Najoua Gharbi

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.

Dietary virgin olive oil protects against lipid peroxidation and improves antioxidant status in the liver of rats chronically exposed to ethanol

Excessive ethanol intake induces severe tissue damage particularly in the liver through the generation of reactive oxygen species. The aim of this study was to determine the effect of a virgin olive oil-rich diet on oxidative stress induced by chronic ethanol exposure in rats. Wistar rats were treated daily with a 35% ethanol solution for 6 weeks and fed with a standard chow or a diet containing 5% virgin olive oil. By administering ethanol to rats, a severe toxicity occurred in their liver, as assessed by the significantly elevated levels of serum transaminases. The hepatic malondialdehyde level, indicator of lipid peroxidation, was also increased in ethanol-treated rats, whereas the hepatic antioxidant enzyme activities, namely, superoxide dismutase, glutathione peroxidase, and catalase were significantly reduced. The activity of glutathione reductase remained unchanged in rats. Fatty acid composition of the liver was also significantly changed with ethanol intake. In contrast, virgin olive oil intake during ethanol treatment in rats resulted in a higher antioxidant activity and inhibited toxicity to the liver, as monitored by the reduction of transaminases levels and hepatic lipid peroxidation. Rats showed a better profile of the antioxidant system with normal glutathione peroxidase activity and ameliorated superoxide dismutase and catalase activities. In conclusion, results of this study indicate that olive oil ingestion by rats protects the liver from ethanol-induced oxidative damage by affecting the cellular redox potential.

A review on the molecular mechanisms involved in insulin resistance induced by organophosphorus pesticides.

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.

Antioxidant and anti-inflammatory effects of N-acetylcysteine against malathion-induced liver damages and immunotoxicity in rats

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 (200mg/kg b.w./day) was administered to rats by oral intubation and N-acetylcysteine (2g/l) in drinking water for 28 days. Rats were sacrificed on the 28th day, 2h 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-1β, interleukin-6 and interferon-γ 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-1β, IL-6, INF-γ 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.

Effect of Age-Dependent Exposure to Lead on Hepatotoxicity and Nephrotoxicity in Male Rats

Lead is known to induce a broad range of physiological, biochemical, and behavioral dysfunctions in laboratory animals and humans. This includes age‐specific variations in absorption, retention, and tissue distribution of lead. This study was carried out to investigate the effects of chronic exposure to lead (50 mg/L) on liver and kidneys of two different age groups of male rats treated with lead from delivery until puberty period (40 days) and postpuberty period (65 days). For this purpose, the concentrations of thiobarbituric acid reactive substance (TBARS), total thiol groups (SH), and superoxide dismutase (SOD) activity were measured in the liver and kidney of rats. Renal function was analyzed by determining creatinine, acid uric, and urea. Plasma activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and albumin were determined spectrophotometrically to evaluate hepatic function. These markers of damage were determined to assess the level of toxicity in these animals. Our results clearly show that the administration of lead 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. In young lead‐exposed animals, lead‐induced perturbations on the synthetic function of the liver and the kidney were more pronounced. However, nephropathy is evident for adult lead‐exposed animals. It is concluded that lead induces severe hepatic and renal toxicity, which depends on the age of the animals and the target organ.

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.

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 β 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.