Bessem Mornagui

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.

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.

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.

Influence of nitric oxide synthase inhibition on vasopressin and corticosterone secretion during water deprivation in rats

Nitric oxide (NO) is a short-lived radical that functions as a neurotransmitter in the central nervous system and plays a physiological role in the regulation of hypothalamic–pituitary–adrenal axis and vasopressinergic axis. In the present study, we aimed to investigate the interaction between the generation of NO and vasopressin (AVP) and corticosterone release after 3xa0days of water deprivation in rats. Animals were previously treated with intraperitoneal (i.p.) saline or l-nitro-arginine methyl ester (L-NAME) injection. l-NAME is a nonspecific inhibitor of nitric oxide synthases. In control rats given i.p. saline or l-NAME, hypothalamic, pituitary, and plasma AVP levels and plasma corticosterone did not change from baseline levels (pu2009>u20090.05). Three days of water deprivation increased significantly the corticosterone levels in plasma (pu2009<u20090.01) and AVP levels in hypothalamus and plasma (pu2009<u20090.01), but not in pituitary, which showed a significant decrease. These variations were concomitant with the elevation of nitrates/nitrates in plasma. l-NAME injection abolished significantly (pu2009<u20090.01) the elevation of plasma corticosterone and hypothalamic AVP levels induced by water deprivation. These findings showed that in water-deprived rats, nitric oxide synthase inhibition by l-NAME inhibits corticosterone and vasopressin release, suggesting a potent stimulatory role of NO.