Saloua El-Fazaa

Bisphenol A and human chronic diseases: current evidences, possible mechanisms, and future perspectives.

Bisphenol-A (BPA) is one of the highest volume chemicals produced worldwide, with over 6billion pounds produced and over 100t released into the atmosphere each year. Recent extensive literature has raised concerns about its possible implication in the etiology of some human chronic diseases such as diabetes, obesity, reproductive disorders, cardiovascular diseases, birth defects, chronic respiratory and kidney diseases and breast cancer. In this review, we present the highlighted evidences on the relationship between BPA exposure and human chronic diseases and we discuss its eventual mechanisms of action, especially genetic, epigenetic and endocrine disruption mechanisms with the possible involvement of oxidative stress, mitochondrial dysfunction and cell signaling.

Metabolic disorders of acute exposure to malathion in adult Wistar rats.

Malathion is a widely organphosphorus insecticide used in agriculture, which shows strong insecticidal effects. However, the use of this insecticide leads to disruption in metabolic pathways. The aim of this study is to evaluate the acute effects of malathion on metabolic parameters in Wistar rats. Malathion was administered orally to rats at a dose of 400mg/kg body weight dissolved in corn oil. Glucidic and lipidic status were analyzed in plasma, cholinesterase activities were also determined. Malathion induces a transitory hyperglycaemia which correlated with depletion on glycogen content. Plasma triglycerides and LDL level increased significantly in malathion treated-rats. HDL rate was unchanged and cholesterol plasma content decrease transitory but rapidly reached a normal level. Results of this study indicate, clearly, that malathion in acute exposure leads to a disruption of lipid metabolism with an enhancement in LDL and triglyceride contents and may play an important role in the development of atherosclerosis and cardiovascular disease. Disruption in plasma lipid profile may leads to a kind of insulin resistance which results in hyperglycaemia.

A minireview on N-acetylcysteine: An old drug with new approaches.

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).

Biochemical evaluation of hepatic damage in subchronic exposure to malathion in rats: Effect on superoxide dismutase and catalase activities using native PAGE

The aim of this study was the evaluation of the hepatic damages following a subchronic exposure to malathion, an organophosphorus (OP) insecticide. Malathion was administered intragastrically in 1 ml corn oil containing 100 mg/kg Body Weight daily for 32 days. Malondialdehyde (MDA) concentration superoxide dismutase (SOD) and catalase (CAT) activities were analysed using a non-denaturing electrophoresis. The serum activities of Pseudocholinesterase (PchE), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) were determined. Malathion exposure leads to a significant decrease in AchE activity, an increase in hepatic MDA, and in serum ASAT and ALAT activities. A positive correlation between serum transaminases levels and hepatic MDA was demonstrated. These results indicate that malathion exposure induced lipid peroxidation LPO, a process of degradation of membrane lipids, involving the deterioration of the cellular integrity. We have recorded a slight increase in antioxidant enzymes activities. This leads us to suggest an insufficient elimination of free radicals, causing cytotoxic effects.

Potential protective effect on key steroidogenesis and metabolic enzymes and sperm abnormalities by fenugreek steroids in testis and epididymis of surviving diabetic rats

The current study showed that the daily oral treatment of fenugreek steroids, designated F(steroids), to diabetic rats during 30 days demonstrated a significant (p < 0.05) decrease of blood glucose level and a considerable increase of the area of insulin-immunoreactive β-cells in diabetic rats. Interestingly, this study showed that F(steroids) potentially unregulated the key steroidogenesis enzymes such as 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), malic enzyme, 3β-hydroxysteroid dehydrogenase (3β-HSD) and glucose-6-phosphate dehydrogenase (G6P-DH) activities as cholesterol rate in testis, which considerably enhanced testosterone and estradiol levels in the plasma of surviving diabetic rats. More interestingly, F(steroids) obviously prevented the alteration of the key carbohydrate enzymes such as hexokinase and pyruvate kinase activities as well as testicular glycogen and seminal fructose contents in surviving diabetic rats. Furthermore, F(steroids) administration to surviving diabetic rats significantly decreased the sperm shape abnormality and improved the sperm count. Above all, the potential protective action of reproductive systems was approved by the histological study of testis and epididymis.

Malathion exposure modulates hypothalamic gene expression and induces dyslipedemia in Wistar rats

Exposure to organophosphate (OP) pesticides is virtually ubiquitous. These inevitable agents are neurotoxicants, but recent evidence also points to lasting effects on carbohydrate metabolism. The aim of this study was to investigate the effects of 32 repeated treatment days with malathion, an OP insecticide, on some molecular and metabolic parameters. Malathion at 100 mg/kg was administered by gavage in Wistar rats. Results of this study indicate a significant decrease in hypothalamic corticotropin-releasing hormone mRNA, of malathion-treated rats. This result, in accordance with that of diabetic type 2 rat model, may be due to very potent negative feedback effects of glucocorticoids on hypothalamo-pituitary-adrenal (HPA) axis activity. In addition, we have recorded a significant increase in hypothalamic inducible NO synthase mRNA which probably enhances the negative feedback. These alterations are accompanied with hypertriglyceridemia that may be a favourable condition to insulin resistance. Thus, results of the present study suggest that malathion can be considered as an important risk factor in the development of diabetes type 2, which prevalence increased substantially in our country and around the world. Clearly, we need to focus further research on the specific incidences of hazardous food chemical contaminant that might be contributing to epidemic health perspectives.

Caffeic acid attenuates malathion induced metabolic disruption in rat liver, involvement of acetylcholinesterase activity.

It has been confirmed that organophosphorus compounds OP altered glucose homeostasis. Considerable experimental and clinical evidences have contributed the beneficial effects of polyphenol molecules on metabolic homeostasis. However, up to date limited studies have been performed on this topic. The aim of this study was to evaluate whether caffeic acid, an active phenolic component was able to reduce metabolic disruption induced by malathion administration. Malathion at 100mg/kg was administered to rats alone or in combination with caffeic acid at100 mg/kg. Malathion decreases hepatic GP activity and increases HK activity accompanied with a rise in the hepatic glycogen rate. Moreover, coadministration of malathion with caffeic acid resulted in restoration of malathion-induced GP inhibition and HK1 increase. These results may be due to the significant increase recorded in acetylcholinesterase (AchE) activity in vivo after coadministration of malathion and caffeic acid. Indeed, malathion is known to inhibit AChE activity leads to subsequent activation of cholinergic receptor that increased in part, catecholamine and glucocorticoids secretion; provoked glycogenolysis and gluconeogenesis activation. Thus, we can suggest that increases (AchE) activity seems to be responsible for caffeic acid restoration on malathion-induced metabolic disruptions. Recent studies support the hypothesis that oxons bind to a secondary site on acetylcholinesterase, leading to activation/inhibition of the catalytic site. Thus, caffeic acid or its derivates may be leading to activation of the catalytic site within the second site interaction.

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.

From immunotoxicity to carcinogenicity: the effects of carbamate pesticides on the immune system

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.

Immunosuppression and oxidative stress induced by subchronic exposure to carbosulfan in rat spleen: immunomodulatory and antioxidant role of N-acetylcysteine

Abstract The present study was designed to determine the immunosuppressive effects of carbosulfan (CB) and their relationship with an increased formation of reactive oxygen species in rat. Further, we aimed to evaluate the protective effects of N-acetyl-cysteine (NAC) against immunopathological changes induced by CB. Carbosulfan (25 mg/kg) and NAC (2 g/l) were given daily to rats during 30 days, via oral gavage and drinking water, respectively. Cell-mediated immune function, cytokines production, biomarkers of cell redox state maintenance, lipid peroxidation and the activities of antioxidant enzymes were measured in the spleen. Our data showed an increase in WBC percent (28.42%), a reduction in spleen CD8 T-lymphocytes (−85.63%) and a decrease in immunosuppressive cytokines production such as INF-gamma and IL-4. There was a switch from Th1-type to Th2-type cytokines with an unbalance toward anti-inflammatory cytokines. Moreover, a significant decrease in reduced glutathione (−71.68%) and total thiols (−39.81%) levels were observed in treated rats. Conversely, malondialdehyde level in spleen was increased (−42.3%), while glutathione-S-transferase, glutathione peroxidase, superoxide dismutase and catalase activities were depleted. Our results suggest that subchronic CB administration affects cellular enzyme and non-enzyme-mediated antioxidant defense systems and promotes immunotoxicity in rat. On the other hand, our data showed protective effects of NAC. Indeed, there was a recovery of oxidative stress markers and cytokines production. The use of NAC, in our study, as a therapeutic agent showed interesting results against CB toxicity.