Imen Ghorbel

Disruption of erythrocyte antioxidant defense system, hematological parameters, induction of pro-inflammatory cytokines and DNA damage in liver of co-exposed rats to aluminium and acrylamide

The individual toxic effects of aluminium and acrylamide are well known but there are no data on their combined effects. The present study was undertaken to determine (i) hematological parameters during individual and combined chronic exposure to aluminium and acrylamide (ii) correlation of oxidative stress in erythrocytes with pro-inflammatory cytokines expression, DNA damage and histopathological changes in the liver. Rats were exposed to aluminium (50 mg/kg body weight) in drinking water and acrylamide (20 mg/kg body weight) by gavage, either individually or in combination for 3 weeks. Exposure rats to AlCl3 or/and ACR provoked an increase in MDA, AOPP, H2O2 and a decrease in GSH and NPSH levels in erythrocytes. Activities of catalase, glutathione peroxidase and superoxide dismutase were decreased in all treated rats. Our results showed that all treatments induced an increase in WBC, erythrocyte osmotic fragility and a decrease in RBC, Hb and Ht. While MCV, MCH, MCHC remained unchanged. Hepatic pro-inflammatory cytokines expression including tumor necrosis factor-α, interleukin-6, interleukin-1β was increased suggesting leucocytes infiltration in the liver. A random DNA degradation was observed on agarose gel only in the liver of co-exposed rats to AlCl3 and ACR treatment. Interestingly, co-exposure to these toxicants exhibited synergism based on physical and biochemical variables in erythrocytes, pro-inflammatory cytokines and DNA damage in liver.

Co-exposure to aluminum and acrylamide disturbs expression of metallothionein, proinflammatory cytokines and induces genotoxicity: Biochemical and histopathological changes in the kidney of adult rats

The individual toxic effects of aluminum and acrylamide are known but there is no data on their combined effects. The present study investigates the toxic effects after combined exposure to these toxicants on: (i) oxidative stress during combined chronic exposure to aluminum and acrylamide on kidney function (ii) correlation of oxidative stress with metallothionein (MT) and inflammatory cytokines expression, DNA damage, and histopathological changes. Rats were exposed to aluminum (50 mg/kg body weight) in drinking water and acrylamide (20 mg/kg body weight) by gavage either individually or in combination for 3 weeks. Exposure rats to aluminum chloride or acrylamide alone and in combination induced nephrotoxicity, as evidenced by a decrease in the 24‐h urine volume and uric acid levels in plasma and an increase of plasma creatinine, urea, and blood urea nitrogen levels. Nephrotoxicity was objectified by a significant increase in malondialdehyde level, advanced oxidation protein, and protein carbonyl contents, whereas reduced glutathione, nonprotein thiol, vitamin C levels, catalase, and glutathione peroxidase activities showed a significant decline. Superoxide dismutase activity and its gene expression were increased. Aluminum and acrylamide co‐exposure exhibited synergism in various biochemical variables and also in DNA damage. Kidney total MT levels and genes expression of MT1, MT2, and proinflammatory cytokines were increased. All these changes were supported by histopathological observations. Co‐exposure to aluminum and acrylamide exhibited synergism and more pronounced toxic effects compared with their individual effects based on various biochemical variables, genotoxic, and histopathological changes.

Expression of metallothioneins I and II related to oxidative stress in the liver of aluminium-treated rats

Abstract Hepatotoxicity, induced by aluminium chloride (AlCl3), has been well studied but there are no reports about liver metallothionein (MT) genes induction. Therefore, it is of interest to establish the mechanism involving the relation between MT gene expression levels and the oxidative stress status in hepatic cells of aluminium-treated rats. Aluminium (Al) was administered to rats in their drinking water at a dose of 50 mg/kg body weight for three weeks. AlCl3 provoked hepatotoxicity objectified by an increase in malondialdehyde (MDA), hydrogen peroxide (H2O2), advanced oxidation protein products (AOPP), protein carbonyls (PCO) and a decrease in reduced glutathione (GSH), non-protein thiols (NPSH) and vitamin C. CAT and Glutathione peroxidase (GPx) activities were decreased while Mn-SOD gene expression, total Metallothionein content and MT I and MT II genes induction were increased. There are changes in plasma of some trace elements, albumin levels, transaminases, LDH and ALP activities. All these changes were supported by histopathological observations.

Penconazole alters redox status, cholinergic function, and membrane-bound ATPases in the cerebrum and cerebellum of adult rats:

Pesticides exposure causes usually harmful effects to the environment and human health. The present study aimed to investigate the potential toxic effects of penconazole, a triazole fungicide, on the cerebrum and cerebellum of adult rats. Penconazole was administered intraperitoneally to male Wistar rats at a dose of 67 mg kg−1 body weight every 2 days during 9 days. Results showed that penconazole induced oxidative stress in rat cerebrum and cerebellum tissues. In fact, we have found a significant increase in malondialdehyde, hydrogen peroxide, and advanced oxidation protein product levels, as well as an alteration of the antioxidant status, enzymatic (superoxide dismutase and catalase) and nonenzymatic (glutathione), the cholinergic function, and membrane-bound ATPases (Na+/K+-ATPase and Mg2+-ATPase). Penconazole also provoked histological alterations marked by pyknotic and vacuolated neurons in the cerebrum and apoptosis and edema in the cerebellum Purkinje cells’ layer. Therefore, the use of this neurotoxicant fungicide must be regularly monitored in the environment.

Improvement of kidney redox states contributes to the beneficial effects of dietary pomegranate peel against barium chloride-induced nephrotoxicity in adult rats

Abstract Context: Pomegranate (Punica granatum L., Punicaceae) is known to possess enormous antioxidant activity. Objective: This study investigates the protective effects of pomegranate peel against barium-mediated renal damage. Materials and methods: Rats were exposed during 21 days either to barium (67 ppm), barium + pomegranate peel (5% of diet) or to only pomegranate peel (5% of diet). Results: Exposure rats to barium provoked a significant increase in kidney malondialdehyde (MDA), advanced oxidation protein products (AOPP) and hydrogen peroxide (H2O2) levels. Creatinine, urea and uric acid levels in plasma and urine were also modified. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, non protein thiol (NPSH) and reduced glutathione (GSH) levels were decreased. Metallothionein (MT) production was increased and their genes expressions were up-regulated. All these changes were improved by dietary pomegranate peel. Moreover, the distorted histoarchitecture in kidney of barium group was alleviated by pomegranate peel. Conclusion: Our data showed, for the first time, the protective effects of pomegranate peel against barium-induced renal oxidative damage.

Effects of acrylamide graded doses on metallothioneins I and II induction and DNA fragmentation: Bochemical and histomorphological changes in the liver of adult rats

The present study investigates the toxic effects of acrylamide (ACR) administered to rats at two doses on (i) oxidative stress and disruption of pro-oxidant/antioxidant balance in hepatic cells and (ii) its correlation with metallothioneins (MTs) genes expression, DNA damage and histomorphological changes. Treated rats with 20 and 40 mg/kg body weight of ACR led to an increase in malondialdehyde, hydrogen peroxide, advanced oxidation protein products, protein carbonyl levels as well as an alteration in the antioxidant status. Total MT content in the liver and MT I and MT II genes induction were increased. Plasma transaminases activities, albumin, total protein and glucose levels were also increased, while alkaline phosphatase activity was decreased. Moreover, total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-C) levels, TC/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratios were increased, while HDL-C decreased in a dose-dependent manner. A random DNA degradation was observed only in the liver of ACR-treated rats with the highest dose. These changes were confirmed by histopathological observations.

Protective effects of dietary selenium and vitamin C in barium-induced cardiotoxicity.

Several metals including barium (Ba) known as environmental pollutants provoke deleterious effects on human health. The present work pertains to the potential ability of selenium (Se) and/or vitamin C, used as nutritional supplements, to alleviate the toxic effects induced by barium chloride (BaCl2) in the heart of adult rats. Animals were randomly divided into seven groups of six each: group 1, serving as negative controls, received distilled water; group 2 received in their drinking water BaCl2 (67 ppm); group 3 received both Ba and Se (sodium selenite 0.5 mg kg−1 of diet); group 4 received both Ba and vitamin C (200 mg kg−1 bodyweight) via force feeding; group 5 received Ba, Se, and vitamin C; and groups 6 and 7, serving as positive controls, received either Se or vitamin C for 21 days. The exposure of rats to BaCl2 caused cardiotoxicity as monitored by an increase in malondialdehyde, hydrogen peroxide, and advanced oxidation protein product levels, a decrease in Na+-K+ adenosine triphosphatase (ATPase), Mg2+ ATPase, and acetylcholinesterase activities and in antioxidant defense system (catalase, glutathione peroxidase, superoxide dismutase, glutathione, and nonprotein thiols). Plasma lactate dehydrogenase and creatine kinase activities, total cholesterol, triglyceride, and low-density lipoprotein–cholesterol levels increased, while high-density lipoprotein–cholesterol level decreased. Coadministration of Se and/or vitamin C restored the parameters indicated above to near control values. The histopathological findings confirmed the biochemical results. Se and vitamin C may be a promising therapeutic strategy for Ba-induced heart injury.

Penconazole alters redox status, cholinergic function and lung’s histoarchitecture of adult rats: Reversal effect of vitamin E

The present study pertains to the possible adverse effects of penconazole exposure on the lung of adult rats, and to the potential ability of vitamin E (Vit E) in mitigating the toxicity induced by this fungicide. Male Wistar rats were divided into four groups of six animals each: Group I (Controls): rats drank distilled water; Group II (PEN): rats received, by gavage, 50 mg/kg body weight (1/40 LD50) of penconazole every 2 days during 10 days; Group III (Vit E): rats received daily 100 mg α-tocopherol acetate/kg body weight during 10 days by gavage; and Group IV (Vit E + PEN): rats received both vitamin E (100 mg α-tocopherol acetate/kg body weight) and penconazole (50 mg/kg body weight), being vitamin E given as a daily dosage and penconazole every 2 days, by gavage during 10 days. Results showed that penconazole induced oxidative stress in the lung demonstrated by an increase in malondialdehyde (+77%), hydrogen peroxide (+58%) and advanced oxidation protein product (+22%) levels, as compared to the controls. Furthermore, a decrease in the activities of catalase (-41%), superoxide dismutase (-45%), glutathione peroxidase (-23%) and acetylcholinesterase (-67%), and an increase in the levels of non-protein thiols (+17%), glutathione (+7%) and vitamin C (+44%) were registered. Abnormalities in lung histological sections such as alveolar edema, infiltration of inflammatory cells (leukocytes) and emphysema, were also observed following penconazole exposure. Vitamin E ameliorated the biochemical parameters, as well as the histological impairments induced by this fungicide. In conclusion, our study demonstrated that vitamin E, a natural antioxidant, was effective in alleviating penconazole-induced lung damage in Wistar rats.

Zinc and selenium modulate barium-induced oxidative stress, cellular injury and membrane-bound ATPase in the cerebellum of adult rats and their offspring during late pregnancy and early postnatal periods

Abstract Context: Barium (Ba) may induce oxidative stress leading to tissues injury. Objective: Our study investigated the therapeutic efficiency of zinc (Zn) and selenium (Se) against neurotoxicity induced by Ba in adult rats and their progeny. Material and methods: Pregnant rats are exposed either to Ba (67 ppm), Ba + Zn, Ba + S or to only Zn and Se. Results: In Ba-treated rats, there was an increase of MDA, H2O2, AOPP levels and SOD activity in the cerebellum of dams and their pups, a decrease in GPx, CAT, AChE, Na+K+-ATPase and Mg2+-ATPase activities, GSH and NPSH levels. These changes were confirmed by histological damages. Co‐administration of Zn or Se to Ba-treated rats ameliorated the biochemical and histological aspects. Conclusion: Our results revealed that Zn and Se have shown promising effects against Ba toxicity in the cerebellum of adult rats and their suckling pups.

Effects of barium graded doses on redox status, membrane bound ATPases and histomorphological aspect of the liver in adult rats

Abstract Nowadays, liver diseases constitute a major health problem in the world. The objective of the present study was to elucidate the hepatotoxicity induced by barium chloride (BaCl2) administered at graded doses in order to evaluate redox state and membrane-bound ATPases in the liver of adult rats. Our results showed, after 21 days of treatment with barium at doses 67 150 and 300 ppm, an increase in hepatic biomarkers such as AST, ALT and GGT activities and in bilirubin and albumin levels. A significant increase in MDA, LOOHs, H2O2, AOPP and PCO levels in liver of treated rats with graded doses of BaCl2 was also observed suggesting the implication of oxidative stress with a significant relation between dose and response. Moreover, LDH activity increased in plasma and decreased in liver of all treated groups. Antioxidant activities of glutathione peroxidase and catalase decreased, especially with the highest dose of barium, indicating a failure of antioxidant system defense. Additionally, the activities of Na+K+-ATPase and Mg2+-ATPase significantly decreased in all treated groups. Our biochemical findings were supported by histological observations. These results highlight the subchronic hepatotoxicity of barium.