Subacute Intoxication Research Articles

Protective Role of Bergamot Polyphenolic Fraction (BPF) against Deltamethrin Toxicity in Honeybees (Apis mellifera).

Pesticide-induced poisoning phenomena are a serious problem for beekeeping and can cause large losses of honeybee populations due to acute and sub-acute poisoning. The reduced responsiveness of honeybees to the damage caused by pesticides used in agriculture can be traced back to a general qualitative and quantitative impoverishment of the nectar resources of terrestrial ecosystems. Malnutrition is associated with a decline in the functionality of the immune system and the systems that are delegated to the detoxification of the organism. This research aimed to verify whether bergamot polyphenolic extract (BPF) could have protective effects against poisoning by the pyrethroid pesticide deltamethrin. The studies were conducted with caged honeybees under controlled conditions. Sub-lethal doses of pesticides and related treatments for BPF were administered. At a dose of 21.6 mg/L, deltamethrin caused mortality in all treated subjects (20 caged honeybees) after one day of administration. The groups where BPF (1 mg/kg) was added to the toxic solution recorded the survival of honeybees by up to three days. Comparing the honeybees of the groups in which the BPF-deltamethrin association was added to the normal diet (sugar solution) with those in which deltamethrin alone was added to the normal diet, the BPF group had a statistically significant reduction in the honeybee mortality rate (p ≤ 0.05) and a greater consumption of food. Therefore, it can be argued that the inclusion of BPF and its constituent antioxidants in the honeybee diet reduces toxicity and oxidative stress caused by oral intake of deltamethrin. Furthermore, it can be argued that BPF administration could compensate for metabolic energy deficits often induced by the effects of malnutrition caused by environmental degradation and standard beekeeping practices.

Organophospate-Induced Pathology: Mechanisms of Development, Principles of Therapy and Features of Experimental Studies

Organophosphates (OP) are one of the most common neurotoxic xenobiotics. In acute OP poisoning, as a result of suppression of synaptic acetylcholinesterase (AChE) activity, a cholinergic syndrome develops, which can transform into status epilepticus. Within a few days after acute poisoning, the so-called an intermediate syndrome can develop, which is associated with prolonged inhibition of AChE, desensitization of nicotinic receptors, and functional degradation of synapses and muscle fibers. In 10–20 days after a single acute or repeated subacute poisoning, OP-induced delayed polyneuropathy (OPIDN) can develop – a neurodegenerative disease, the signs of which are ataxia, loss of function of the distal sensory and motor axons of peripheral nerves. The occurrence of a neuropsychiatric disorder (NPD) caused by chronic exposure to relatively low-toxicity organophosphorus compounds is usually not associated with acute poisoning; symptoms include cognitive impairment, chronic fatigue, and extrapyramidal symptoms. The list of possible diseases or pathological conditions (syndromes) that develop as a result of acute, subacute or chronic effects of OP on the human body has expanded in recent years due a number of known neurodegenerative diseases (Alzheimer’s, Parkinson’s, multiple sclerosis, etc.). The aging of the body in general and the aging of the brain in particular are considered in the review from the point of view of the consequences of OP poisoning, which can serve as a nonspecific trigger of aging and related neurodegenerative diseases. Gulf syndrome is not a consequence of OP intoxication, but is also of interest and is considered in the context of OP-induced pathology, since its etiology and pathogenesis are associated with the exposure to cholinesterase inhibitors. The review presents data indicating the important role of the vascular endothelium in the development of OP-induced pathology; The first suggestions were made by clinicians in the late 1980s, and the first experimental data were obtained in the early 2000s. The principles of therapy for acute poisoning are outlined, taking into account experimental data from recent years. Some methods for studying OP in experiments in vitro, ex vivo and in vivo with laboratory animals, including the use of carboxylesterase inhibitors, are presented. The most important part of in vivo investigations has been and remains the search for new biomarkers to assess the effectiveness of adjuvant and regenerative therapies.

Effect of dihydroquercetin on the toxic properties of nickel nanoparticles

Dihydroquercetin (3,5,7,3',4'-pentahydroxy-flavanone) is known for its powerful antioxidant, organ-protective, and antiinflammatory activities that can be applied to heavy-metal intoxication. The present research objective was to evaluate the possible protective potential of dietary dihydroquercetin in a rat model of subacute (92 days) intoxication with nickel nanoparticles.
 The experiment involved five groups of twelve male Wistar rats in each. Group 1 served as control. Other groups received nickel nanoparticles as part of their diet. Groups 2 and 4 received nickel nanoparticles with an average diameter of 53.7 nm (NiNP1), while groups 3 and 5 were fed with nanoparticles with an average diameter of 70.9 nm (NiNP2). The dose was calculated as 10 mg/kg b.w. Groups 4 and 5 also received 23 mg/kg b.w. of water-soluble stabilized dihydroquercetin with drinking water. 
 After the dihydroquercetin treatment, the group that consumed 53.7 nm nickel nanoparticles demonstrated lower blood serum glucose, triglycerides, low-density lipoprotein cholesterol, and creatinine. Dihydroquercetin prevented the increase in total protein and albumin fraction associated with nickel nanoparticles intake. The experimental rats also demonstrated lower levels of pro-inflammatory cytokines IL-1β, IL-4, IL-6, and IL-17A, as well as a lower relative spleen weight after the treatment. In the group exposed to 53.7 nm nickel nanoparticles, the dihydroquercetin treatment increased the ratio of cytokines IL-10/IL-17A and decreased the level of circulating FABP2 protein, which is a biomarker of increased intestinal barrier permeability. In the group that received 70.9 nm nickel nanoparticles, the dihydroquercetin treatment inhibited the expression of the fibrogenic Timp3 gene in the liver. In the group that received 53.7 nm nickel nanoparticles, dihydroquercetin partially improved the violated morphology indexes in liver and kidney tissue. However, dihydroquercetin restored neither the content of reduced glutathione in the liver nor the indicators of selenium safety, which were suppressed under the effect of nickel nanoparticles. Moreover, the treatment failed to restore the low locomotor activity in the elevated plus maze test.
 Dihydroquercetin treatment showed some signs of detoxication and anti-inflammation in rats subjected to nickel nanoparticles. However, additional preclinical studies are necessary to substantiate its prophylactic potential in cases of exposure to nanoparticles of nickel and other heavy metals.

Quercetin Protected from Aluminum Phosphide-induced Acute and Subacute Cardio- and Hepatotoxicity in Rats.

Aluminum phosphide (ALP) intoxication either accidentally or intentionally, is one of the major health concerns in developing countries. Its poisoning causes severe damage to organs including the heart and liver. This study aimed to investigate the hepato- and cardioprotective effects of quercetin (QCN) on the acute/subacute toxicity of ALP in rodent models. Acute (single dose, 12.5 mg/kg, orally) and subacute (2 mg/kg, orally and 7 days) intoxication of ALP were induced in rats and the protective effects of QCN on altered hepatic/cardiac functional enzyme concentrations, myeloperoxidase activity, oxidative stress biomarkers, and histopathological changes were studied at three doses of 10, 50 and 100 mg/kg BW. To record any heart abnormality, an electrocardiogram (ECG) was recorded 3 h after the last treatment. Quercetin reduced the ALP-increased hepatic and cardiac functional enzyme concentrations and myeloperoxidase activity. Moreover, QCN improved remarkably the ALP-induced ECG abnormalities (T inversion, bigeminy in R waves) and arrhythmias. QCN attenuated significantly (p < 0.05) the ALP-induced oxidative/ nitrosative stress and histopathological injuries in the liver and heart. Our results suggest that QCN is able to protect the ALP-induced cardiac and hepatic injuries in both acute and subacute models and its effects attribute to its antioxidant and anti-inflammatory properties.

The who and how of attentional bias in cannabis users: associations with use severity, craving and interference control.

Cognitive and motivational processes are thought to underlie cannabis use disorder (CUD), but research assessing how cognitive processes [e.g. interference control (IC)] interact with implicit [e.g. attentional bias (AB)] and explicit motivation (i.e. craving) is lacking. We assessed the presence of AB in cannabis users with varying use severity and tested models of moderation, mediation and moderated mediation to assess how AB, craving and IC interact in their association with measures of cannabis use. A cross-sectional study design was used. Eight studies performed by our laboratory in the Netherlands including never-sporadic, occasional (≤ 1/month) and regular cannabis users (≥ 2/week), and individuals in treatment for CUD were combined (n = 560; 71% male). Studies included a classic Stroop task (IC), a cannabis Stroop task (AB) and measures of session-induced and average session craving. Both heaviness of cannabis use (grams/week) and severity of use related problems were included. Only those in treatment for CUD showed an AB to cannabis (P = 0.019) and group differences were only observed when comparing CUD with never-sporadic users (P = 0.007). In occasional and regular users, IC was negatively associated with heaviness (β = 0.015, P < 0.001), but not severity of use. Average session craving (exploratory), but not session-induced craving (confirmatory), mediated this association between AB and heaviness (β = 0.050, P = 0.011) as well as severity of use (β = 0.083, P = 0.009); higher AB was associated with heavier use and more severe problems through increased craving. Attentional bias only appears to be present in cannabis users with the most severe problems and craving appears to mediate the association between attentional bias and both heaviness and severity of use in occasional and regular users. The association of interference control with heaviness but not severity of use may point to subacute intoxication effects of cannabis use on interference control.

Effect of subacute poisoning with lambdacyhalothrin on vascular endothelial growth factor 2 receptor in mice kidneys

BackgroundPyrethroids are used for insect control. They act on voltage-gated sodium channels in neurons. Lambdacyhalothrin (LCH) is a type II pyrethroid producing choreoatetosis and salivation in rodents. Vascular endothelial growth factor (VEGF) expression in the kidney is high in the glomerular podocytes and kidney tubules. VEGF receptor 2 (VEFGR2) is the main mediator in angiogenesis and it regulates blood vessel permeability. Lack of VEGF in podocytes impairs filtration. The nuclear factor κB (NFκB) is widely known as an important mediator of inflammation.The aim of the study was to check if subacute oral intoxication with 0.1LD50 of LCH affects kidney size, function and VEGFR2 and NFκB in mice kidneys.MethodsA total of 32 Albino Swiss mice was used: females controls, males controls, females receiving 2 mg/kg LCH, males receiving 2 mg/kg LCH orally for 7 days. On day 8 animals were sacrificed, blood and kidneys were obtained. Kidney mass was determined, creatinine concentration was measured in blood sera, VEGFR2 and NFκB in kidney homogenate supernatant with ELISA kit.ResultsThere was no statistically significant differences in kidney mass, creatinine concentration in blood sera nor NFκB but mean VEGFR2 concentration in the kidneys of females exposed to LCH was 128.01 ng/ml and showed statistically significant difference in comparison with control females. There was no statistically significant difference between VEGFR2 concentration in the kidneys of males exposed to LCH and control males.ConclusionThe VEGFR2 increases in the course of LCH intoxication in females probably due to the protective effect of oestrogens.

The Effect of Subacute Poisoning with Deltamethrin on the Levels of Interleukin 1ß and Tumour Necrosis Factor Α in the Livers and Kidneys of Mice

Abstract Deltamethrin is a type II pyrethroid. Deltamethrin’s action is characterised by nephrotoxicity, hepatotoxicity and immunotoxicity. The aim of the study was to evaluate the effect of poisoning with deltamethrin on the levels of interleukin1ß and TNFα in the livers and kidneys of mice. A total of 24 female mice were divided into 3 groups of 8: - controls, - receiving deltamethrin i.p. at the dose of 41.5 mg/kg for 28 days - receiving deltamethrin i.p. at the dose of 8.3 mg/kg for 28 days. On day 29 the animals were euthanised, livers and kidneys were obtained, homogenised and centrifuged. The supernatant was used for measuring IL-1ß and TNFα concentration with ELISA tests. The results were analysed with Statsoft Statistica. The interleukin 1ß concentrations were significantly higher in the kidneys (18.30±16.85) of mice exposed to the higher dose of deltamethrin than in the controls (8.15±4.66) (p&lt;0.05). In the livers of mice receiving 41.5mg/kg deltamethrin it was 203±71.63 vs 46.77±34.79 (p&lt;0.05). In the livers of animals receiving the lower dose it was higher than in the control group (96.51±24.73) (p&lt;0.05). The TNF α was elevated in the kidneys of mice exposed to the higher dose of deltamethrin (6.56±3.26 vs 2.89±1.57)(p&lt;0.05). Conclusion: Deltamethrin produces a significant increase of interleukin 1ß in the livers and kidneys of mice and so the cytokine seems to be a good marker of hepatotoxicity and nephrotoxicity in the course of subacute poisoning.

Influence of Pancreo-Plant on the histological parameters of the liver in conditions of acute toxic hepatitis

Toxic liver damage is the most problematic for pharmacotherapy and, accordingly, the normalization of the patient’s condition. Most often, hepatotoxins include alcohol, drugs, household and industrial toxins, the effect of which on the liver leads to the development of hepatocyte necrosis. The peculiarity of drug toxic hepatitis is a wide range of clinical manifestations, the absence of unambiguous diagnostic methods, frequent poor prognosis, which makes toxic hepatitis one of the most difficult problems in clinical practice. A promising drug for the treatment of toxic liver damage is a multicomponent herbal remedy, which is currently produced by a domestic manufacturer in the form of a dietary supplement. The aim of the work is to study the effect of the herbal remedy Pancreo-Plant on the histological structure of the liver of rats, under conditions of subacute ethanol-tetrachloromethane intoxication. Materials and methods. A model of poisoning was formed and liver samples from nonlinear white rats were examined. The slides were examined under the light microscope Granum, photographing of microscopic images was carried out with Granum DCM 310 digital video camera. The photographs were processed on a computer using the Toup View program. Results. Micropreparations obtained from liver samples of rats under the condition of subacute ethanol-tetrachloromethane intoxication, were investigated. It has been proven that Pancreo-Plant helps to reduce necrotic manifestations, hydropic degeneration of hepatocytes, manifestations of steatosis, and signs of inflammation; it also stimulates carbohydrate metabolism in hepatocytes and improves regenerative manifestations. Conclusions. It was found that the investigated agent based on medicinal plant materials, when using the model of subacute ethanol-tetrachloromethane intoxication, exhibits a significant hepatoprotective effect. It normalizes the histological structure of hepatocytes, restores the processes of glycogen accumulation, and prevents the development of fatty degeneration of the liver.

Reactive astrocytes induced by 2-chloroethanol modulate microglia polarization through IL-1β, TNF-α, and iNOS upregulation

The synthetic organic chemical, 1,2-dichloroethane (1,2-DCE), can cause brain edemas under subacute poisoning. Our previous studies indicated that neuroinflammation could be induced due to astrocytes and microglia activation during brain edemas in 1,2-DCE-intoxicated mice. However, the crosstalk between these two glial cells in 1,2-DCE-induced neuroinflammation remained unclear. In this study, primary cultured rat astrocytes and microglia, as well as an immortalized microglia cell line were employed to study the effects of 2-chloroethanol (2-CE, a 1,2-DCE intermediate metabolite in vivo) treated astrocytes on microglia polarization. Our current results revealed that 2-CE treated rat astrocytes were activated through p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor-κB (NF-κB), and activator protein-1 (AP-1) signaling pathways. Theses pathways were triggered by reactive oxygen species (ROS) produced during 2-CE metabolism. Also, astrocytes were more sensitive to 2-CE effects than microglia. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) expressions were upregulated in 2-CE-induced reactive astrocytes, enhancing IL-1β, TNF-α, and nitric oxide (NO) excretions, which stimulated microglia polarization. Therefore, the neuroinflammation induced by 1,2-DCE in mice's brains is probably triggered by reactive astrocytes.

Hematological parameters in rats poisoned with cadmium nitrate and in biocorrection with the infusion of Beta vulgaris seeds

Nowadays, using plant extracts and infusions as protectors against the impact of heavy metals, the molecular mechanisms, protective and adaptive reactions of plants are studied. The purpose of this article was to study the protective properties of beetroot seeds infusion in acute and sub-acute poisoning of rats with cadmium nitrate. For this experiment, we used 50 male rats. The animals were exposed to Cd nitrate, with an initial weight of 180 ± 30 g. The first groups of rats were injected with cadmium nitrate at a dose of 0.1 g/L intraperitoneally, the second groups received a 0.01 % solution of cadmium nitrate, 1 mL, 5 days a week, orally for 10 and 24 days. General blood tests and biochemical parameters in rats were investigated. By biochemical parameters, we determined liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, glucose, urea, creatinine, and total protein. The mean ± SEM values were calculated for each group to determine the significance of the intergroup difference. Each parameter was analyzed separately using the one-way analysis of variance (ANOVA) test. To determine the difference between groups, Student’s «t»-test was used. Studies showed the presence of variations in the parameters of leukocytes, erythrocytes and platelets depending on the period of days of poisoning and biocorrection. There were small changes in the content of urea, creatinine, and protein, which were not reliably confirmed. As a result, our research allowed asserting that the use of Beta vulgaris infusion in acute and subacute experiments with poisoning of animals with cadmium nitrate had a positive hepatoprotective effect.

Influence of antitox and Vitamin E-selenium on meat quality and safety in rabbits after 1,1-experimental dimethylhydrazine toxicosis.

Aim:This study investigated the effects of antitox and Vitamin E-selenium on meat quality and safety in rabbits after experimental 1,1-dimethylhydrazine (1,1-DMH) toxicosis.Materials and Methods:Experimental groups of rabbits weighing 1.5-2.5 kg each were kept in a vivarium under same controlled conditions (temperature 16-21°C, humidity 60-80%, 12/12 h light/dark cycle, noise level <85 dB) with free access to standard food containing 22.0% protein, 4.5% fat, and 4% fiber. The effect of a detoxifying mixture of antitox and Vitamin E-selenium on safety indicators (residual amount of 1,1-DMH) and quality indicators pre- and post-detoxification of the rabbits from 1,1-DMH was determined.Results:After detoxification, the residual 1,1-DMH level decreased in all organs and tissues to <0.1 mg/kg. The nutritional value of meat increased by improving organoleptic, physical, and chemical parameters and the amino acid composition of protein.Conclusion:The antitox+Vitamin E-selenium detoxifying mixture significantly decreases the residual 1,1-DMH level in organs and tissues of animals and increases the nutritional value of rabbit meat in subacute poisoning. The detoxifying mixture can also be used on animals grazing in territories adjacent to Proton-M launch sites for preventive and therapeutic purposes.

Effect of Subacute Intoxication with Nitrite on AMP-Deaminase Activity in Skeletal Muscles of Common Carp (Cyprinus carpio)

This study was aimed to evaluate the effects of intoxication of common carp with nitrite on some properties of Adenosine 5´-monophosphate (AMP) deaminase in the skeletal muscle. LC50 value was determined to be 512 mg/L. After estimating the LC50, fish were exposed to 153 mg/L (30% LC50) and sampling was done at 0, 24, 48, 72, and 96 h after exposure. Cytosolic AMP deaminase was purified from the skeletal muscle of the control and experimental groups. AMP-deaminase showed Hill kinetics with an S0.5 value for AMP of 2.52±0.031 and 1.45±0.07 mM, a Hill coefficient (nH) of 1.35±0.051 and 1.79±0.60, and a maximal velocity (Vmax) of 133.39±28 and 98.9±38 IU/mg protein for the control and experimental groups, respectively after 96 h. The optimum pH was reduced during nitrite intoxication. The maximal activation of the enzyme was at 45ºC. Also, activation energy declined in the experimental groups. Fenton reaction showed that the enzyme was tolerant to free radicals. According to the results, AMP deaminase activity in the common carp’s muscles increased following nitrite intoxication. Also, acidic condition increased AMP deaminase activity that could be an adaptive response to hypoxic condition caused by nitrite intoxication.

Neuroinflammatory Reactions in the Brain of 1,2-DCE-Intoxicated Mice during Brain Edema.

We previously reported that expression of matrix metalloproteinase-9 (MMP-9) mRNA and protein was upregulated during 1,2-dichloroethane (1,2-DCE) induced brain edema in mice. We also found that the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway resulted in MMP-9 overexpression and nuclear factor-κB (NF-κB) activation in mice treated with 1,2-DCE. In this study, we further hypothesized that inflammatory reactions mediated by the p38 MAPK/ NF-κB signaling pathway might be involved in MMP-9 overexpression, blood–brain barrier (BBB) disruption and edema formation in the brain of 1,2-DCE-intoxicated mice. Our results revealed that subacute poisoning by 1,2-DCE upregulates protein levels of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), interleukin-1β (IL-1β), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and p-p65 in mouse brains. Pretreatment with an inhibitor against p38 MAPK attenuates these changes. Moreover, pretreatment with an inhibitor against NF-κB attenuates alterations in brain water content, pathological indications notable in brain edema, as well as mRNA and protein expression on levels of MMP-9, VCAM-1, ICAM-1, iNOS, and IL-1β, tight junction proteins (TJs), GFAP and Iba-1 in the brain of 1,2-DCE-intoxicated mice. Furthermore, pretreatment with an inhibitor against MMP-9 obstructs the decrease of TJs in the brain of 1,2-DCE-intoxicated mice. Lastly, pretreatment with an antagonist against the IL-1β receptor also attenuates changes in protein levels of p-p38 MAPK, p-p65, p-IκB, VCAM -1, ICAM-1, IL-1β, and Iba-1 in the brain of 1,2-DCE-intoxicated-mice. Taken together, findings from the current study indicate that the p38 MAPK/ NF-κB signaling pathway might be involved in the activation of glial cells, and the overproduction of proinflammatory factors, which might induce inflammatory reactions in the brain of 1,2-DCE-intoxicated mice that leads to brain edema.

STRUCTURAL-FUNCTIONAL REORGANIZATION OF SKIN AND ITS DERIVATIVES UNDER EXPERIMENTAL SUBACUTE OF INTOXICATION BY HEAVY METALS

There was executed an experimental study of the effect of salts of heavy metals (nickel, chromium, lead and zinc) entering the body by peroral route, on the morphology of the skin and its derivatives (hair follicles and sebaceous glands). The experiment was performed on C57BL / 6 mice with the use of the induction of hair follicle cycle by depilation. Under the subacute intoxication with salts of nickel, chromium and lead, there were revealed such signs of a dystrophic anagen as ectopia of granules of melanin in the dermal papilla and perifollicular tissue, enlarged channels of the hair. The duration of the anagen stage if compared with the control did not change. Under the intoxication with salts of nickel and lead there was revealed infiltration by mononuclear dermis and hypodermis. Lead acetate gave rise in the capillary congestion of the dermis, followed by diapedesis of erythrocytes and infiltration of the dermis by siderophages. In the course of the immunohistochemical study of the proliferative activity of keratinocytes of the skin integument derivatives with the use of antibodies to Ki-67, there was revealed a significant increase of proliferative activity of keratinocytes in comparison with the control under the use of a solution of zinc sulphate and sodium dichromate and its decrease with the use of lead acetate solution.

Sex differences in subacute manganese intoxication: Oxidative parameters and metal deposition in peripheral organs of adult Wistar rats

IntroductionManganese (Mn) is an essential element required for several biological systems. However, it is toxic in excessive accumulation. The toxic effects following Mn overexposure is well known in the CNS but other studies evaluating other target tissues remain scarce. ObjectiveThis study aimed to investigate sex-related differences in oxidative stress, metabolic parameters and Mn deposition in peripheral organs of Wistar rats exposed to subacute model of intoxication. MethodsMale and female adult Wistar rats received 6 or 15 mg/kg of MnCl2, intraperitoneally, 5 days a week, for 4 consecutive weeks to mimic subacute intoxication. Control group received sterile saline 0,9% following the same protocol. After this period, the metal accumulation, oxidative stress, mitochondrial activity and histological parameters in cardiac muscle, kidney, lungs and liver were analysed. ResultsIncreased Mn concentrations were found in all organs, especially kidneys. The cardiac muscle analysis revealed increased lipid peroxidation and decreasing of GSH levels in both doses of Mn in male and female rats. The increase of lipid peroxidation in liver was more evident in the male group, and there was a significant decrease of antioxidant capacity in males’ kidney. Nevertheless, there was an increase of mitochondrial complex I activity in kidney of females and increase of mitochondrial complex II activity in male group. Histological analysis revealed morphological changes in hepatic and pulmonary tissue. ConclusionTaken together, our results showed that subacute Mn exposure lead to significant metabolic, biochemical alterations especially in kidney and liver. Nevertheless, despite Mn deposition was virtually the same in the peripheral organs of male and female rats, it promotes different toxic effects between sexes.

Effect of bee pollen extract on lead-induced toxicity in rat testis

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Stress induced by beta-cyfluthrin, a type-2 pyrethroid, on brain biochemistry of Albino rat (Rattus norvegicus)

Beta-Cyfluthrin is one of the most widely used type-II pyrethroid in agriculture. Toxic effects of beta-cyfluthrin are due to the presence of cyano moiety in its chemical structure. This study was designed the effect of betacyfluthrin at different doses on brain tissue, the most important vital organ in animal body and in which dose level beta-cyfluthrin shows its effects. Animal were initially divided into control and beta-cyfluthrin given groups. There were five animals in the control group and twenty five animals in beta-cyfluthrin administered group. The latter was divided into five equal subgroups: 35.48, and 5.06, 2.53, 1.68, 1.27mg/kg body weight of beta-cyfluthrin administered groups, acute (1 day) and sub-acute (7, 14, 21 and 28 days) by gavage respectively. Control group was given only water. The effect of these treatments were studied on activities of four potential biomarkers were assayed in the brain of albino rat along with neurosomatic index viz. Body weight, brain weight and brain weight body weight ratio and neurobehavioural changes. Beta-cyfluthrin treatment resulted in a significant decrease in brain acetyl-cholinesterase. Acetylcholinesterase which found to be decreased (inhibition range 53 to 18%) in albino rats after acute and sub-acute treatment (vide-supra). Further glutathione-s-transferase (GST) was also found to be decreased in brain of albino rats (inhibition range 47 to29%) after beta-cyfluthrin administration. Again brain adenosine triphosphtase (total ATPase) activity was seen to decrease in albino rats (inhibition range 36 to19%) along with succinic dehydrogenase (SDH) was also seen decreased in brain of albino rats (inhibition range 31 to 9%)) after acute and sub-acute beta-cyfluthrin intoxication. Further hypnoatremia (inhibition range 31 to 20%) along with hypokalemia (inhibition range 19 to 14%) has also been observed after acute and sub-acute intoxication of beta-cyfluthrin. Apart from AChE, which is a specific marker of pyrethroid neurotoxicity, the levels of brain GST, ATPase, SDH along with Na and K may serve as important determinants of beta-cyfluthrin induced neuronal dysfunctioning along with neurobehavioural alterations; outcomes of fluctuated brain biochemistry because clinical signs of toxicity were observed in animals which received different doses of beta-cyfluthrin after 7 th , and 14 th days of sub-acute treatment. Animals showed overt cholinergic signs which included salivation, excitability, ataxia, muscle twisting, followed by general tremors and lethargyness. The treated groups did not reveal any mortality. Exposure of animals to beta-cyfluthrin caused extensive changes in neurosomatic, neurochemical and neurobehavioural parameters. So, oral administration of beta-cyfluthrin leads to negative response on animal health.

Involvement of CYP2E1 in the Course of Brain Edema Induced by Subacute Poisoning With 1,2-Dichloroethane in Mice.

This study was designed to explore the role of cytochrome P4502E1 (CYP2E1) expression in the course of brain edema induced by subacute poisoning with 1,2-dichloroethane (1,2-DCE). Mice were randomly divided into five groups: the control group, the 1,2-DCE poisoned group, and the low-, medium- and high-dose diallyl sulfide (DAS) intervention groups. The present study found that CYP2E1 expression levels in the brains of the 1,2-DCE-poisoned group were upregulated transcriptionally; in contrast, the levels were suppressed by DAS pretreatment in the intervention groups. In addition, the expression levels of both Nrf2 and HO-1 were also upregulated transcriptionally in the brains of the 1,2-DCE-poisoned group, while they were suppressed dose-dependently in the intervention groups. Moreover, compared with the control group, MDA levels and water contents in the brains of the 1,2-DCE-poisoned group increased, whereas NPSH levels and tight junction (TJ) protein levels decreased significantly. Conversely, compared with the 1,2-DCE- poisoned group, MDA levels and water contents in the brains of the intervention groups decreased, and NPSH levels and TJ protein levels increased significantly. Furthermore, pathological changes of brain edema observed in the 1,2-DCE-poisoned group were markedly improved in the intervention groups. Collectively, our results suggested that CYP2E1 expression could be transcriptionally upregulated in 1,2-DCE-poisoned mice, which might enhance 1,2-DCE metabolism in vivo, and induce oxidative damage and TJ disruption in the brain, ultimately leading to brain edema.

Subacute intoxication with sodium nitrate induces hematological and biochemical alterations and liver injury in male Wistar rats

Nitrate pollution has emerged as a problem of great importance because in recent years, the levels of nitrate in soil and groundwater have increased, mainly through anthropogenic activities, such as the use of fertilizers in agriculture, domestic wastewater and septic tanks, industrial waste and deforestation. In animals, nitrate reduction to nitrite (NO2) and nitric oxide (NO) promote the formation of methemoglobin in the blood and the generation of highly reactive intermediates that induce oxidative stress in target organs. Exposition to nitrates has been associated with methemoglobinemia, reproductive toxicity, metabolic and endocrine alterations and cancer. This study analyzed acute intoxication with sodium nitrate (NaNO3) in male Wistar rats, aged 12–16 weeks. Four groups with n = 10 rats each were formed: group 1 was the control, and group 2, group 3 and group 4 were treated for 10 days with intragastric doses of 19, 66 and 150 mg/kg/d NaNO3, respectively. Hematological, metabolic and histological biomarkers in the liver were analyzed. The results showed high percentages of methemoglobin, an increase in NO2 in the plasma and an accumulation in the liver. Moreover, there were high counts of white blood cells and platelets in all treated groups. Additionally, there was an increase in the spleen weight in group 4. High levels of glucose, triglycerides, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were observed and were significantly increased in groups 3 and 4. For oxidative stress biomarkers, there were increases in Thiobarbituric Acid Reactive Substances (TBARS), total GSH and SOD activity, mainly in group 4. Changes in mitochondrial activity were not significant. Histopathological analyses of the liver showed inflammation, infiltration of mononuclear cells, steatosis, ischemia and necrosis, and these findings were more evident at high doses of NaNO3 in which high of S-nitrosylation were found. In conclusion, NaNO3 was reduced to NO2, thereby inducing methemoglobinemia, whereas other reactive species generated oxidative stress, causing hematological and metabolic alterations and injury to the liver.

Association of NF-κB and AP-1 with MMP-9 Overexpression in 2-Chloroethanol Exposed Rat Astrocytes.

Subacute poisoning of 1,2-dichloroethane (1,2-DCE) has become a serious occupational problem in China, and brain edema is its main pathological consequence, but little is known about the underlying mechanisms. As the metabolite of 1,2-DCE, 2-chloroethanol (2-CE) is more reactive, and might play an important role in the toxic effects of 1,2-DCE. In our previous studies, we found that matrix metalloproteinases-9 (MMP-9) expression was enhanced in mouse brains upon treatment with 1,2-DCE, and in rat astrocytes exposed to 2-CE. In the present study, we analyzed the association of nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) with MMP-9 overexpression in astrocytes treated with 2-CE. MMP-9, p65, c-Jun, and c-Fos were significantly upregulated by 2-CE treatment, which also enhanced phosphorylation of c-Jun, c-Fos and inhibitor of κBα (IκBα), and nuclear translocation of p65. Furthermore, inhibition of IκBα phosphorylation and AP-1 activity with the specific inhibitors could attenuate MMP-9 overexpression in the cells. On the other hand, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway suppressed the activation of both NF-κB and AP-1 in 2-CE-treated astrocytes. In conclusion, MMP-9 overexpression induced by 2-CE in astrocytes could be mediated at least in part through the p38 signaling pathway via activation of both NF-κB and AP-1. This study might provide novel clues for clarifying the mechanisms underlying 1,2-DCE associated cerebral edema.