Hepatoprotective activity of 1-(4-(Dimethylamino)Benzylidene)-5-(2-Oxoindolin-3-ylidene) Thiocarbohydrazone in rats

The aim of the present study was to evaluate the hepatoprotective activity of 1-(4-(dimethylamino)benzylidene)-5-(2-oxoindolin-3-ylidene) thiocarbohydrazone, a novel isatin derivative against carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. Hepatic damage was induced by administration of CCl₄ (1 ml/kg, b.w., p.o.) in combination with liquid paraffin (1:1) as a single dose. The hepatotoxic rats were treated with test compound at doses of 50 or 100 mg/kg for three days and liver damage biomarkers, including activities of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), serum alkaline phosphatase (ALP), and levels of total serum bilirubin (TB) measured in blood samples. Results demonstrated that treatment with test compound at doses of 50 or 100 mg/kg to hepatotoxic rats produced a significant dose-dependent reduction of elevated SGOT, SGPT, ALP activities and TB levels indicating a hepatoprotective effect that was confirmed by histopathological examination of liver tissues. The study results confirmed the hepatoprotective activity of 1-(4-(dimethylamino)benzylidene)-5-(2-oxoindolin-3-ylidene) thiocarbohydrazone in rats.     

Disposition of bisphenol A in pregnant mice and fetuses after a single and repeated oral administration

The risk assessment of bisphenol A (BPA) on the development of offspring of humans is an important issue. There have been some reports on the fate of BPA in rodents, but information on the BPA level in fetal organs essential for the extrapolation to humans is inadequate. In the present study, we investigated the distribution pattern of ¹⁴C-BPA-derived radioactivity in fetal tissues following administration of 10?mg/kg ¹⁴C-BPA to the pregnant mice. The radioactivity was rapidly transferred through placenta and distributed to all fetal organs including reproductive organs and brains in a similar level. The concentration declined slowly compared with dams. Analysis of metabolites in fetuses showed that a fraction of BPA was unexpectedly large compared to the maternal blood. There was no clear effect of the fetal position in a uterus to influence the radioactivity concentration in whole fetuses. The dose dependence of pharmacokinetics should be recognized to extrapolate the pharmacokinetic result from animal experiments at high doses to humans at low doses. Similar experiments were conducted with an addition of two doses, 1 and 100?mg/kg, respectively. The pharmacokinetics seemed to be linear between 1 and 10?mg/kg, although at 100?mg/kg BPA was absorbed slowly and the radioactivity concentrations in fetuses were much higher than expected based on the linear dose dependence. Repeated doses were administered to pregnant mice since humans are exposed to BPA chronically. Radioactivity level in most of the fetal tissues on repeated administration was higher than single administration.     

Toxicity of Nerium oleander leaf extract in mice

Non-lethal dose of 70% ethanol extract of the Nerium oleander dry leaves (1000 mg/kg body weight) was subcutaneously injected into male and female mice once a week for 9 weeks (total 10 doses). One day after the last injection, final body weight gain (relative percentage to the initial body weight) had a tendency, in both males and females, towards depression suggesting a metabolic insult at other sites than those involved in myocardial function. Multiple exposure of the mice to the specified dose failed to express a significant influence on blood parameters (WBC, RBC, Hb, HCT, PLT) as well as myocardium. On the other hand, a lethal dose (4000 mg/kg body weight) was capable of inducing progressive changes in myocardial electrical activity ending up in cardiac arrest. The electrocardiogram abnormalities could be brought about by the expected Na+, K(+)-ATPase inhibition by the cardiac glycosides (cardenolides) content of the lethal dose.     

Microwave-assisted synthesized zinc nanoparticles attenuate cisplatin-induced testicular toxicity in mice

Abstract

The purpose of this study was to investigate the protective effects of zinc nanoparticles against cisplatin-induced testicular toxicity in mice. Zinc nanoparticles were produced by microwave-assisted synthesis using Lavandula vera extract as reducing agent. Single doses of cisplatin (7?mg/kg, intraperitoneally) and ZnSO₄ (10?mg/kg, orally), and various doses of zinc nanoparticles (10???50?mg/kg, orally) and vitamin E (100?mg/kg, interaperitoneally) were administered. The protective role of zinc nanoparticles was determined biochemically and histologically. Gradual reduction in malondialdehyde levels and elevation in glutathione levels and in the activities of superoxide dismutase and catalase upon administration of zinc nanoparticles were observed. The pathology of mice treated with cisplatin/vitamin E and cisplatin/zinc nanoparticles were apparently equal, but vitamin E treatment was more effective in lowering oxidative stress markers than zinc nanoparticles. These findings suggest that co-administration of zinc nanoparticles with cisplatin could prevent adverse effects on the male reproductive system via their potential antioxidant properties.     

Cybil induced hepatobiochemical changes in wistar rats

Cybil, 25%EC formulation of Cypermethrin, induces biochemical changes in the liver of wistar rats after oral intubation of the same at acute (one day) and subacute (7, 14 and 21 days) levels. The changes were tallied with the controls run simultaneously. LD50 of Cybil was estimated to be 622mg/kg body weight The acute dose is 80mg/kg body weight exposed for one day i.e. 24 hours and subacute dose is 4mg/kg body weight exposed for 7, 14 and 21 days. When compared with the control values, both the doses enhanced the level of glycogen, cholesterol, total lipid and acid phosphatase activities, while decreased activity of alkaline phosphatase. Alterations in glycogen, cholesterol, total lipid, acid phosphatase and alkaline phosphatase resulted in the impairement in liver physiology.     

Antioxidant role of ascorbic acid on oxidative stress induced by sub-acute exposure of lead and cypermethrin in erythrocytes of Wistar rats

This study aimed to evaluate the reparative potential of ascorbic acid (AA, 100 mg/kg, orally for 28 days) in sub-acute lead (Pb, 100 ppm in drinking water for 28 days) or cypermethrin (CPM, 50 mg/kg, orally in vehicle for 28 days) poisoning alone and as binary mixture on the basis of oxidative stress parameters in erythrocytes of Wistar rats. Both Pb and CPM produced significant increase in lipid peroxidation along with elevated glutathione-S-transferase and catalase activity individually but not as a binary mixture. Glutathione peroxidase activity was significantly increased but glutathione levels were significantly reduced irrespective of single or co-exposure while the activity of superoxide dismutase and erythrocytic protein content were not significantly affected. Co-exposure led to a comparatively lower level of oxidative stress than that induced by Pb or CPM alone indicating an antagonistic toxicodynamic profile in rat erythrocytes. Co-administration of AA along with Pb and/or CPM significantly restored the oxidative stress parameters to normal values. Overall results indicated that co-exposure induces a lower level of oxidative stress and AA ameliorates Pb- and/or CPM-induced oxidative damage in rat erythrocytes.     

Comparative studies of liver and brain glycogen content of male and female Clarias batrachus (L.) after exposure of different doses of arsenic

Different doses of arsenic (As) were used to investigate comparative toxicity on the liver and brain glycogen content on male and female Indian catfish Clarias batrachus (L.). As-induced effects were associated with gender, dose (5, 10, or 15?mg?L^?1), and varying time periods (48, 96, or 144?h). It was noted that As produced dose- and time-dependent liver glycogenolysis and late brain glycogenolysis. Liver glycogenolysis was significantly increased after 48?h at all three As doses. At the highest dose 15?mg?L^?1, liver glycogen were markedly diminished at in both male and female fish, but in females more reduction was observed than in males. However, with brain glycogen, the significant decrease was noted at 144?h with all three dose levels in both genders, with male being more susceptible. Thus, this study indicates that As produces glycogenolysis. The reduction in the liver glycogen content was more pronounced in female than in the male fish, whereas brain glycogen content decrease was more prominent in males.     

Sub-lethal toxic effects of deltamethrin on blood biochemical parameters of Japanese quail,Coturnix japonica

Feeding deltamethrin-contaminated grains to domestic poultry, such as quails may result in toxic effects in these birds. This study was done to investigate the effects of recommended doses of deltamethrin, sometimes used in grain storage silos, on Japanese quail (Coturnix japonica). Quails were fed grains contaminated with 0.25 and 0.50 mg deltamethrin per kg diet for 21 days and the effects on survival and blood biochemical parameters were studied. Plasma uric acid, creatinine levels, and creatinine phosphokinase activity in the blood were increased. Aspartate aminotransferase and lactate dehydrogenase activities and glucose levels significantly increased in birds treated with the high dose of deltamethrin. Alanine aminotransferase activity and albumin or cholesterol levels were not changed, and acetylcholinesterase and alkaline phosphatase activities, total protein and globulin in plasma were decreased. Administration of 0.25 mg/kg deltamethrin caused increased blood triglyceride levels, 0.50 mg/kg deltamethrin decreased triglyceride levels.     

Radical scavenging activity of Trianthema triquetra in male albino rats intoxicated with CCl4

Radical scavenging activity of ethanolic extract of Trianthema triquetra root was investigated against CCl4 in rats. The rats were treated with T. triquetra (100 mg, 200 mg/kg b.w.) for a period of 7 days. Antihepatotoxic effect was studied by assaying the activities of thiobarbituric acid (TBARS), reduced glutathione (GSH), glutathione peroxidase (GPx),catalase (CAT), super oxide dismutase (SOD) and vitamin C (Vit. C). Lipid peroxidation is evidenced by an increase in the value of TBARS and also a distinct diminution in the level of GSH, Vit. C at 200 mg/kg b.w. The activity of antioxidant enzymes, such as GPx, CAT SOD and Vit. E is significantly recovered towards an almost normal level in animals coadministrated with T. triquetra. The maximum protection against CCl4 induced hepatic injury was afforded by the dose of 200 mg/kg b.w. of Trianthema triquetra.     

Effect of mercuric chloride on circulating hormones in adult albino rats

The effect of mercuric chloride at two different doses, 0.5 mg/kg body weight (low dose), 1 mg/kg body weight (high dose), for 30 days, was seen on the circulating hormones in the mature male albino rats. Testosterone level was markedly decreased in the low dose (P < 0.01) and high dose (P < 0.001) treated animals. The level of luteinizing hormone (LH) was also reduced in the low dose (P < 0.01) as well as in the high dose (P < 0.001) treated animals. However, follicle stimulating hormone (FSH) and prolactin (PRL) levels were found to be decreased only in the high dose (P < 0. 05) treated animals and no change was observed in the low dose treated animals. The changes in the hormone levels caused by the mercuric chloride treatment suggest the dysfunction of pituitary-testicular axis.     

An experimental evaluation of transgenerational isotope labelling in a coral reef grouper

Transgenerational isotope labelling (TRAIL) using enriched stable isotopes provides a novel means of mass-marking marine fish larvae and estimating larval dispersal. The technique, therefore, provides a new way of addressing questions about demographic population connectivity and larval export from no-take marine protected areas. However, successful field applications must be preceded by larval rearing studies that validate the geochemical marking technique, determine appropriate concentrations and demonstrate that larvae are not adversely affected. Here, we test whether injection of enriched stable barium isotopes (¹³⁵Ba and ¹³⁷Ba) at two dose rates produces unequivocal marks on the otoliths of the coral reef grouper Epinephelus fuscoguttatus. We also assess potential negative effects on reproductive performance, egg size, condition and larval growth due to injection of adult female fish. The injection of barium isotopes at both 0.5 and 2.0 mg Ba/kg body weight into the body cavities of gravid female fish was 100% successful in the geochemical tagging of the otoliths of larvae from the first spawning after injection. The low-dose rate produced no negative effects on eggs or larvae. However, the higher dose rate of 2 mg Ba/kg produced small reductions in yolk sac area, oil globule area, standard length and head depth of pre-feeding larvae. Given the success of the 0.5 mg Ba/kg dose rate, it is clearly possible to produce a reliable mark and keep the concentration below any level that could affect larval growth or survival. Hence, enriched Ba isotope injections will provide an effective means of mass-marking grouper larvae.     

毒死蜱低剂量重复染毒致学习记忆功能障碍及CREB信号途径的抑制(Repeated Exposures to Low-Level Chlorpyrifos Result in Learning Memory Impairment and Inhibition of the CREB Signal System)

毒死蜱(CPF)是我国推荐使用的低毒有机磷农药之一,目前在全世界广泛应用.选择不引起动物出现全身系统毒性的CPF剂量(1、5、10mg·kg-1)对大鼠连续染毒4周,评价CPF对动物的学习记忆功能和CREB信号通路的影响.结果显示:CPF连续染毒后动物出现记忆能力的损伤,随着染毒剂量的增加,海马、皮质和纹状体CREB及ERKI/Ⅱ磷酸化蛋白表达逐渐减少,这表明ERK/CREB信号通路可能是参与毒死蜱低剂量重复暴露致学习记忆功能改变的重要途径.     

Subacute chlorpyrifos-induced alterations in serum lipids and some oxidative stress biomarkers in male Wistar rats: beneficial effect of acetyl-L-carnitine

The present study evaluated the beneficial effect of acetyl-L-carnitine (ALC) on subacute chlorpyrifos (CPF)-induced alterations in serum lipid profiles and some biomarkers of oxidative stress in Wistar rats. Twenty-eight adult male rats divided into four groups of seven animals each (group I–IV) were used: I (S/oil) received soya oil (2 ml kg^?1), II (ALC) received ALC (300 mg kg^?1); III (CPF) received CPF (8.5 mg kg^?1 ～ 1/10th LD₅₀); IV (ALC+CPF) was pretreated with ALC (300 mg kg^?1) and then exposed to CPF (8.5 mg kg^?1), 30 min later. The treatment was orally for 28 days duration. Sera obtained from blood samples were evaluated for the levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-c), malondialdehyde (MDA), and the activities of superoxide dismutase (SOD) and catalase (CAT). The levels of low density lipoprotein-cholesterol (LDL-c), very low density lipoprotein-cholesterol (VLDL-c), and atherogenic index (AI) were calculated. The result showed that elevated levels of TG, TC, LDL-c, VLDL-c, AI, and MDA, and the decreased levels of HDL-c, CAT, and SOD induced by CPF were modulated by ALC. It was concluded that ALC ameliorated the alterations in serum lipid and oxidative stress induced by CPF exposure in the rats, partly through its antioxidant properties.     

Effect of DDVP on the histology and AChE kinetics of heart muscles of Rattus norvegicus

The LD50 of DDVP (Dichloro, dimethyl vinyl phosphate) for Rattus norvegicus was 21.4 mg/kg. b.w. The two sub lethal doses 1 and 3 mg/kg showed many histopathological changes in the working heart muscles and also showed significant necrosis in this S-A node, A-V node and bunble of His of the cardiac conducting system. These sublethal doses of the OP pesticide caused a significant inhibition of AChE. The maximum inhibition was noticed at the highest dose. The enhanced inhibitory constant Km and ACh contents in the heart muscles with the increase of dose showed inhibition of enzyme. The constant Vmax showed competitive nature of inhibition. A significant inhibition of AChE (69%) indicated that DDVP is a strong inhibitor of enzyme in heart.     

Bromobenzene-induced hepatotoxicity in male rats: the protective effect of flaxseed

The metabolites of bromobenzene (BB) are hepatotoxic. The aim of this study was to determine the efficacy of different doses of flaxseed extract in alleviating BB-hepatotoxicity in male albino rats. Oxidative stress parameters, drug metabolizing enzymes, a pro-inflammatory marker, an apoptotic marker, and DNA fragmentation pattern were also assessed. Animals were divided into five groups treated by intragastric intubation as follows: control, BB-treated 460?mg?kg^?1?BW alone; three animal groups (III, IV, V) were treated concurrently with 460?mg?kg^?1 BB daily for 3 weeks and different doses of flaxseeds extract: 100, 200, or 300?mg?kg^?1?BW. Oral treatment of BB produced a significant decrease in activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase and glutathione levels, while activities of glutathione reductase and drug-metabolizing enzymes; glutathione-S-transferases and cytochrome P450 were enhanced. BB-treatment resulted in enhanced production of nitric oxide and activation of COX-2 and caspase-3. Pre-treatment with different doses of flaxseeds extract prior and during BB-treatment protected liver against BB-induced hepatotoxicity. The lower dose of flaxseed extract (100?mg?kg^?1) was most effective one.     

Validation of QuEChERS-based method for determination of flusilazole residues in grape by high-performance liquid chromatography with photodiode array detector

A high-performance liquid chromatography with photodiode array detector analytical method was developed to determine the residue levels of flusilazole in grape and investigate the dissipation pattern and safety. The results showed that the mean recoveries were in the range of 86%–90%. Limits of detection and quantification were 0.008 and 0.02 mg/kg, respectively. The residue levels of flusilazole were best described by first-order rate kinetics and with half-lives ranging from 4.2 days (recommended dose) to 4.6 days (double the recommended dose). In conclusion, flusilazole at the recommended or even at double the recommended doses does not pose any apparent hazards to consumers.     

Impact of chlorpyrifos on cerebrum and cerebellum maturity in suckling rats

The purpose of our study is to assess the effect of chlorpyrifos (CPF) on rat cerebral and cerebellar maturity during the suckling period. Female Wistar rats were given 0.2?g?L^?1 of CPF in drinking water, equivalent to 40?mg?kg^?1 of body weight?day^?1, from day zero until day ten after delivery. In treated pups, plasma butyrylcholinesterase (BuChE) activity was inhibited by 70%. Cerebrum and cerebellum acetyl-cholinesterase (AchE) activities were reduced by 71 and 75%, respectively. The results suggest that CPF was distributed in pup tissues through the milk of lactating mothers, resulting in inhibition of AchE activities. At age 10 days, the CPF-treated pups showed a 28% decrease in body weight, a 23 and 41% decrease in plasma free T₃ and T₄ levels and reduction in cerebral and cerebellar protein content by 36 and 38%, respectively. Consistent histological changes were found in the cerebellum of CPF treated pups, with the external granular layer being markedly developed, the Purkinje cell bodies being poorly differentiated and abnormally distributed into the internal granular layer.     

Chlorpyrifos induces oxidative stress in rats

This study was carried out in male Wistar rats to determine the potential effects of chlorpyrifos (CHP) on oxidative stress, as was reported for organophosphorus (OP) pesticides. Following an acute, daily 3- or 14-day exposure with CHP at doses of 2.5, 5, or 25 mg kg^?1 data showed significant increases in malondialdehyde levels at both exposure durations and at all doses, except for 2.5 mg kg^?1, in hepatic and aorta, kidney, and plasma samples. The nitrites (NO) showed elevation at 25 mg kg^?1 in aorta, at 3- and 14-day exposure, in hepatic tissue with all doses at 3-day exposure, but not at 14-day with a 5 mg kg^?1 dose. In plasma, increases occurred only at 25 mg kg^?1 at both exposure times, and in kidney at all doses and both exposure durations. Superoxide dismutase (SOD) enzyme activity in the aorta sample was statistically significant at all doses at 3 days and at 14 days, except at 2.5 mg kg^?1; and in hepatic tissue only at 25 mg kg^?1 dose at both durations. In plasma SOD activity was elevated at all doses at 3 days, but at 14 days only at 25 mg kg^?1. Data suggests that oxidative stress may be involved in the effects of CHP on rats.     

Effect of titanium dioxide nanoparticles on the expression of apoptotic markers in mouse blastocysts

Oocyte maturation, embryo development and expression of apoptotic-specific genes were evaluated in blastocysts of mice treated with titanium dioxide nanoparticles. Female mice received 0, 50 or 100?mg/kg/day titanium dioxide intraperitoneally for five consecutive days. After the last injection, pregnant mare serum gonadotropin and, 48?h later, human chorionic gonadotropin were administered intraperitoneally for induction of ovulation. After 14?h, mice were sacrificed and oocytes were collected. The number of mature oocytes was evaluated and then fertilization was carried out in vitro and the numbers of fertilized and cleaved oocytes and of blastocysts and the expression of Bax, caspase 3, and Bcl-xL genes in blastocysts were evaluated. The number of mature, fertilized and cleaved oocytes and of blastocyst embryos in the experimental groups were not different from control. The expression of Bax and caspase 3 genes was significantly elevated in the experimental groups compared to control, while expression of the Bcl-xL gene was significantly lower in the high dose group. Uptake of titanium dioxide nanoparticles at daily doses of 50?mg/kg and more may affect embryo development by alteration of pro-apoptotic and anti-apoptotic gene expression.