Zohra Haouas

Oxidative Stress, Biochemical and Histopathological Alterations in the Liver and Kidney of Female Rats Exposed to Low Doses of Deltamethrin (DM): A Molecular Assessment

OBJECTIVE To evaluate histopathological alterations of the liver and kidney of female rats exposed to low doses of DM and its potential genotoxic activity. METHODS Female Wistar rats were randomly assigned to control (3 groups, 6 rats in each) and treatment groups (3 groups, 6 rats in each). They were subjected to subcutaneous injections of DM (at doses of 0.003, 0.03, and 0.3 mg/kg bw/d) after 30, 45, and 60 d, respectively. RESULTS Significant alterations were recorded in liver parenchyma induced by hepatic vacuolization, fragmented chromatin in nuclei, dilatation of sinusoids and congestions. Lesions within proximal and distal tubules were observed in the kidneys. Tissue congestions and severe alterations within glomeruli were visible. DM as a pyrethroid insecticide induced significant increase (P≤0.05) of plasma MDA concentrations after 45 d. A significant increase (P≤0.05) in plasma ALT (after 45 and 60 d) and AST (after 60 d) concentrations was recorded as compared to controls. During the whole experimental period the toxic agent provoked significant DNA damages (P≤0.05), especially in the dominance of classes 3 and 4 of obtained comet. CONCLUSION DM even at a very low dose displays harmful effects by disrupting hepatic and renal function and causing DNA damages in puberscent female rats. Low doses of DM are hepatotoxic and nephrotoxic.

Multimarker approach analysis in common carp Cyprinus carpio sampled from three freshwater sites.

The aim of this study is to assess the response of a multimarker approach in common carp Cyprinus carpio sampled from three Tunisian dam lakes selected according to different environmental and ecological characteristics. Glutathione-S-transferase (GST) activity was analyzed in carp liver and used as a phase II detoxification enzyme, hepatic metallothionein content (MTs) was used as a metallic stress indicator, and cholinesterase activities were analyzed in muscle and brain and used as neurotoxicity biomarker. Micronucleus frequency test (MN) as a genotoxicity marker. GST and MT levels showed an increase in fish from the Bir Mcherga site and a decrease in Sidi Saâd site with respect to fish from Nebhana site. Results showed a strong inhibition of cholinesterase activities in fish from Bir Mcherga and Sidi Saâd sites compared to Nebhana site. Relatively high level of MN is reported specially in fish blood from the Bir Mcherga site.

Study of lipid profile and parieto-temporal lipid peroxidation in AlCl3 mediated neurotoxicity. modulatory effect of fenugreek seeds

BackgroundPeroxidation of lipid (LPO) membrane and cholesterol metabolism have been involved in the physiopathology of many diseases of aging brain. Therefore, this prospective animal study was carried firstly to find out the correlation between LPO in posterior brain and plasmatic cholesterol along with lipoprotein levels after chronic intoxication by aluminium chloride (AlCl3). Chronic aluminum-induced neurotoxicity has been in fact related to enhanced brain lipid peroxidation together with hypercholesterolemia and hypertriglyceridemia, despite its controversial etiological role in neurodegenerative diseases. Secondly an evaluation of the effectiveness of fenugreek seeds in alleviating the engendered toxicity through these biochemical parameters was made.ResultsOral administration of AlCl3 to rats during 5 months (500 mg/kg bw i.g for one month then 1600 ppm via the drinking water) enhanced the levels of LPO in posterior brain, liver and plasma together with lactate dehydrogenase (LDH) activities, total cholesterol (TC), triglycerides (TG) and LDL-C (Low Density Lipoproteins) levels. All these parameters were decreased following fenugreek seeds supplementation either as fenugreek seed powder (FSP) or fenugreek seed extract (FSE). A notable significant correlation was observed between LPObrain and LDL-C on one hand and LDHliver on the other hand. This latter was found to correlate positively with TC, TG and LDL-C. Furthermore, high significant correlations were observed between LDHbrain and TC, TG, LDL-C, LPObrain as well as LDHliver.ConclusionAluminium-induced LPO in brain could arise from alteration of lipid metabolism particularly altered lipoprotein metabolism rather than a direct effect of cholesterol oxidation. Fenugreek seeds could play an anti-peroxidative role in brain which may be attributed in part to its modulatory effect on plasmatic lipid metabolism.

Fenugreek seeds, a hepatoprotector forage crop against chronic AlCl3 toxicity

BackgroundHaving considered how bioavailable aluminium (Al) may affect ecological systems and animals living there, especially cattle, and in search for a preventive dietary treatment against Al toxicity, we aimed to test the protective role of fenugreek seeds against chronic liver injury induced by aluminum chloride (AlCl3) in Wistar rats.ResultsFive months of AlCl3 oral exposure (500 mg/kg bw i.g for one month then 1600 ppm via drinking water) caused liver atrophy, an inhibition of aspartate transaminase (AST), alanine transaminase (ALT) and glutamyl transpeptidase (GGT), an enhancement of both lipid peroxidation and lactate dehydrogenase (LDH) activity and an increase of total protein level in liver. Moreover, histopathological and histochemical examinations revealed moderate alterations in the hepatic parenchyma in addition to a disrupted iron metabolism. Co-administration of fenugreek seed powder (FSP) at 5% in pellet diet during two months succeeded to antagonize the harmful effects of AlCl3 by restoring all tested parameters.ConclusionThis study highlighted the hepatotoxicity of AlCl3 through biochemical and histological parameters in one hand and the hepatoprotective role of fenugreek seeds on the other hand. Thus this work could be a pilot study which will encourage farmers to use fenugreek seeds as a detoxifying diet supplement for domestic animals.

Anemia and genotoxicity induced by sub-chronic intragastric treatment of rats with titanium dioxide nanoparticles.

Titanium dioxide nanoparticles (TiO2 NPs) are widely used for their whiteness and opacity. We investigated the hematological effects and genotoxicity of anatase TiO2 NPs following sub-chronic oral gavage treatment. TiO2-NPs were characterized by X-ray diffractometry (XRD), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). Wistar rats were treated with anatase TiO2 NPs by intragastric administration for 60 days. Hematological analysis showed a significant decrease in RBC and HCT and a significant increase in MCV, PLT, MPV and WBC at higher doses. Furthermore, abnormally shaped red cells, sometimes containing micronuclei, and hyper-segmented neutrophil nuclei were observed with TiO2 NPs treatment. The micronucleus test revealed damage to chromosomes in rat bone marrow at 100 and 200mg/kg bw; the comet assay showed significant DNA damage at the same doses.

Fenugreek seeds reduce aluminum toxicity associated with renal failure in rats

Despite the reports on safety concerns regarding the relationship between aluminum salts and neurological and bone disease, many countries continue to use aluminum as phosphate binders among patients with renal failure. In search for a diet supplement that could reduce aluminum toxicity related to renal failure, we carried out this prospective animal study in which the fenugreek seeds were assessed for their effects on rats nephrotoxicity induced by aluminum chloride (AlCl3). Oral AlCl3 administration during 5 months (500 mg/kg bw i.g for one month then 1600 ppm via drinking water) led to plasma biochemical changes, an inhibition of alkaline phosphatase (ALP), a decrease of total antioxidant status (TAS), and an induction of lipid peroxidation (LPO) in the blood and brain, in addition to kidney atrophy and morphological alterations at the level of Bowmans capsule, the glomerulus and different sorts of tubules, reminiscent of some known kidney disease. The treatment with the whole fenugreek seed powder (FSP) (5% in the diet) during the last 2 months showed its effectiveness in restoring normal plasma values of urea, creatinine, ALP and glucose, as well as re-increasing the TAS, inhibiting LPO and alleviating histopathological changes in the injured kidneys. This study highlights the induced nephrotoxicicity, as well as the related toxicity in the brain and bone, by chronic oral ingestion of the aluminum salts. However, the maintenance of a diet supplemented with fenugreek seeds could offer protection for the kidney, bone and brain, at the same time.

Assessment of Oxidative Stress and Histopathological Biomarkers in the Parablennius Incognitus Fish as Potential Contamination Indicators of the Bay of Sousse (Tunisia)

Oxidative stress and histopathological biomarkers were investigated in the gills and liver of Parablennius incognitus fishes. Individuals sampled in the bay of Sousse were compared to fishes from a reference site, i.e. Ghdamsi Island (Tunisia). Severe biochemical and histological alterations were observed in fishes from Sousse bay and associated with urban discharges contamination. Several tissue alterations were also observed in gills, particularly lamellar epithelium detachment, disorganization of pillar cells, and hypertrophy of chloride cells. In the liver we noted particularly hypertrophy of hepatocytes, congestion and dilation of the central vein and sinusoid capillaries, pyknotic nucleus, and hepatic steatosis. The high reduction of superoxide dismutase and catalase activities in gills and of superoxide dismutase and glutathione peroxidase activities in the liver of contaminated fishes may explain the increase of lipoperoxidation in both organs of P. incognitus. The integrated biomarker response values found in individuals from the contaminated site were in good agreement with alteration of physico-chemical parameters and with the high level of Cd concentrations detected in water of the stressful place, i.e. the bay of Sousse. Oxidative stress and histopathological alterations were sensitive biomarkers to discriminate between fishes from the polluted Sousse bay site and those from the reference site, suggesting their potential utility in bio monitoring.

Circadian variation in murine hepatotoxicity to the antituberculosis agent «Isoniazide»

The circadian time is an important process affecting both pharmacokinetics and pharmacodynamics of drugs. Consequently, the desired and/or undesired effects vary according to the time of drug administration in the 24 h scale. This study investigates whether the toxicity in liver as well as oxidative stress varies according to the circadian dosing-time of isoniazid (INH) in mice. A potentially toxic INH dose (120 mg/kg) was injected by i.p. route to different groups of animals at three different circadian times: 1, 9, and 17 Zeitgeber time (ZT). INH administration at 1 ZT resulted in a maximum hepatotoxicity assessed by the significant increase in both serum transaminase (ALAT: alanine aminotransferase) and (ASAT: aspartate aminotransferase) and antioxidant enzyme activities (catalase: CAT and superoxide dismutase: SOD). The highest malondialdehyde (MDA) level indicating an induction of lipid peroxidation resulting in oxidative damage was also observed at 1 ZT. Liver histopathology from INH groups at 9 ZT and at 1 ZT showed moderate to severe cytoplasma vacuolation, hepatocyte hypertrophy, ballooning, and necrosis. The circadian variation in INH toxicity may help realize a chronotherapy protocol in humans based on the selection of the best time associated to optimal tolerance or least side effects.

A novel insight on chronic AlCl3 neurotoxicity through IL-6 and GFAP expressions: Modulating effect of functional food fenugreek seeds

Abstract Objective This study was designed to review the effect of chronic aluminium exposure on interleukin-6 (IL-6) secretion in the posterior brain and test the putative modulating effect of fenugreek seeds. Methods Female Wistar rats were divided into four groups: control; AlCl3 during 5 months (500 mg/kg body weight, intragastric for 1 month then 1600 ppm via the drinking water); AlCl3 plus fenugreek seed powder (FSP) (5%) during the last 2 months and FSP alone. Results Oral administration of aluminium chloride during 5 months caused hypoproduction of IL-6 together with a decrease in GFAP reactivity and an alteration of antioxidant status in the posterior brain. On the other hand, fenugreek seeds supplementation was able to enhance IL-6 expression, re-increase GFAP reactivity, and modulate the pro-oxidant-related effect. Discussion In the context of recent researches, IL-6 hypoproduction in the posterior brain could be a novel mechanism of Al chronic toxicity with a direct effect on glial cells. Using FSP as a diet supplement could offer a neuroprotective effect against Al toxicity. This could be mediated by astroglial cells protection, antioxidant and immunomodulatory actions.

Hepatoprotective effect of Opuntia microdasys (Lehm.) Pfeiff flowers against diabetes type II induced in rats

Opuntia sp. has long been used as a folk medicine to treat hepatitis and diabetes in Sicile (Italy). To extract the polyphenols from the flower of Opuntia microdasys Lehm. at post flowring stage and evaluate the antidiabetic activity in vitro and in vivo. The hepatoprotective activity of Opuntia microdasys aqueous flowers extract at post flowering stage (OFP) has been tested for their antidiabetic activity. On fructose-alloxan induced diabete in rat model, evaluating the inhibitory effects of OFP on some carbohydrate metabolizing enzymes, pancreatic α-amylase and intestinal α-glucosidase activities in vitro. The OFP extract showed inhibitory activity against α-glucosidase (IC50=0.17±0.012mg/ml) and α-amylase (IC50=2.55±0.41mg/ml). The inhibitory potential of OFP extract on these enzymes suggests a positive and probable role of this extract in the management and treatment of diabetes mellitus, particularly, for type 2. Oral administration of the OFP at 200mg/kg to diabetic male rats for 28days demonstrated a significant protective effect by lowering the levels of glucose (123.21±1.38mg/dL) and hepatic marker enzymes (AST, ALT, LDH, γ-GT, BT, PAL, TC, LDL-C, HDL-C and TG). OFP attenuated oxidative stress by decreasing the SOD, CAT, GPX activity and the levels of PC and MDA in the liver and restored the histological architecture of the rat liver. OFP has protective effects on the protection of liver, thereby reducing some of the causes of diabetes in experimental animals.