7, 14, 21 and 28 days by decapitation and liver tissue was used for the measurement of proteins, lipid peroxidation (LPO), reduced glutathione (GSH) content and activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) glutathione reductase (GR) and glutathione-S-transferase (GST). Erythrocytes were analyzed for acetyl cholinesterase activity. The result of this study shows that in vivo administration of ethion caused a significant induction of oxidative damage in liver tissue as evidenced by increased level of LPO and decreased GSH content. Ethion toxicity also led to a significant increase in the activities of SOD, CAT, GPx and GST in liver tissue. In addition, decrease in GR activity was observed in ethion administered rats compared to control. Histopathological findings revealed that exposure to ethion caused damage in liver tissue. However, simultaneous supplementation with vitamin E restored these parameters partially. In conclusion, the results of the current study revealed that ethion-induced toxicity caused lipid peroxidation, alterations in the antioxidant enzymes and histopathological changes in liver. Supplementation of vitamin E exhibited protective effect by inhibiting ethion-induced toxicity in liver and erythrocytes.     

Monocrotophos induced lipid peroxidation and oxidative DNA damage in rat tissues

Monocrotophos (dimethyl(E)-1-methyl-2-(methyl carbamoyl) vinyl phosphate, MCP), a substituted vinyl phosphate, is a potent systemic toxicant and used for control of variety of pests. The present study is undertaken to evaluate the genotoxic potential of monocrotophos and time-dependent repair of the damaged DNA in rats, using single cell gel electrophoresis or comet assay. The involvement of oxidative stress was also examined by estimation of thiobarbituric acid reactive substances (TBARS) in the tissues of MCP exposed rats. The rats were given oral exposure of 4.5 and 9 mg MCP/kg body weight once as well as 0.3 and 0.6 mg MCP/kg body weight for 60 days. A dose-dependent increase was recorded in the levels of TBARS in the liver, kidney, spleen and brain of MCP exposed rats. Cytotoxicity of MCP is evident from the histopathological studies of rat tissues. The level of DNA damage was estimated by scoring 50 cells per animal, dividing into five types, Types 0, I, II, III and IV. The results clearly indicated that exposure to MCP, acutely or chronically, caused a dose-dependent increase in the number of damaged nuclei of Types II, III and IV in the liver, kidney, spleen and brain of rats. When the DNA damage was studied 48 and 72 h post MCP treatment, a significant reduction in the number of types III and IV nuclei was observed in all the tissues indicating a time-dependent repair. From the present study, it can be concluded that oxidative stress may be involved in the toxicity of MCP and MCP induces DNA damage in all the rat tissues exhibiting genotoxic potential in vivo.     

Determination of toxicity of trichloroacetic acid in rats: 50 days drinking water study

This study aims to investigate the effects of the trichloroacetic acid (TCA) on serum marker enzymes [aspartate aminotransferase (AST), alanin aminotransferase (ALT), creatine phosphokinase (CPK), acid phosphatase (ACP), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)], antioxidant defense systems [Reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)] and lipid peroxidation content (Malondialdehyde, MDA) in various tissues of rats. TCA (2000 ppm) as drinking water was administered orally to rats (Sprague-Dawley albino) ad libitum for 50 days continuously. TCA treatments caused different effects on the serum marker enzymes, antioxidant defense systems and the MDA content in experimented rats compared to controls. Results showed that TCA caused a significant increase in serum AST, ALT, CPK and ACP activity. The lipid peroxidation end product MDA slightly increased in the erythrocytes, liver and kidney of rats treated with TCA, whereas did not change in the brain. In addition, antioxidant enzyme activity such as CAT and SOD significantly increased in the brain, liver and kidney tissues of TCA induced group whereas the ancillary enzyme GR and the drug metabolizing enzyme GST activity did not significantly change in the all tissues. The observations presented led us to conclude that the administration of subchronic TCA promotes lipid peroxidation content, elevates tissue damage serum marker enzymes and fluctuates in the antioxidative systems in rats. Also the rats resisted to oxidative stress via antioxidant mechanism but the antioxidant mechanism could not prevent the increases in lipid peroxidation in rat’s tissues. These data, along with the determined changes suggest that TCA produced substantial systemic organ toxicity in the erythrocyte, liver, brain and kidney during the period of a 50-day subchronic exposure.     

Coexpression with Auxiliary β Subunits Modulates the Action of Tefluthrin on Rat Na(v)1.6 and Na(v)1.3 Sodium Channels

The erythrocyte, due to its role as O₂ and CO₂ transporter, is under the constant exposure to reactive oxygen species and oxidative stress. The objective of this study was to investigate the ability of 2,4-D to induce oxidative stress in blood of male wistar rats. Rats were randomly divided into four groups: a control group and three treated groups receiving by gavage 15, 75 and 150 mg, respectively, of 2,4-D/kg/BW/day for 28 days. Results showed that 2,4-D caused significant negative changes in the investigated biochemical parameters. In fact, 2,4-D exposition strongly increases LDH, by contrast, there is a statistically significant decrease in Hgb levels. The malondialdehyde level was significantly increased in 2,4-D treated groups. Fatty acid composition of the erythrocytes was also significantly changed with 2,4-D exposure, in favor of the peroxidation of polyunsaturated fatty acids. Furthermore, antioxidant enzyme (SOD, CAT, GPx, and GR) activities in erythrocytes were significantly decreased. Thus, our results indicated the potential effects of 2,4-D to cause oxidative stress in rat erythrocytes. Therefore, at higher doses, 2,4-D may play an important role in the development of vascular disease via lipid peroxidation and oxidative stress.     

Effects of sodium fluoride on hepatic toxicity in adult mice and their suckling pups

In this investigation, we have evaluated the effect of sodium fluoride (NaF) on hepatic function in pregnant and lactating mice and their suckling pups. Experiments were carried out on female Wistar mice given 500 ppm sodium fluoride (226 ppm fluoride ion) in their drinking water from the 15th day of pregnancy until day 14 after delivery. All mice were sacrificed on day 14 after parturition. Our results showed a significant decrease in serum levels of total protein and albumin, a marked hypoglycaemia and a significant decline in serum cholesterol and triglyceride levels in fluoride-treated mice and their pups. Whereas globulin and biluribin levels in serum were not significantly changed by NaF treatment. On the other hand, serum transaminase activities (aspartate transaminase; alanine transaminase), which well known as markers of liver function, were elevated indicating hepatic cells’ damage after treatment with fluoride. Lipid peroxidation increased in NaF-treated mice and pups, as revealed by high liver malondialdehyde levels, while serum total antioxidant status showed a significant decline. These biochemical modifications in NaF-treated mice also correspond histologically with extensive ballooning, hepatocellular necrosis and infiltration of mononuclear cells. These effects were not observed in controls.     

May antioxidants status depletion by Tetradifon induce secondary genotoxicity in female Wistar rats via oxidative stress?

Tetradifon is a potent organochlorine acaricide with an estrogen-like structure. The wide spread use of this chemical is likely to pollute the environment. Only few studies have been reported for the evaluation of its short- and long-term toxic effects including genotoxicity and carcinogenicity and there have been conflicting results in in vitro and in vivo test systems. In this work, we have evaluated Tetradifon for its ability to induce genotoxic damages in female Wistar rats. A single cumulative dose of 2430 mg/kg BW was administrated orally for 12 female rats of 190 g BW during 12 weeks. Twelve additional rats, no treated, have served as control. Animals were sacrificed after 6 and 12 weeks of treatment. Genetic toxicity studies were conducted in rats bone marrow, by chromosomal aberrations (CAs) and sister-chromatid exchanges (SCEs) assays. The oxidative stress status of treated animals has been also evaluated by assessment of lipid peroxidation by measuring thiobarbituric acid reactive substances (TBARS). Some serum parameters: vitamins (A and E), triglyceride (TG) and total antioxidants status (TAS) were determined. Our results showed a significant increase in tissue TBARS concentrations in the two treated groups suggesting that Tetradifon induce an oxidative stress. Elsewhere, rats treated with Tetradifon exhibited a statistical decrease in serum level of vitamin E and a significant depletion of serum total antioxidant status. Whereas, in comparison to control rats, treated animal cells did not show a significant increase in either the frequency of SCEs or CAs. These results indicate that Tetradifon did not present direct genotoxic effect in female Wistar rats. But we suggest that its inducting of an oxidative stress may lead to indirect mutagenecity that should be evaluated by other series of in vivo genotoxicity assays as micronucleus test or comet assay.     

Effect of diethylstilbestrol concentration and duration of contact with nursing Levant voles,on the reproduction of their female offspring

A 5-minute contact of nursing mothers of the Levant vole,Microtus guentheri, with paper impregnated with a DES suspension in soybean oil (125 μg/cm² ) caused sterilization of 60% of the newborn female offspring. A 1-hour contact was sufficient to sterilize more than 90% of them. When the DES concentration was decreased to 1 μg/cm² only 44% of the newborn female offspring were sterile although their nursing mothers had been exposed to contact with the treated paper for a period of 2 hours. The concentration of 0.1 μg/cm² was totally ineffective in causing sterilization. Treatment of nesting material with DES offers a promising means of reproductive suppression in Levant voles.     

Effects of vitamin E and selenium on tissue bio-element status in organophosphate toxicity of rats

The present study was designed to investigate the effects of vitamin E (vit E), selenium (Se) and vit E + Se against organophosphate (OP) toxicity in tissues’ trace and major element levels and erythrocyte antioxidant enzyme activities of rats. Trace and major element concentrations in the tissues were measured by inductively coupled plasma-optical emission spectroscopy. Erythrocyte antioxidant enzyme activities were studied by using spectrophotometer. Antioxidant enzyme activities such as superoxide dismutase, glutathione peroxidase and catalase increased in the fenthion-treated groups (control) more than that of sham group subjects. Heart and pectoral muscle tissue Se and Zn concentrations in the control group were higher than sham group. However, jejunum, kidney, liver and pancreas Se and Zn concentrations in the control group were found to be lower than those in the sham group. The Mn concentrations in the all of the tissues were lower in the control group when compared with the sham group. Brain, heart, jejunum, kidney and pancreas Fe concentrations and heart, jejunum, liver, pectoral muscle and pancreas Cu concentrations were found to be lower in the control group. The treatment of vit E, Se and vit E + Se were increased bio-element levels in the many tissue. In conclusion, the results of the present study demonstrate that the tissue trace and major element concentrations and enzymatic antioxidant system were significantly affected OP toxicity. Furthermore, we have shown an association between bio-elements and antioxidant enzymes in OP toxicity. In addition, administration of vit E, Se and vit E + Se might regulate some trace and major element levels in the many tissues.