Khémais Ben Rhouma

Evaluation of antioxidant and antiulcerogenic activities of Opuntia ficus indica f. inermis flowers extract in rats.

The Opuntia ficus indica f. inermis methanolic flowers extract (OMFE) was phytochemical studied, in vitro tested for their potential antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power, linoleic acid peroxidation assays and in vivo evaluated for its ability to prevent ethanol-induced gastric ulcer in rats. The OMFE was rich in polysaccharide, phenolics and flavonoids contents and exhibited a moderate in vitro antioxidant activity when compared with (+)-catechin and ascorbic acid. Pre-treatment with OMFE at oral doses 250, 500 and 1000 mg/kg body weight was found to provide a dose-dependent protection against ethanol-induced gastric ulcer by averting the deep necrotic lesions of the gastric epithelium, by preserving normal antioxidant enzymes activities, by inhibiting the lipid peroxidation, the oxidation of protein and the DNA fragmentation in gastric mucosa. The antiulcerogenic activity of OMFE might be due to a possible synergistic antioxidant and antihistaminic-like effects.

Antioxidant and antiulcerogenic activities of Opuntia ficus indica f. inermis root extract in rats.

Opuntia ficus indica f. inermis methanolic root extract (ORE) was investigated for phenolic and flavonoids contents, in vitro evaluated for DPPH radical scavenging activity, reducing power and in vivo tested for its gastro-protective ability against 80% ethanol induced ulcer in rats. Phytochemical test of ORE were positive for phenolic and flavonoid contents. DPPH radical scavenging activity and reducing power of ORE showed an EC(50) of 118.65±2.51 μg/ml and 300 μg/ml respectively. In vivo the pre-treatment of rats with ranitidine (50 mg/kg) and 200, 400, and 800 mg/kg doses of ORE significantly (p<0.05) reduced the 80% ethanol induced-ulcer lesion, with a rate of 82.68%, 49.21%, 83.13%, and 92.59% respectively, and prevented the depletion of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total glutathione (GSH), and inhibited the increase of myeloperoxidase (MPO) and malondialdehyde (MDA) in rat stomach tissues when compared with ethanol group. Also pre-treatment with ORE marked a dose-dependent attenuation of histopathology changes induced by ethanol. Phenolic and flavonoids wealth, radical scavenging activity, and reducing power, have been implicated for antiulcer property of ORE.

Influence of a static magnetic field (250 mT) on the antioxidant response and DNA integrity in THP1 cells

The aim of this study was to investigate the effect of static magnetic field (SMF) exposure in antioxidant enzyme activity, the labile zinc fraction and DNA damage in THP1 cells (monocyte line). Cell culture flasks were exposed to SMF (250 mT) during 1 h (group 1), 2 h (group 2) and 3 h (group 3). Our results showed that cell viability was slightly lower in SMF-exposed groups compared to a sham exposed group. However, SMF exposure failed to alter malondialdehyde (MDA) concentration (+6%, p>0.05) and glutathione peroxidase (GPx) (-5%, p>0.05), catalase (CAT) (-6%, p>0.05) and superoxide dismutase (SOD) activities (+38%, p>0.05) in group 3 compared to the sham exposed group. DNA analysis by single cell gel electrophoresis (comet assay) revealed that SMF exposure did not exert any DNA damage in groups 1 and 2. However, it induced a low level of DNA single strand breaks in cells of group 3. To further explore the oxidative DNA damage, cellular DNA for group 3 was isolated, hydrolyzed and analysed by HPLC-EC. The level of 8-oxodGuo in this group remained unchanged compared to the sham exposed group (+6.5%, p>0.05). Cells stained with zinc-specific fluorescent probes zinpyr-1 showed a decrease of labile zinc fraction in all groups exposed to SMF. Our data showed that SMF exposure (250 mT, during 3 h) did not cause oxidative stress and DNA damage in THP1 cells. However, SMF could alter the intracellular labile zinc fraction.

Effects of static magnetic field and cadmium on oxidative stress and DNA damage in rat cortex brain and hippocampus

The present study was undertaken to determine the effect of co-exposure to static magnetic field (SMF) and cadmium (Cd) on the antioxidant enzymes activity and DNA integrity in rat brain. Sub-chronic exposure to CdCl (CdCl2, 40 mg/L, per os) for 30 days resulted in a significant reduction in antioxidant enzyme activity such as the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in frontal cortex and hippocampus. Total GSH were decreased in the frontal cortex of the Cd-exposed group. Cd exposure induced an increase in malondialdehyde (MDA) concentration in the frontal cortex and hippocampus. Moreover, the same exposure increased 8-oxo-7,8-dihydro-2-desoxyguanosine (8-oxodGuo) level in rat brain. Interestingly, the combined effect of SMF (128 mT, 1 hour/day for 30 consecutive days) and CdCl (40 mg/L, per os) decreased the SOD activity and glutathione level in frontal cortex as compared with the Cd group. Moreover, the association between SMF and Cd increased MDA concentration in frontal cortex as compared with Cd-exposed rats. DNA analysis revealed that SMF exposure failed to alter 8-oxodGuo concentration in Cd-exposed rats. Our data showed that Cd exposure altered the antioxidant enzymes activity and induced oxidative DNA lesions in rat brain. The combined effect of SMF and Cd increased oxidative damage in rat brain as compared with Cd-exposed rats.

Effects of Sub-Acute Exposure to Static Magnetic Field on Hematologic and Biochemical Parameters in Pregnant Rats

This study investigated the effects of a static magnetic field (SMF) on hematopoiesis and biochemical parameters in female rats. Pregnant rats were exposed to SMF (128 mT–1 hour/day from day 6 to day 19 of pregnancy). At 25°C, the exposure of rats 1 hour/day for 13 consecutive days to SMF induced an increase in hematocrit (Ht) level (+6%, p < 0.05), hemoglobin (Hb) concentration (+12%, p < 0.05) and LDH levels (67%, p < 0.05 ), suggesting an hypoxia-like state. Moreover, exposure to SMF increased blood glucose and decreased insulin release, leading to a diabetic-like state in pregnant rats.

Effects of hexavalent chromium on reproductive functions of male adult rats

Hexavalent chromium is an environmental contaminant which may be associated with reproductive abnormalities in male rats. In the present study, we examined the effect of hexavalent chromium on male reproductive function of rats. Male Wistar rats received a daily intraperitoneal injection of potassium dichromate (1 or 2 mg/kg body weight) for fifteen consecutive days. A decrease in testis weight and an increase in seminal vesicles and prostate weights were demonstrated after chromium treatment. Moreover, a dose-dependent increase in blood and testis chromium levels as well as an increase in FSH and a decrease in LH and testosterone serum levels were detected in treated rats. Histological analysis revealed pronounced morphological alterations with enlarged intracellular spaces, tissue loosening and dramatic loss of gametes in the lumen of the seminiferous tubules of treated rats. In addition, a decreased sperm motility and number of epididymal spermatozoa together with an increased sperm abnormality rate was found in chromium-treated rats in comparison to controls. In rats receiving the higher chromium dose, histological images presented considerably increased areas filled with seminal vesicle and prostate secretions. The mucosal crypts of seminal vesicles and the typical invaginations of prostate were altered. The results suggest that subacute treatment of potassium dichromate promotes reproductive system toxicity and affects testicular function of adult male rats.

Embryotoxicity and fetotoxicity following intraperitoneal administrations of hexavalent chromium to pregnant rats

Heavy metals are omnipresent in the environment, and industrial use has greatly increased their presence in soil, water and air. Their inevitable transfer to the human food chain remains an important environmental issue as many heavy metals cause a range of toxic effects, including developmental toxicity. Administration of chromium VI (1 and 2 mg/kg as potassium dichromate) through intraperitoneal (i.p.) injection during organogenesis (days 6 to 15 of gestation) in rats revealed embryo- and fetotoxic effects. Reduced fetal weight, retarded fetal development, number of fetuses per mother and high incidences of dead fetuses and resorptions in treated mothers were also observed. Gross morphological abnormalities, such as displayed form of edema, facial defect, lack of tail, hypotrophy, severs subdermal haemorrhage patches and hypotrophy of placenta were observed in fetuses after chromium VI-treated mothers. A skeletal development of fetuses presented an incomplete ossification in nasal, cranium, abdominal or caudal bones in rats treated with 1 mg/kg of chromium, whereas rats treated with 2 mg/kg showed ossification and absence of the sacral vertebrae compared with the control. At a higher dose of chromium, histological changes were found in fetuses with atrophy of theirs vital organs. Placental histological observations revealed a pronounced morphological alteration, with atrophy of decidual cells, a degenerated of chorionic villi and hypertrophy of blood lacuna. The present study suggests a risk to the developing embryo when the mother is exposed to a high concentration of chromium VI during organogenesis.

Molecular Mechanisms of Pesticide Toxicity

The environment represents a key contributor to human health and disease. Exposure to many environmental stressors such as pesticides have detrimental effects on health and are considered to contribute substantially to most diseases of major public health significance. Pesticide toxicity has been clearly demonstrated to alter a variety of physiological functions. In addition, evidence suggests that pesticide exposure increases the risk of cancer and neurodegenerative diseases. Recent evidence also demonstrates the ability of pesticides to act as endocrine disruptors, contributing to various adverse effects associated with reproductive and developmental toxicity (Colborn, 2006; Eskenazi et al., 1999). Thus, it is now evident that research towards understanding how pesticides influence the development and progression of disease will lead to further improvements in public health. A key for Environmental Sciences is identifying and understanding the basic biological processes that are altered or regulated by environmental factors, and that stimulate disease processes to begin, or the course of the disease to be substantially altered. For this, basic biology research with potential for future translation into the clinic must be pursued to understand the fundamental changes caused by exposure to environmental agents especially pesticides that will drive the scientific basis for health decisions. Cells respond and adapt to environmental signals such as toxicants or stressors through multiple mechanisms that involve communication pathways or signal transduction processes. A number of receptors sense the presence of foreign compounds in the cell and induce a cascade of events that is intended to lead to neutralization and excretion of these compounds. However, in many cases the metabolism of xenobiotic substances can give rise to toxic metabolites or to reactive oxygen species (ROS) that can harm the cell further. Additionally, the metabolism of foreign compounds can disturb other essential processes in the body, such as production and metabolism of certain hormones. Alterations in biochemical systems are often more sensitive indicators than those at higher levels of biological organization. Indeed, changes at the molecular level will underlie the effects at higher levels of organization. In this chapter, we focus on a number of molecular pathways implicated in responses to pesticides. In many cases, these responses are adaptive. However, the same systems are involved in reactions leading to toxic effects. They are crucial to the health effects associated with pesticide insult and can be linked to adverse toxic effects and pathologies at higher levels of organization. These systems are: Endocrine disruption that can take place at different physiological levels: A) Altering (inhibiting or stimulating) the secretion of hormones. This possible effect is related to

Metabolism of DDT in Different Tissues of Young Rats

The bioconcentration and distribution pattern of p,p′-DDT 1,1,1-1trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)-ethane] and its main metabolites (p,p′-DDD [1,1-dichloro-2,2-bis (4-chlorophenyl) ethane] and p,p′-DDE [1,1-dichloro-2,2-bis (4-chlorophenyl) in adipose tissue, liver, brain, kidney, thymus, and testis were examined in young rats after 10 days of intraperitoneal injection of 50 and 100 mg of p,p′-DDT/kg of body weight. Analyses were performed by high-resolution gas chromatography. p,p′-DDT was found to be accumulated in a dose-dependent manner with the highest concentration in adipose tissue. However, in brain, the accumulation of pesticide was low and remained unchanged at the higher dose. This difference may relate to the protective role of the blood-brain barrier, which limits the access of the xenobiotic in the cerebral compartment, and to the differential tissue lipid composition. Although tissues concentration of p,p′-DDE and p,p′-DDD correlated positively to total p,p′-DDT levels, the active role in detoxification of pollutants may explain why p,p′-DDD is more abundant in liver than in the rest of organs. On the contrary, in brain, the concentration of p,p′-DDE is higher than that of p,p′-DDD, suggesting that the metabolism of the parent insecticide proceeds via more than one pathway.

Ameliorative effect of Opuntia ficus indica juice on ethanol-induced oxidative stress in rat erythrocytes.

The aim of the present study was to investigate the efficacy of Opuntia ficus indica f. inermis fruit juice (OFIj) on reversing oxidative damages induced by chronic ethanol intake in rat erythrocytes. OFIj was firstly analyzed with HPLC for phenolic and flavonoids content. Secondly, 40 adult male Wistar rats were equally divided into five groups and treated for 90 days as follows: control (C), ethanol-only 3 g/kg body weight (b.w) (E), low dose of OFIj 2 ml/100 g b.w+ethanol (Ldj+E), high dose of OFIj 4 ml/100 g b.w+ethanol (Hdj+E), and only a high dose of OFIj 4 ml/100g b.w (Hdj). HPLC analysis indicated high concentrations of phenolic acids and flavonoids in OFIj. Ethanol treatment markedly decreased the activities of erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and the level of reduced glutathione (GSH). Changes in the erythrocytes antioxidant ability were accompanied by enhanced oxidative modification of lipids (increase of malondialdeyde level) and proteins (increase in carbonyl groups). Interestingly, pre-administration of either 2 ml/100 g b.w or 4 ml/100 g b.w of OFIj to ethanol-intoxicated rats significantly reversed decreases in enzymatic as well as non enzymatic antioxidants parameters in erythrocytes. Also, the administration of OFIj significantly protected lipids and proteins against ethanol-induced oxidative modifications in rat erythrocytes. The beneficial effect of OFIj can result from the inhibition of ethanol-induced free radicals chain reactions in rat erythrocytes or from the enhancement of the endogenous antioxidants activities.