Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. This study aimed to investigate the effect of curcumin on neurobehavioral and neuropathological alterations induced by acetamiprid on male rats. Three groups of ten male Wistar rats each were used for the study: the first was a control group (CTR) that did not consume acetamiprid (ACE); the second was an experimental group (ACE) that consumed 40 mg/kg body weight/day of acetamiprid; and the third group (CUR) received curcumin (100 mg/kg) and acetamiprid (40 mg/kg) in combination. Neurobehavioral evaluations including inclined plane performance and forepaw grip time were studied. Treatment with CUR significantly prevented ACE-treated rats from impairments in the performance of neurobehavioral tests, indicating the presence of deficits on sensorimotor and neuromuscular responses. In addition, Curcumin administration protects rats against acetamiprid-induced cerebellum toxicity such as increase in AChE and BChE activities, decrease on cells viability, oxidative stress, and an increase of intracellular calcium. Taken together, these results demonstrate for the first time that ACE treatment substantially impairs the survival of primary neuronal cells through the induction of necrosis concomitantly with the generation of an oxidative stress. Additionally, curcumin reduced histopathological changes caused by ACE.

The immune system can be the target of many chemicals, with potentially severe adverse effects on the host's health. In the literature, carbamate (CM) pesticides have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate, or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, direct immunotoxicity, endocrine disruption and inhibition of esterases activities have been introduced as the main mechanisms of CMs-induced immune dysregulation. Moreover, the evidence on the relationship between CM pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers, allergies, autoimmune and infectious diseases is criticized. In addition, in this review, we will discuss the relationship between immunotoxicity and cancer, and the advances made toward understanding the basis of cancer immune evasion.

In the literature, carbamates pesticides (CMs) have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, oxidative stress and inhibition of esterases activities have been introduced as the main mechanisms of CMs induced immune dysregulation. In addition, the evidence on the relationship between CMs pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers are criticized. (C) 2016 Faculty of Health and Social Studies, University of South Bohemia in Ceske Budejovice. Published by Elsevier Sp. z o.o. All rights reserved.

N-acetylcysteine (NAC), a cysteine pro-drug and glutathione precursor has been used in therapeutic practices for several decades, as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication. There is a growing interest concerning the beneficial effects of NAC against the early stages of toxicity-induced by pesticides. Nevertheless, the mechanisms underlying the therapeutic and clinical applications of NAC are not fully understood. In this review we aimed to focus on the protective effects of NAC against oxidative stress caused by pesticide in many organs. The possible mechanisms of action may be associated to its antioxidant properties. The anti-oxidative activity of NAC has been attributed to the fast reaction with free radicals as well as the restitution of reduced glutathione (GSH).

Organophosphorus (OP) and carbamate (CM) pesticides are widely used in agriculture. These pesticides are highly toxic to humans and their residues in food pose potential threat to human health. In this comparative study, we investigated the effect of subchronic exposure of OPs (malathion, MAL) and CM (Carbosulfan, CB) on rat liver and spleen. Biochemical analysis showed that levels of hepatic enzymes (ALT, ALP, LDH and PAL) changed after exposure to the pesticides. In the liver extracts, lipid peroxidation index increased after the treatment by pesticides. Our results indicated that exposure to MAL and CB leads to alteration of liver redox status. Both pesticides induced focal inflammation and fibrosis in the liver. After subchronic administration of MAL (200 mg/kg) and CB (25 mg/kg), systemic inflammation, as depicted by the increase in IFN-δ activity in liver, was observed in both malathion and carbosulfan treated animals. In addition, the results showed that MAL significantly increased TCD4+ and TCD8+ lymphocyte number. It also decreased INF-δ and IL-4 production. However, CB induced a reduction of TCD8+ number and cytokine production in spleen cells. In conclusion, malathion and carbosulfan had significant immunomodulatory properties in the spleen with inflammation and oxidative stress induction in the liver.

The present study is designed to investigate the anti-inflammatory potential of N-acetylcysteine (NAC) against carbosulfan (CB)-induced hepatic dysfunction in rats. Rats exposed to CB and NAC were examined for toxicity by assessing various biochemical alteration, inflammation (interferon gamma and leucocyte counts), and peroxidation marker, including in liver. Significant increases of blood alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma glutamyltransferase (GGT) were detected in CB-treated rats. In addition, the level of pro-oxidative marker, such as malondialdehyde (MDA), was also increased. According to the results, rats exposed to CB showed a significant alteration in hepatic enzymes and an increase in the accumulation of lipid peroxidation index; also, CB induced an increase in pro-inflammatory cytokine in CB-treated rats when compared with their respective controls. Interestingly, administration of NAC to CB-treated rats attenuates the toxicity of CB, objectified by biochemical and oxidative improvement of liver. Thus, the present study reports for the first time that NAC could be a promising therapeutic agent against CB-induced liver impairment.

Imidacloprid (IMI) is known to target the nicotinic acetylcholine receptors (nAChRs) in insects, and potentially in mammals. However, IMI toxicity on mammalian tissues has not been adequately evaluated. The aim of the present study was to examine whether IMI induced functional impairment in hypthalamic-pituitary-adrenal (HPA) axis tissues. An oral exposure of 40 mg IMI/kg for 28 days in male rats caused a significant increase in malondialdehyde (MDA) level. The antioxidant catalase, superoxide dismutase, and glutathione S-transferase showed various alterations following administration, but a significantly depleted thiol (SH) groups was only recorded in hypothalamic tissues. The increase in the relative weight of adrenal glands and the increased adrenal cholesterol and plasma adrenocorticotropic hormone (ACTH) levels are indicative of general adaptation syndrome. The hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased, highlighting the alteration of cholinergic transmission. In conclusion, the findings obtained show that chronic exposure to IMI may alter biochemical processes of HPA axis.

Objective: N-acetylcysteine (NAC), a cysteine pro-drug and glutathione precursor has been used in therapeutic practices for several decades, as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication. There is a growing interest concerning the beneficial effects of NAC against the early stages of type-2 diabetes development. Nevertheless, the mechanisms underlying the therapeutic and clinical applications of NAC are not fully understood. In this review we aimed to focus on the protective effects of NAC against insulin resistance.Design and methods: The possible mechanisms of action were reviewed using the major findings of more than 100 papers relating to the antioxidant, anti-inflammatory and anti-apoptotic properties of NAC.Results: The anti-oxidative activity of NAC has been attributed to its fast reactions with free radicals as well as the restitution of reduced glutathione. Further, NAC has anti-inflammatory and anti-apoptotic properties which can have positive effects during the inflammatory process in insulin resistance. Moreover, NAC can modulate certain signaling pathways in both insulin target cells and beta cells.Conclusions: The diverse biological effects of NAC may make it a potential adjuvant or therapeutic target in the treatment of type-2 diabetes. So, further studies are required for determining its ability to alleviate insulin resistance and to improve insulin sensitivity. (C) 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

The present study investigated the protective effects of N-acetylcysteine (NAC), is widely known as an antidote to acetaminophen overdose, on carbosulfan (CB)-induced hematotoxicity and oxidative stress in male rats. CB was administered at a dose of 25 mg/kg or simultaneously administered with NAC (2 g/l) for 30 days. Results of hematological examination showed that red blood cells, hematocrite, hemoglobin, and reticulocytes levels were significantly lower in CB-exposed rats compared with those in the control. Administration of CB caused a significant increase in the superoxide dismutase and catalase activities. However, the glutathione (GSH) and thiols group (TSH) levels were significantly increased as well as GSH S-transferase activity and levels of glutathione peroxidase on erythrocytes of males rats compared with those in the control. Also, CB-treated rats showed significant elevation in lipid peroxidation (LPO) and acetylcholinesterase (AChE) on erythrocytes in comparison with the control. Co-administration with NAC exhibited chemoprotective effects against CB-mediated hematotoxicity, augmented erythrocyte antioxidant status, and prevented the induction of anemia.

Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-L-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

Objective(s):Lead (Pb) is a toxic metal inducing many destructive effects leading to a broad range of physiological, biochemical, and neurological dysfunctions in humans and laboratory animals. Materials and Methods: Here, we investigated the effect of chronic exposure to Pb (50 mg/l) on oxidative stress, hepatotoxicity, nephrotoxicity, and lipid profile of two different age groups of female rats treated with Pb from delivery until puberty period (40 days, Pb40) and post puberty period (65 days, Pb65). Results: Our results clearly show that the administration of Pb produces oxidative damage in liver and kidney, as strongly suggested by the significant increase in TBARS, decrease in total SH, and the alteration of SOD activity. Elevation in liver function biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and reduction in total protein (liver and plasma) and albumin are evidence of perturbations of liver synthetic function. In young Pb-treated group, Pb-induced nephropathy was more pronounced by the increase in the levels of creatinine, urea, and uric acid. However, hyperlipidemia was evident for both Pb-exposed groups leading to a potential risk for cardiovascular diseases and atherosclerosis. Conclusion: It is concluded that Pb induces metabolic and oxidative disturbances depending on the age of the animals, which are not negligible.

Several studies showed that organophosphorus pesticides disturb glucose homeostasis and can increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on glucose metabolism regulation, in vivo, during subchronic exposure. Malathion was administered orally (200 mg/kg), once a day for 28 consecutive days. Plasma glucose, insulin and Glycated hemoglobin levels were significantly increased while hepatic glycogen content was decreased in intoxicated animals compared with the control group. Furthermore, there was a significant disturbance of lipid content in subchronic treated and post-treated rats deprived of malathion for one month. In addition, we used the homeostasis model assessment (HOMA) to assess insulin resistance (HOMA-IR) and pancreatic beta-cell function (HOMA-beta). Our results show that malathion increases insulin resistance biomarkers and decreases insulin sensitivity indices. Statistical analysis demonstrates that there was a positive and strong significant correlation between insulin level and insulin resistance indices, HOMA-IR, HOMA-beta. Similarly, a negative and significant correlation was also found between insulin level and insulin sensitivity indices. For the first time, we demonstrate that malathion induces insulin resistance in vivo using homeostasis model assessment and these changes were detectable one month after the end of exposure. To explain insulin resistance induced by malathion we focus on lipid metabolism disturbances and their interaction with many proteins involved in insulin signaling pathways.

Carbosulfan (CB)-induced oxidative stress leads to the inevitable accumulation of free radicals and eventual alteration of antioxidant enzymes in various biological systems. The present study is designed to investigate the preventive effect of N-acetylcysteine (NAC) on carbosulfan-induced hepatic and renal dysfunction in rats. Rats exposed to CB and NAC were examined for toxicity by assessing various biochemical alteration and stress markers including in liver and kidney. Significant increases of blood alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyltransferase (GGT), creatinine and urea were detected in CB-treated rats. In addition, the levels of antioxidative enzymes such as catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) also were assessed. According to the results, rats exposed to carbosulfan showed a significant increase in the accumulation of stress markers and an alteration in the antioxidative enzymes activity, when compared to their respective controls. Interestingly, administration of NAC to CB-treated rats attenuates the toxicity of this compound, objectified by biochemical and oxidative improvement of liver and kidney. Thus, the present study reports for the first time that NAC could be a promising therapeutic agent against CB-induced oxidative stress.

The effect of Carbosulfan (CB), a carbamate insecticide which has been used widely in agriculture, was investigated using wistar rat.Carbosulfan was administered orally at sublethal concentration at a dose of 25 mg/kg to 12 male rats ad libitum during the tests for 30 days consecutively.The effect of CB on hematological constituent [Red Blood Corpuscules (RBC) , White Blood Corpuscules (WBC), Mean Cell Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC), platelet (PLT) Hemoglobin (HGB) and Hematocrit (HCT) levels] and serum damage marker enzymes [aspartate aminotransferase (AST), alanin aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)] of rats were investigated under laboratory conditions .Body weight, organ weight, cellularity of spleen, spleen cell subtypes, cytokine production and lymphocyte proliferation assay were also studied.CB treatments caused different effects on the hematological constituents and the serum marker enzymes of the treatment groups as compared to the controls.Results showed that CB-treated group had a significantly lower RBC, HGB, HCT, MCV, MCH and MCHC and significantly higher WBC and PLT.Also, serum marker enzymes were affected by CB.For example, ALT, ALP, creatinine and urea significantly increased in rats treated with CB.Our data showed that CB at 25 mg/kg/day could suppress cellular activity of the immune system.At this dose, CB significantly decreased the proliferation response to PHA and the production of IFN gamma and IL-4.

There is increasing evidence reporting that organophosphorus pesticides (OPs) impair glucose homeostasis and cause insulin resistance and type 2 diabetes. Insulin resistance is a complex metabolic disorder that defies explanation by a single etiological pathway. Formation of advanced glycation end products, accumulation of lipid metabolites, activation of inflammatory pathways and oxidative stress have all been implicated in the pathogenesis of insulin resistance. Ultimately, these molecular processes activate a series of stress pathways involving a family of serine kinases, which in turn have a negative effect on insulin signaling. Experimental and clinical data suggest an association between these molecular mechanisms and OPs compounds. It was first reported that OPs induce hyperglycemia. Then a concomitant increase of blood glucose and insulin was pointed out. For some years only, we have begun to understand that OPs promote insulin resistance and increase the risk of type 2 diabetes. Overall, this review outlines various mechanisms that lead to the development of insulin resistance by OPs exposure.

Organophosphorus pesticides are known to disturb glucose homeostasis and increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on insulin signaling pathways and the protective effects of N-acetylcysteine (NAC). Malathion (200 mg/kg) and NAC (2 g/l) were administered orally to rats, during 28 consecutive days. Malathion increases plasma glucose, plasma insulin and glycated hemoglobin levels. Further, we observed an increase of insulin resistance biomarkers and a decrease of insulin sensitivity indices. The GP, GSK3β and PEPCK mRNA expressions were amplified by malathion while, the expression of glucokinase gene is down-regulated. On the basis of biochemical and molecular findings, it is concluded that malathion impairs glucose homeostasis through insulin resistance and insulin signaling pathways disruptions in a way to result in a reduced function of insulin into hepatocytes. Otherwise, when malathion-treated rats were compared to NAC supplemented rats, fasting glucose and insulin levels, as well as insulin resistance indices were reduced. Furthermore, NAC restored liver GP and PEPCK expression. N-acetylcysteine showed therapeutic effects against malathion-induced insulin signaling pathways disruption in liver. These data support the concept that antioxidant therapies attenuate insulin resistance and ameliorate insulin sensitivity.

Insulin resistance and risk of type 2 diabetes are the most important complications following exposure to organophosphorous (OPs) pesticides. Regarding the importance of liver on metabolic pathways regulation, in particular blood glucose homeostasis, we focused on liver inflammation and oxidative damages in a subchronic model of toxicity by malathion. Adult male Wistar rats of body weight 200-250 g were used for the study. Malathion (200 mg/kg b.w./day) was administered to rats by oral intubation for 28 days. Glycemic and insulin resistance indices, markers of liver injury, markers of inflammation and oxidative stress were assessed. Malathion-treated rats showed increased glycemia, insulinemia and glycated hemoglobin level, HOMA-IR and HOMA-beta indices, plasma activities of hepatocellular enzymes, lipid peroxidation index, CD3(+)/CD4(+) and CD3(+)/CD4(+) and pro-inflammatory cytokines when decreased antioxidant status in liver was noted. Most of our study indicates that malathion promotes insulin resistance, inflammation and Hepatosteatosis in subchronic model of exposure. On the basis of biochemical and molecular findings, it is concluded that insulin resistance induced by malathion occurs through oxidative stress and related pro-inflammatory markers in a way to result in a reduced function of insulin in liver cells. (C) 2014 Elsevier B.V. All rights reserved.

Malathion toxicity has been related to the inhibition of acetylcholinesterase, induction of oxidative stress, liver damage and impairment of kidney function as well as hematotoxicity. N-acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the protective effect of NAC against toxic consequences of malathion exposure in Wistar rats. Malathion was given daily to rats via oral gavage and NAC in drinking water during seven days. When malathion-treated rats were compared with control, a leukocytosis and reduced hemoglobin (HGB) content were detected. Furthermore, malathion produced a significant increase in liver enzymes such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase and creatinine kinase. In addition, a decrease in acid phosphatase activity, protein and globulin levels were observed in malathion-treated rats compared with control. Moreover, analyses of the mineral status showed a disturbance in calcium, magnesium, phosphore and iron contents of the malathion-treated rats. Interestingly, NAC showed therapeutic effects against malathion toxicity. Indeed, HGB content and all liver enzymes were restored to normal values. Finally, the use of NAC as therapeutic agent for only seven days during malathion exposure showed interesting results on tissues damages.

Aims: Occupational exposure to organophosphate pesticides is becoming a common and increasingly alarming world-wide phenomenon. The present study is designed to investigate the preventive effect of N-acetylcysteine on malathion-induced hepatic injury and inflammation in rats.Main methods: Adult male Wistar rats of body weight 200-230 g were used for the study. Malathion (200 mg/kg b.w./day) was administered to rats by oral intubation and N-acetylcysteine (2 g/l) in drinking water for 28 days. Rats were sacrificed on the 28th day, 2 h after the last administration. Markers of liver injury (aspartate transaminase, alanine transaminase, alkaline phosphatase and lactate desyhdogenase), inflammation (leukocyte counts, myeloperoxidase, immunophenotyping of CD4(+) and CD8(+), interleukin-1 beta, interleukin-6 and interferon-gamma expression) and oxidative stress (lipid peroxidation, reduced glutathione and antioxidant status) were assessed.Key findings: Malathion induced an increase in activities of hepatocellular enzymes in plasma, lipid peroxidation index, CD3(+)/CD4(+) and CD3(+)/CD4(+) percent and pro-inflammatory cytokines, when decreased antioxidant status in liver was noted. When malathion-treated rats were compared to NAC supplemented rats, leukocytosis, T cell count and IL-1 beta, IL-6, INF-gamma expression were reduced. Furthermore, NAC restored liver enzyme activities and oxidative stress markers.Significance: Malathion induces hepatotoxicity, oxidative stress and liver inflammation. N-acetylcysteine showed therapeutic effects against malathion toxicity. (C) 2014 Elsevier Inc. All rights reserved.