Awatef Elwej

Methyl-thiophanate increases reactive oxygen species production and induces genotoxicity in rat peripheral blood

Abstract Methylthiophanate is one of the widely used fungicides to control important fungal diseases of crops. The aim of this study was to elucidate the short-term hematoxicity and genotoxicity effects of methylthiophanate administered by intraperitoneal way at three doses (300, 500 and 700 mg/kg of body weight) after 24, 48 and 72 h. Our results showed, 24 h after methylthiophanate injection, a hematological perturbation such as red blood cells (p < 0.05, p < 0.05 and p < 0.01) and hemoglobin content (p < 0.05), respectively, and a noticeable genotoxic effect in WBC evidenced by a significant increase in the frequency of the micronuclei and a decrease in cell viability. An increase in erythrocyte osmotic fragility was also noted after 24 and 48 h of methylthiophanate treatment at graded doses. A significant increase in hydrogen peroxide, advanced oxidation of protein products and malondialdehyde levels, in erythrocytes of methylthiophanate-treated rats with 300, 500 and 700 mg/kg of body weight, was also observed after 24 h of treatment (p < 0.05, p < 0.01 and p < 0.001, respectively), suggesting the implication of oxidative stress in its toxicity. Antioxidants activities of superoxide dismutase and glutathione peroxidase in erythrocytes significantly increased (p < 0.001) 24 h after the highest dose injected. While all these parameters were improved after 72 h of methylthiophanate injection (300, 500 and 700 mg/kg body weight). In conclusion, these data showed that the exposure of adult rats to methylthiophanate resulted in oxidative stress leading to hematotoxicity and the impairment of defence system, confirming the pro-oxidant and genotoxic effects of this fungicide.

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.

Protective effects of pomegranate peel against hematotoxicity, chromosomal aberrations, and genotoxicity induced by barium chloride in adult rats

Abstract Context Pomegranate peel (PP) has health benefits including antibacterial, antioxidant, anti-inflammatory, and antimutagenic properties. Objective This study investigated the biochemical composition and protective effects of PP against hematotoxicity and genotoxicity induced by barium chloride (BaCl2) in adult rats. Materials and methods Adult Wistar rats were divided into four groups of six each: control, barium (67 ppm via drinking water), PP (5% via diet), and their combination during 21 d. Oxidative stress was determined by MDA, AOPP, and antioxidant status: CAT, GPx, GSH, Vit C. Osmotic fragility (OF), chromosomal aberrations (CAs), and micronucleus (MN) assays were also studied. Results PP showed a rich composition of antioxidant compounds. DPPH test found IC50 value= 5.3 μg/mL and a high polysaccharides content (315 ± 5 mg/g of extract). In vivo study showed a decrease in red blood cells (70%) and platelet counts (46%), hemoglobin content (8%), hematocrit percent (7%), and an 80% increase of white blood cells in Ba-treated rats. A reduction in antioxidant status: catalase, glutathione peroxidase activities, glutathione, and vitamin C levels by 31, 21, 28, and 29%, respectively, and an increase in MDA (46%) and AOPP levels (72%) were also observed compared with controls. BaCl2-treatment showed a significant increase in the frequencies of total chromosomal aberrations with abnormal metaphases and micronucleus in bone-marrow cells. Oxidative stress induced by BaCl2 might be the major cause for chromosomal abnormalities leading to DNA damage. Discussion and conclusion A decrease in hematotoxic and genotoxic effects induced by PP is due to its powerful antioxidant capacity.

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 co-exposure to imidacloprid and gibberellic acid on redox status, kidney variables and histopathology in adult rats

Abstract Data on the individual nephrotoxic effects of imidacloprid (IMI) and gibberellic acid (GA3) are scarce. Moreover, there is a lack of information about their combined effects on the renal tissue. Our study investigated the effects of IMI and GA3 separately or together on rats kidney. IMI (64 mg/kg bw) was given for 3 weeks by gavage either individually or in combination with GA3 (200 mg/L) via drinking water. IMI associated or no with GA3 increased the levels of kidney malondialdehyde, advanced oxidation protein products, protein carbonyls and metallothionein, plasma creatinine, urea, blood urea nitrogen and lactate dehydrogenase activity. A decline of kidney uric acid level and antioxidant status was also observed. All these changes were supported by histopathological observations. Our results highlighted the role of IMI and/or GA3-induced nephrotoxicity. Co-exposure to IMI and GA3 exhibited synergism in biochemical kidney variables and histopathology and antagonism in physical and morphological parameters.

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.