Olfa Tebourbi

Antidiarrheal and antioxidant activities of chamomile (Matricaria recutita L.) decoction extract in rats

ETHNOPHARMACOLOGICAL RELEVANCE Matricaria recutita L. (Chamomile) has been widely used in the Tunisian traditional medicine for the treatment of digestive system disorders. The present work aims to investigate the protective effects of chamomile decoction extract (CDE) against castor oil-induced diarrhea and oxidative stress in rats. METHODS The antidiarrheal activity was evaluated using castor oil-induced diarrhea method. In this respect, rats were divided into six groups: Control, Castor oil, Castor oil+Loperamide (LOP) and Castor oil+various doses of CDE. Animals were per orally (p.o.) pre-treated with CDE during 1h and intoxicated for 2 or 4h by acute oral administration of castor oil. RESULTS Our results showed that CDE produced a significant dose-dependent protection against castor oil-induced diarrhea and intestinal fluid accumulation. On the other hand, we showed that diarrhea was accompagned by an oxidative stress status assessed by an increase of malondialdehyde (MDA) level and depletion of antioxidant enzyme activities as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Castor oil also increased gastric and intestinal mucosa hydrogen peroxide (H2O2) and free iron levels. Importantly, we showed that chamomile pre-treatment abrogated all these biochemical alterations. CONCLUSION These findings suggested that chamomile extract had a potent antidiarrheal and antioxidant properties in rats confirming their use in traditional medicine.

Age modulates Fe3O4 nanoparticles liver toxicity: dose-dependent decrease in mitochondrial respiratory chain complexes activities and coupling in middle-aged as compared to young rats.

We examined the effects of iron oxide nanoparticles (IONPs) on mitochondrial respiratory chain complexes activities and mitochondrial coupling in young (3 months) and middle-aged (18 months) rat liver, organ largely involved in body iron detoxification. Isolated liver mitochondria were extracted using differential centrifugations. Maximal oxidative capacities (V max, complexes I, III, and IV activities), V succ (complexes II, III, and IV activities), and V tmpd, (complex IV activity), together with mitochondrial coupling (V max/V 0) were determined in controls conditions and after exposure to 250, 300, and 350 μg/ml Fe3O4 in young and middle-aged rats. In young liver mitochondria, exposure to IONPs did not alter mitochondrial function. In contrast, IONPs dose-dependently impaired all complexes of the mitochondrial respiratory chain in middle-aged rat liver: V max (from 30 ± 1.6 to 17.9 ± 1.5; P < 0.001), V succ (from 33.9 ± 1.7 to 24.3 ± 1.0; P < 0.01), V tmpd (from 43.0 ± 1.6 to 26.3 ± 2.2 µmol O2/min/g protein; P < 0.001) using Fe3O4 350 µg/ml. Mitochondrial coupling also decreased. Interestingly, 350 μg/ml Fe3O4 in the form of Fe3+ solution did not impair liver mitochondrial function in middle-aged rats. Thus, IONPs showed a specific toxicity in middle-aged rats suggesting caution when using it in old age.

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.

Nanotoxicological evaluation of oxidative responses in rat nephrocytes induced by cadmium.

The aim of this study was to investigate the interaction of cadmium chloride with mineral elements in rat nephrocytes in terms of the biosynthesis of nanocomplexes. The results show that selenium supplementation enhanced cadmium accumulation in kidneys. Analysis of the fluorescence revealed an increase in red fluorescence in the kidneys of rats co-exposed to cadmium and selenium. Interestingly, X-ray diffraction measurements carried out on kidney fractions of co-exposed rats point to the biosynthesis of cadmium selenide and/or sulfide nanoparticles (about 62 nm in size). Oxidative stress assays showed the ability of selenium to reduce lipid peroxidation and to restore glutathione peroxidase and superoxide dismutase activity in kidneys. Hence, cadmium complexation with selenium and sulfur at a nanoscale level could reduce oxidative stress induced by cadmium in kidneys.

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.

Protective effect of Artemisia campestris extract against aspirin-induced gastric lesions and oxidative stress in rat

The present study aims at evaluating the antiulcer and antioxidant effect of Artemisia campestris aqueous extract (ACAE) as well as the mechanism of action involved in such gastroprotection. The use of LC/MS allowed the identification of 11 phenolic compounds and the colorimetric analysis demonstrated that the ACAE exhibited an important in vitro antioxidant activity. We first showed that in vivo ACAE protected against macroscopic and histological changes induced by aspirin in stomach mucosa. Aspirin administration was accompanied by an oxidative stress status assessed by an increase in malondialdehyde (MDA) level, a decrease in the content of sulfhydryl –(SH) groups and a depletion of antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Pre-treatment with ACAE protected against aspirin-induced gastric oxidative stress. More importantly, aspirin administration increased plasma and tissue hydrogen peroxide (H2O2), free iron and calcium levels, while the ACAE pre-treatment reversed all the effects of aspirin-induced intracellular mediators. In conclusion, we suggest that Artemisia campestris aqueous extract has potent antiulcer and antioxidant properties. This gastroprotection offered by ACAE might be related partly to the safety of sulfhydryl group as well as its opposite effect on some intracellular mediators such as hydrogen peroxide, free iron and calcium.

Chemical composition, antioxidant properties and hepatoprotective effects of chamomile (Matricaria recutita L.) decoction extract against alcohol-induced oxidative stress in rat.

The present study assessed the chemical composition, antioxidant properties, and hepatoprotective effects of subacute pre-treatment with chamomile (Matricaria recutita L.) decoction extract (CDE) against ethanol (EtOH)-induced oxidative stress in rats. The colorimetric analysis demonstrated that the CDE is rich in total polyphenols, total flavonoids and condensed tannins, and exhibited an important in vitro antioxidant activity. The use of LC/MS technique allowed us to identify 10 phenolic compounds in CDE. We found that CDE pretreatment, in vivo, protected against EtOH-induced liver injury evident by plasma transaminases activity and preservation of the hepatic tissue structure. The CDE counteracted EtOH-induced liver lipoperoxidation, preserved thiol -SH groups and prevented the depletion of antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). We also showed that acute alcohol administration increased tissue and plasma hydrogen peroxide (H(2)O(2)), calcium and free iron levels. More importantly, CDE pre-treatment reversed all EtOH-induced disturbances in intracellular mediators. In conclusion, our data suggest that CDE exerted a potential hepatoprotective effect against EtOH-induced oxidative stress in rat, at least in part, by negatively regulating Fenton reaction components such as H(2)O(2) and free iron, which are known to lead to cytotoxicity mediated by intracellular calcium deregulation.

Phytochemical, antioxidant and protective effect of Rhus tripartitum root bark extract against ethanol-induced ulcer in rats.

Rhus tripartitum (sumac) is an Anacardiaceae tree with a wide phytotherapeutic application including the use of its roots in the management of gastric ulcer. In the present study the Rhus tripartitum root barks extract (RTE) was phytochemical studied, in vitro tested for their potential antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and reducing power assay and in vivo evaluated for its ability to prevent ethanol-induced gastric ulcer in rats. The RTE was rich in phenolics, flavonoids, tannins and polysaccharide contents and exhibited a low but not weak in vitro antioxidant activity when compared with (+)-catechin. Pre-treatment with RTE at oral doses 50, 200 and 400 mg/kg body weight was found to provide a dose-dependent protection against ethanol-induced ulcer by averting the deep ulcer lesions of the gastric epithelium, by reducing gastric juice and acid output, by enhancing gastric mucus production by preserving normal antioxidant enzymes activities, and inhibiting the lipid peroxidation. The antiulcerogenic activity of RTE might be due to a possible synergistic antioxidant and antisecretory effects.