Date seeds alleviate behavioural and neuronal complications of metabolic syndrome in rats.

Unhealthy dietary habits can play a crucial role in metabolic damages, promoting alteration of neural functions through the lifespan. Recently, dietary change has been perceived as the first line intervention in prevention and/or treatment of metabolic damages and related diseases. In this context, our study was designed to assess the eventual therapeutic effect of date seeds administration on memory and learning and on neuronal markers in a rat Metabolic Syndrome model. For this purpose, 32 adult male Wistar rats were fed with standard diet or high-fat high-sugar diet during ten weeks. After this, 16 rats were sacrified and the remaining rats received an oral administration of 300 mg of date seeds/kg of body weight during four supplementary weeks. Before sacrifice, we evaluate cognitive performances by the Barnes maze test. Afterwards, neuronal, astrocytic, microtubular and oxidative markers were investigated by immunoblotting methods. In Metabolic syndrome rats, results showed impairment of spatial memory and histological alterations. We identified neuronal damages in hippocampus, marked by a decrease of NeuN and an increase of GFAP and pTau396. Finally, we recorded an increase in protein oxidation and lipid peroxidation, respectively identified by an up-regulation of protein carbonyls and 4-HNe. Interestingly, date seeds administration improved these behavioural, histological, neuronal and oxidative damages highlighting the neuroprotective effect of this natural compound. Liquid Chromatography-Mass Spectrometry (LC-MS) identified, in date seeds, protocatechuic acid, caffeoylshikimic acid and vanillic acid, that could potentially prevent the progression of neurodegenerative diseases, acting through their antioxidant properties.

Spermatogenesis and steroidogenesis disruption in a model of metabolic syndrome rats.

CONTEXT: Metabolic syndrome (MetS) is a clustering of several physiological alterations. OBJECTIVE: This study was designed to evaluate the effects of MetS on rats spermatogenesis and steroidogenesis. MATERIALS AND METHODS: We developed a MetS rodent model using high-sugar and high-fat diet. RESULTS: MetS rats showed severe disorders in sperm parameters. Interestingly, a significant increase in malondialdehyde level and a decrease in the antioxidant activities were observed. Moreover, qRT-PCR analysis showed Bax down-regulation and Bcl-2 up-regulation. A decrease in testosterone level was identified, correlated with the CYP11A1, CYP17A1 and 17ß HSD testicular marker down-regulation. Finally, MetS rats showed an up-regulation of pro-inflammatory cytokines receptors IL-1R and IL-6R. CONCLUSION: MetS induced severe testis toxicity in male rats. Mets markedly distorted sperm parameters, inhibited the transcription of steroidogenic enzymes and led to oxidative stress, inflammation, and alteration of Bax/Bcl-2 ratioin testicular tissues.

Semen Parameter Alteration, Histological Changes and Role of Oxidative Stress in Adult Rat Epididymis on Exposure to Electronic Cigarette Refill Liquid.

Electronic cigarettes (e-cigarettes) are devices intended to substitute conventional cigarettes, with the aim of being less harmful. In a previous report, we showed that intraperitoneal (i.p.) injection of e-cigarette liquid (E-liquid), with or without nicotine, induced toxicity in the testes of Wistar rats by disrupting oxidative balance and steroidogenesis. In the present work, we further evaluated the impact of e-liquid with or without nicotine on the epididymis of rats using the same procedure. Results showed that e-liquid treatments led to alteration of semen parameters, with a significant drop of at least 50% in sperm vitality, a significant increase of morphologically abnormal spermatozoa and an imbalance of redox status in comparison to the control group. A significant raise of 1.4 fold, compared to the untreated rats, in myeloperoxidase (MPO) granules after both treatments was recorded, suggesting an inflammatory state. Histopathological examination confirmed a marked reduction in sperm count in the cauda epididymis. Data of this study suggest that the pro-oxidant properties of e-liquid with or without nicotine, in addition to testicular defects, could lead to an inflammatory state in the epididymis, causing alterations in the semen parameters. These data provide additional information on the impact of e-liquid on the reproductive system.

Neuroprotective effects of curcumin against acetamiprid-induced neurotoxicity and oxidative stress in the developing male rat cerebellum: biochemical, histological, and behavioral changes.

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.

Specific immune responses in mice following subchronic exposure to acetamiprid.

AIMS: Acetamiprid (ACE) is an insecticide of the neonicotinoid family, the most widely used in the world. Herein, we assessed the effect of ACE on either the humoral or cellular immune responses of rodents. We also evaluated the role of curcumin in the restoration of altered immune responses after ACE treatment. METHODS: Five groups of five Swiss Albino mice were immunized intraperitoneally with the recombinant form of CFP32, a virulence factor of Mycobacterium tuberculosis. One group received ACE (5mg/kg) during 61days, a second one received ACE associated with curcumin (100mg/kg). Three control groups were included; one untreated, the second received corn oil and the third received curcumin alone. The humoral immune response was assessed by ELISA testing the anti-rCFP32 antibody concentrations in the serum. The cellular immune response was assessed by analyzing the cellular proliferation of the splenocytes stimulated in vitro by a mitogen or rCFP32. RESULTS: The ACE-treated mice showed a significant immunosuppression of the specific humoral response with a restorative effect of curcumin when administered with ACE. Similarly, ACE significantly decreased the level of splenocyte proliferation after either a non specific or a specific activation. Curcumin partially restores the antigen specific cellular immune response. Moreover, when administered alone, curcumin significantly inhibits the proliferative responses to the mitogen confirming its anti-mitogenic effect. Histological analysis showed alteration of spleens of mice exposed to ACE. SIGNIFICANCE: Altogether, our data indicated that ACE could potentially be harmful to the immune system.

Prophylactic and curative effect of rosemary leaves extract in a bleomycin model of pulmonary fibrosis.

CONTEXT: Pulmonary fibrosis is a devastating disease without effective treatment. Rosemary is appreciated since ancient times for its medicinal properties, while biomolecules originated from the plant have an antioxidant and antifibrotic effect. OBJECTIVE: The effects of Rosmarinus officinalis L. (Lamiaceae) leaves extract (RO) on bleomycin-induced lung fibrosis were investigated. MATERIALS AND METHODS: Male Wistar rats were given a single dose of bleomycin (BLM, 4 mg/kg, intratracheal), while RO (75 mg/kg, intraperitoneal) was administered 3 days later and continued for 4 weeks (BLM/RO1-curative group). Alternatively, RO was administered 2 weeks before BLM and continued 15 days thereafter (BLM/RO2-prophylactic group). Antioxidant activities of RO and lung tissues were studied by standard methods. Histological staining revealed lung architecture and collagen deposition. RO was characterized for its polyphenol content and by high-performance liquid chromatography. RESULTS: RO polyphenol content was 60.52 mg/g of dry weight, carnosic and rosmarinic acids being major components (6.886 and 2.351 mg/g). Antioxidant effect of RO (DPPH and FRAP assay) expressed as IC50 values were 2.23 µg/mL and 0.074 µg/mL, respectively. In BLM/RO1 and BLM/RO2 lung architecture was less compromised compared to BLM, which was reflected in lower fibrosis score (2.33 ± 0.33 and 1.8 ± 0.32 vs 3.7 ± 0.3). Malondialdehyde levels were attenuated (141% and 108% vs 258% of normal value). Catalase and glutathione-S-transferase activities were normalized (103% and 117% vs 59%, 85% and 69% vs 23%, respectively). DISCUSSION AND CONCLUSION: RO has a protective effect against BLM-induced oxidative stress and lung fibrosis due to its phenolic compounds.

Impact of e-cigarette refill liquid with or without nicotine on liver function in adult rats.

This study was conducted to evaluate the effects of e-cigarette refill liquid administration alone or with nicotine on the antioxidant defense status, functional and histopathological changes in adult rat liver tissue. For this purpose, 32 rats were treated for 28 days as follows: control group was injected intra-peritoneally with physiological saline; e-cigarette 0% treated group received an intra-peritoneal injection of e-liquid without nicotine diluted in physiological saline, e-cigarette-treated group received an intra-peritoneal injection of e-liquid containing 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline and nicotine-treated group received an intra-peritoneal injection of 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline. In e-liquid without nicotine-exposed group, activities of the liver biomarkers aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase increase. Interestingly, oxidative stress indicators showed decreased total protein content, associated with a reduction in the antioxidant enzymes activities superoxide dismutase, catalase and glutathione-S-transferase, and an elevation in malondialdehyde content, highlighting the promotion of lipid peroxidation and oxidative stress. Histological studies identified inflammatory cells infiltration and cell death. Thus, e-liquid seems to promote oxidative tissue injuries, which in turn lead to the observed histopathological finding. In comparison, nicotine alone induced less oxidative stress and less histopathological disorders, whereas e-liquid with nicotine gave rise to more histopathological injuries. Thereby, e-liquid, per se, is able to induce hepatotoxicity and supplementation with nicotine worsens this state.

Neurobehavioral assessment following e-cigarette refill liquid exposure in adult rats.

The present study was conducted to assess the toxic effect of e-cigarette refill liquid on cognitive and motor functions in adult rats. Animals were administered 28 µl/kg of body weight of e-liquid with/without a dose of 0.5 mg of nicotine/kg of body weight, using the intraperitoneally route for a period of 4 weeks. They were then evaluated by novel object recognition test (NORT) and spontaneous alternation T-maze test for cognitive functions. Results indicated that e-liquid without nicotine induced, in the NORT, a decrease in time exploring the novel object during the test session and lower discrimination and recognition indexes compared to control and e-liquid with nicotine treated rats. Furthermore, short-term spatial memory was affected after e-liquid treatment in the spontaneous alternation T-maze test, identifying recognition memory impairments. However, none of the treatments altered motor functions assessed by inclined plane test, Kondziela's inverted screen test and weights test. Cell cytotoxicity assessment following e-liquid exposure showed a significant decrease in hippocampal cell viability, but no change in cortical cell viability. Thereby, e-liquid without nicotine causes cognitive impairments, especially on the hippocampus. Based on these results, more extensive assessments on e-cigarettes must be carried out.

Impact of e-cigarette refill liquid exposure on rat kidney.

Electronic-cigarettes (e-cigarette), the alternative to classic cigarettes are becoming extremely popular but their safety is not still established. Recent studies have showed cytotoxic effects of the electronic cigarette and its recharge e-liquid, in vitro. The present study was designed to evaluate e-cigarette liquid nephrotoxicity in rats. For this purpose, 32 rats were treated for 28 days as follows: Control group was injected intraperitoneally with NaCl 9 g/l; e-cigarette 0% treated group received an intraperitoneal injection of e-liquid without nicotine diluted in NaCl 9 g/l, e-cigarette treated group, received an intraperitoneal injection of e-liquid containing 0.5 mg of nicotine/kg of body weight/day diluted in NaCl 9 g/l and nicotine-treated group received an intraperitoneal injection of 0.5 mg of nicotine/kg of body weight/day diluted in NaCl 9 g/l. In nicotine group, creatinine level was increased, whereas urea and acid uric levels were decreased. In e-liquid-exposed groups, levels of uric acid and mainly urea were lower. Interestingly, after e-liquid exposure, oxidative stress status showed increased total protein and sulfhydril content, whereas superoxide dismutase and catalase activities were decreased. However, the levels of lipid peroxides were not increased after e-liquid exposure. Histological studies identified excess of cells with reduced and dark nuclei exclusively located in the renal collecting ducts. Thus, e-liquid seems to alter anti-oxidant defense and to promote minor changes in renal function parameters. This preliminary study raises some flags about possible nephrotoxicity of e-cigarette liquids in rats. As some features observed in rats may not be observed in human smokers, additional studies are needed to further qualify conclusions that might be applicable to actual users of e-cigarettes.

Comparison between electronic cigarette refill liquid and nicotine on metabolic parameters in rats.

AIMS: Nicotine is known to promote body weight loss and to disturb glucose homeostasis and lipoprotein metabolism. Electronic cigarettes, as a substitute to nicotine, are becoming increasingly popular, although there is no evidence regarding their safety. Considering the dearth of information about e-cigarette toxicity, the present study was designed to compare nicotine alone to e-liquid with or without nicotine on metabolic parameters in Wistar rats. MAIN METHODS: For this purpose, e-liquid with or without nicotine and nicotine alone (0.5mg/kg of body weight) were administered intra-peritoneally during 28 days. KEY FINDINGS: Our results show a significant decrease in food and energy intake after nicotine or e-liquid with nicotine exposure, when compared to control or e-liquid without nicotine. Analysis of lipid status identified a significant decrease in cholesterol and LDL levels in e-cigarette groups, suggesting an improvement in lipid profile. Interestingly, e-liquid without nicotine induced hyperglycemia which is negatively correlated to hepatic glycogen level, acting like nicotine alone. Furthermore, an increase in liver biomarkers was observed in all treated groups. qRT-PCR analysis showed GSK3ß up-regulation in e-liquid with nicotine as well as, surprisingly, in e-liquid without nicotine exposure. In contrast, PEPCK genes were only up-regulated in e-liquid with nicotine. SIGNIFICANCE: While some features observed in rats may not be observed in human smokers, most of our data are consistent with, e-liquid per se i.e. without nicotine, not being neutral from a metabolic stand point since disrupting glucose homeostasis in rats.

Disruption of steroidogenesis after dimethoate exposure and efficacy of N-acetylcysteine in rats: an old drug with new approaches.

Organophosphates (OPs) like dimethoate (DMT), are pesticides used worldwide, which can affect both animals and human. Whereas their toxicity is due to acetylcholinesterase inhibition, their secondary toxic effects have been related to free oxygen radical biosynthesis. The present study was designed to investigate the reprotoxic effects of DMT and the protective role of N-acetylcysteine (NAC) in male rat. DMT (20 mg/ kg/body weight) was administered daily to rats via gavage in corn oil and NAC (2 g/l) was added to drinking water for 30 days. Rats were sacrificed on the 30th day, 2 h after the last administration. Markers of testis injury (steroidogenesis impairment) and oxidative stress (lipid peroxidation, reduced glutathione, and antioxidant status) were assessed. In DMT-exposed rats, the serum level of testosterone was decreased. Further, a significant increase in lipid peroxidation level and a significant decrease in the activities of antioxidant enzymes were observed in the testis of rats during DMT intoxication. Real-time PCR (RT-PCR) analysis demonstrated a decrease in messenger RNA (mRNA) levels for testicular steroidogenic acute regulatory StAR protein, cytochrome P450scc, 3ß-hydroxysteroid dehydrogenase (3ß-HSD), and 17ß hydroxysteroid dehydrogenase (17ß-HSD) in the testis after DMT exposure. No significant changes in the oxidative stress status and selected reproductive variables were observed on CTN group, whereas NAC restored the oxidative stress and the steroidogenesis on NAC group. Dimethoate induces reprotoxicity and oxidative stress. N-acetylcysteine showed therapeutic recovery effects against dimethoate toxicity.

A comparative study on toxicity induced by carbosulfan and malathion in Wistar rat liver and spleen.

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.

Effects of dimethoate in male mice reproductive parameters.

The aim of the current study was to investigate the ability of dimethoate (DMT) to induce reprotoxicity in male mice. The dose (20 mg/kg/day) was given orally for 30 days. A significant decrease in sperm count, motility and viability and a significant increase of morphologically abnormal spermatozoa percent in DMT treated mice was observed. Testicular Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) activities were inhibited. Also, a significant increase in lipid peroxidation level and a significant decrease in the activities of antioxidant enzymes were observed in testis of DMT mice. In addition, gene expression of glutathione peroxidase 4 (GPx4) was quantified in RNA samples extracted from the testis by real-time reverse transcription-polymerase chain reaction (RT-PCR). Compared with control, mRNA expression of GPx4 was slightly decreased after DMT-exposure.

Carbosulfan-induced oxidative damage following subchronic exposure and the protective effects of N-acetylcysteine in rats.

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.

Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

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.

A review on the possible molecular mechanism of action of N-acetylcysteine against insulin resistance and type-2 diabetes development.

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 ß 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.

Changes in glucose metabolism and reversion of genes expression in the liver of insulin-resistant rats exposed to malathion. The protective effects of N-acetylcysteine.

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, GSK3ß 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.

Protective effects of caffeic acid against hypothalamic neuropeptides alterations induced by malathion in rat.

Exposure to pesticides is suspected to cause human health problems. Our study aimed to evaluate preventive effects of caffeic acid (3,4-dihydroxycinnamic acid) in the hypothalamus against malathion-induced neuropeptides gene expression alterations. Malathion at 100 mg/kg was administered intragastrically to rats alone or in combination with caffeic acid at 100 mg/kg during 4 weeks. A molecular expression of hypothalamic neuropeptides and plasmatic cholinesterase activity was investigated. Furthermore, we used in silico analysis, known as computational docking, to highlight the nature of acetylcholinesterase-malathion/caffeic acid interactions. Our findings showed differences in the responses and indicate that caffeic acid reversed malathion-induced decrease in corticotropin-releasing hormone mRNA but not brain-derived neurotrophic factor which presented an increased tendency. We suggest that caffeic acid can interact with acetylcholinesterase as the primary target of organophosphorus compounds. Results predict that caffeic acid can block partly the acetylcholinesterase gorge entrance via π-π stacking interaction with Tyr 124 and Trp 286 residues of the peripheral site leading to its stricture. Under this condition, we suggested that acetylcholine trafficking toward the catalytic site is ameliorated compared to malaoxon according to their sizes.

Oxidative stress and alteration of biochemical markers in liver and kidney by malathion in rat pups.

The present study was undertaken to determine the effects of malathion exposure through maternal milk on oxidative stress, functional an metabolic parameters in kidney and liver of rat pups. We found that lactational exposure to malation (200 mg/kg, body weight (bw)) induced an oxidative stress status assessed by an increase in malondialdhyde (MDA) content, reflecting lipoperoxidation, a decrease in thiol groups' content as well as depletion of enzyme activities as a superoxide dismutase (SOD) and catalase (CAT) on postnatal days (Pnds) 21 and 51. Moreover, the current study showed that malathion induced liver and kidney dysfunctions demonstrated by considerable increase in phosphatase alkaline (PAL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as total and direct bilirubin, creatinine urea and acid uric contents. We also observed an increase in triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and a decrease in high-density lipoprotein cholesterol (HDL-C) in the plasma of treated rat pups. These findings evidenced that malathion exposure during lactation through maternal milk of rats pups induced kidney and liver oxidative stress as well as functional and metabolic disorders that play a role in the development of others pathologies as cardiovascular diseases and cancers.

Lipid metabolism disturbances contribute to insulin resistance and decrease insulin sensitivity by malathion exposure in Wistar rat.

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 ß-cell function (HOMA-ß). 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-ß. 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.