Oxidative stress and histopathological changes induced by methylthiophanate, a systemic fungicide, in blood, liver and kidney of adult rats

Background: Methyl-thiophanate (MT), a fungicide largely used in agriculture throughout the world including Tunisia, protects many vegetables, fruits and field crops against a wide spectrum of fungal diseases. Oxidative stress has been proposed as a possible mechanism involved in MT toxicity on non-target organism.Methods: In the present study, the effect of MT injected intraperitoneally to adult rats at 300 or 500 mg/kg of body weight was studied on blood, liver and kidney.Results: Our results showed 3 days after MT injection, a significant decrease in hemoglobin and hematocrit values. A disruption in total white blood cells and platelets also occurred. Accordingly, an increased in malondialdehyde, H2O2 and advanced oxidation protein levels in liver and kidney were noted with the two doses. A significant change in plasma biomarkers and organ enzymatic and non-enzymatic activities were observed after MT treatment. The modifications in biochemical parameters were substantiated by histopathological data.Conclusion: These data confirmed the pro-oxidant effects of this fungicide. Accordingly, care must be taken to avoid mammalian and human exposure to MT.Keywords: Methyl-thiophanate, white blood cells, red blood cells, liver, kidne

Oxidative stress and histopathological changes induced by methylthiophanate, a systemic fungicide, in blood, liver and kidney of adult rats.

Background: Methyl-thiophanate (MT), a fungicide largely used in agriculture throughout the world including Tunisia, protects many vegetables, fruits and field crops against a wide spectrum of fungal diseases. Oxidative stress has been proposed as a possible mechanism involved in MT toxicity on non-target organism. Methods: In the present study, the effect of MT injected intraperitoneally to adult rats at 300 or 500 mg/kg of body weight was studied on blood, liver and kidney. Results: Our results showed 3 days after MT injection, a significant decrease in hemoglobin and hematocrit values. A disruption in total white blood cells and platelets also occurred. Accordingly, an increased in malondialdehyde, H2O2 and advanced oxidation protein levels in liver and kidney were noted with the two doses. A significant change in plasma biomarkers and organ enzymatic and non-enzymatic activities were observed after MT treatment. The modifications in biochemical parameters were substantiated by histopathological data. Conclusion: These data confirmed the pro-oxidant effects of this fungicide. Accordingly, care must be taken to avoid mammalian and human exposure to MT

Étude de la toxicité induite par le thiaméthoxame sur les paramètres morphologiques, hématologiques et sur l’équilibre oxydant/antioxydant chez des rats de souche Wistar [Study of the toxicity induced by thiamethoxam on morphological and hematological parameters and on the oxidant/antioxidant balance in Wistar rats]

Introduction. L’utilisation excessive des pesticides pose un véritable problème de santé publique, non seulement pour les personnes qui y sont exposées, mais aussi pour l’écosystème. Objectif. Etudier la toxicité induite par le thiaméthoxame (TMX) sur les paramètres morphologiques et hématologiques et sur les marqueurs du stress oxydatif au niveau des érythrocytes. Matériel et méthodes. Des rats mâles de souche Wistar ont été traités par voie intra-péritonéale pendant 30 jours avec trois doses croissantes de TMX (100, 150 et 300 mg/kg de poids corporel). Résultats. L’exposition des rats au TMX a provoqué une perturbation du comportement des rats, de leur poids corporel et de leur consommation quotidienne de nourriture et de boisson. De plus, des modifications du profil hématologique caractérisées par une anémie accompagnée de thrombopénie généralement liée à un déficit immunitaire, ont été détectées. Toutes ces altérations du profil hématologique sont confirmées par l’observation microscopique du frottis sanguin des différents groupes de rats. De plus, une altération du système de défense antioxydante, caractérisée par une diminution du glutathion réduit (GSH), de l’activité la catalase (CAT), de la superoxyde dismutase (SOD) et de la glutathion pero-xydase (GPx), ainsi qu’une augmentation au niveau des marqueurs du stress oxydatif, tels que le malondialdéhyde (MDA) et les produits d'oxydation avancée des protéines (AOPP), est notée, témoignant de l’effet déstabilisant du TMX. Conclusion. Cette toxicité augmente avec l’élévation de la dose de TMX, reflétant que l’utilisation irrationnelle de cet insecticide peut affecter la santé des mammifères. [Introduction. The excessive use of pesticides poses a real public health problem, not only for the people who are exposed to them, but also for the ecosystem. Objective. To elucidate the effect of thiamethoxam-induced toxicity (TMX) on morpho-logical and hematological parameters, and on oxidative stress markers in erythrocytes. Material and methods. Male Wistar rats were treated intraperitoneally for 30 days with three increasing doses of TMX (100, 150 and 300 mg/kg body weight). Results. The exposition of the rats to TMX caused a disturbance in their behavior, their body weight, and their daily food and drink intake. In addition, a perturbation in the hematological profile was noted. In fact, anemia accompanied with thrombocytopenia usually related to an immune deficiency was also detected. All these alterations in the blood profile were ascertained by the microscopic observation of the blood smear for the different groups of rats. Moreover, an impairment of the antioxidant defense system characterized by a decrease in the reduced glutathione (GSH), the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), and by an increase in the level of oxidative stress markers, such as malondialdehyde (MDA) and advanced oxidation products of proteins (AOPP), was noted testifying the destabilizing effect of TMX. Conclusion. This toxicity increases with enhanced doses of TMX, reflecting that the irrational use of this insecticide can affect the health of mammals.

Bioactivity of <i>Falkenbergia rufolanosa</i> Methanolic Extract: Assessment of Its Effect on Methyl-Thiophanate Induced Bone and Blood Disorders

This study aimed to evaluate the potentiality of a mineral and antioxidant-rich methanolic extract of the red marine alga Falkenbergia rufolanosa (FRE) against methyl-thiophanate (MT)-induced toxicity in adult rats. The animals were allocated into four groups: controls, MT (300 mg/kg), MT + FRE, and FRE-treated group for 7 days. Our results demonstrated severe mineral perturbations due to MT treatment, especially in calcium and phosphorus levels in plasma, urine, and bone. Similarly, the hematological analysis revealed increased red blood cells, platelets, and white blood cells associated with striking genotoxicity. Interestingly, a significant rise in lipid peroxidation and advanced oxidation protein products level in erythrocytes and bone were noted. Meanwhile, a depletion of the antioxidant status in both tissues occurred. These biochemical alterations were in harmony with DNA degradation and histological variation in bone and blood. In the other trend, data showed that treatment with alga improved MT-induced hematotoxicity, genotoxicity, and oxidative stress in the blood and bone. Osteo-mineral metabolism and bone histo-architecture were also noted. In conclusion, these findings demonstrated that the red alga Falkenbergia rufolanosa is a potent source of antioxidant and antibacterial agents, as revealed by the in vitro analysis

Extra Virgin olive oil mitigates hematotoxicity induced by acrylamide and oxidative damage in adult rats

Acrylamide (ACR) is a dietary contaminant derived from a wide range of foods through the Maillard-reaction during the cooking process. The present study focused on the hematotoxic effects of ACR and the protective efficacy of Extra Virgin olive oil (EVOO) in alleviating hematotoxicity and oxidative stress in erythrocytes of adult rats. Rats were divided into four groups of six each: group 1, serving as negative controls, received distilled water; group 2 received by&nbsp; gavage ACR at a dose of 40 mg/ kg body weight; group 3 received by gavage ACR supplemented with EVOO (300 &mu;L); group 4,serving as positive controls, received only EVOO by gavage. All groups were sacrificed after three weeks. Acrylamide induced a significant increase in white blood cells (WBC), erythrocyte osmotic fragility (OF) and a decrease in red blood cells (RBC), hemoglobin (Hb) and hematocrit (Ht). While mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and MCH concentration (MCHC) remained unchanged. Furthermore, exposure of rats to ACR induced erythrocytes oxidative stress with an increase of malondialdehyde, hydrogen peroxide, and protein carbonyls levels. A reduction in antioxidant status, enzymatic (catalase, glutathione peroxidase and superoxide dismutase) and non enzymatic (reduced glutathione, non protein thiols and vitamin C) was observed when compared to controls. EVOO supplementation alleviated significantly hematotoxicity induced by acrylamide as evidenced by restoring the biochemical markers cited above to near normal values. Our results revealed that extra virgin olive oil, a main component of olive Mediterranean diet, was effective in preventing erythrocytes damage and oxidative stress