Hedi Ben Mansour

Chemopreventive effect of cactus Opuntia ficus indica on oxidative stress and genotoxicity of aflatoxin B1

BackgroundAflatoxin B1 (AFB1) is potent hepatotoxic and hepatocarcinogenic agent. In aflatoxicosis, oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage. The aim of this work was to evaluate the hepatoprotective effect of cactus cladode extract (CCE) on aflatoxin B1-induced liver damage in mice by measuring malondialdehyde (MDA) level, the protein carbonyls generation and the heat shock proteins Hsp 70 and Hsp 27 expressions in liver. We also looked for an eventual protective effect against AFB1-induced genotoxicity as determined by chromosome aberrations test, SOS Chromotest and DNA fragmentation assay. We further evaluated the modulation of p53, bax and bcl2 protein expressions in liver.MethodsAdult, healthy balbC (20-25 g) male mice were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w) for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 250 μg/Kg.b.w AFB1. Animals treated by AFB1 and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with AFB1 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with AFB1 3 days a week for 4 weeks.ResultsOur results clearly showed that AFB1 induced significant alterations in oxidative stress markers. In addition, it has a genotoxic potential and it increased the expression of pro apoptotic proteins p53 and bax and decreased the expression of bcl2. The treatment of CCE before or after treatment with AFB1, showed (i) a total reduction of AFB1 induced oxidative damage markers, (ii) an anti-genotoxic effect resulting in an efficient prevention of chromosomal aberrations and DNA fragmentation compared to the group treated with AFB1 alone (iii) restriction of the effect of AFB1 by differential modulation of the expression of p53 which decreased as well as its associated genes such as bax and bcl2.ConclusionWe concluded that CCE might have a hepatoprotective effect against aflatoxicosis in mice, probably acting by promoting the antioxidant defence systems.

Screening of antimutagenicity via antioxidant activity in different extracts from the leaves of Acacia salicina from the center of Tunisia.

The effect of extracts obtained from Acacia salicina on genotoxicity and SOS response induced by Benzo(a)pyrene (B[a]P) as well as nifuroxazide was investigated in a bacterial assay system, i.e., the SOS chromotest with Escherichia coli PQ37. Preparations obtained from the leaves of A. salicina exhibited no genotoxicity either with or without the external S9 activation mixture. However, all extracts significantly decreased the genotoxicity induced by (B[a]P) and nifuroxazide. Ethyl acetate, methanol and TOF extracts exhibited the highest inhibition level of the SOS response induced by the direct mutagen nifuroxazide. Whereas, aqueous, ethyl acetate and methanol extracts displayed the greatest level of protection towards the indirect mutagen, (B[a]P), induced response. In addition to their antigenotoxic activity, TOF, aqueous, methanol and chloroform extracts showed an important free radical scavenging activity towards the 1,1-diphenyl 2-picrylhydrazyl (DPPH) free radical. These extracts showed IC(50) value of 36, 73, 65, and 87μg/ml respectively. Taken together, our finding showed that A. salicina exhibits significant antioxidant and antigenotoxic activities.

Protective effect of cactus cladode extract against cisplatin induced oxidative stress, genotoxicity and apoptosis in balb/c mice: combination with phytochemical composition

BackgroundCis-Platinum (II) (cis-diammine dichloroplatinum; CDDP) is a potent antitumor compound widely used for the treatment of many malignancies. An important side-effect of CDDP is nephrotoxicity. The cytotoxic action of this drug is often thought to induce oxidative stress and be associated with its ability to bind DNA to form CDDP–DNA adducts and apoptosis in kidney cells. In this study, the protective effect of cactus cladode extract (CCE) against CDDP-induced oxidative stress and genotoxicity were investigated in mice. We also looked for levels of malondialdehyde (MDA), catalase activity, superoxide dismutase (SOD) activity, chromosome aberrations (CA) test, SOS Chromotest, expressions of p53, bax and bcl2 in kidney and we also analyzed several parameters of renal function markers toxicity such as serum biochemical analysis.MethodsAdult, healthy balb/c (20–25 g) male mice aged of 4–5 weeks were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w) for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 100 μg/Kg.b.w CDDP. Animals which treated by CDDP and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with CDDP 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with CDDP 3 days a week for 4 weeks.ResultsOur results showed that CDDP induced significant alterations in all tested oxidative stress markers. In addition it induced CA in bone morrow cells, increased the expression of pro-apoptotic proteins p53 and bax and decreased the expression of anti-apoptotic protein bcl2 in kidney. On the other hand, CDDP significantly increased the levels of urea and creatinine and decreased the levels of albumin and total protein.The treatment of CCE before or after treatment with CDDP showed, (i) a total reduction of CDDP induced oxidative damage for all tested markers, (ii) an anti-genotoxic effect resulting in an efficient prevention of chromosomal aberrations compared to the group treated with CDDP alone (iii) restriction of the effect of CDDP by differential modulation of the expression of p53 which is decreased as well as its associated genes such as bax and bcl2, (iiii) restriction of serums levels of creatinine, urea, albumin and total protein resuming its values towards near normal levels of control.ConclusionWe concluded that CCE is beneficial in CDDP-induced kidney dysfunction in mice via its anti-oxidant anti-genotoxic and anti-apoptotic properties against CDDP.

Analgesic and antibutyrylcholinestrasic activities of the venom prepared from the Mediterranean jellyfish Pelagia noctiluca (Forsskal, 1775)

BackgroundToxins derived from jellyfishes have been exploited as a model for the development of new drug promising applications to treat neurodegenerative diseases. The present work is aimed to evaluate the acute toxicity of crude venom of Pelagia noctiluca and then to screen the analgesic and antibutyrylcholinestrasic (anti-BuChE) activities of the crude venom and its fractions.MethodsSephadex G75 gel was used to separate crude venom of Pelagia noctiluca, which led to some fractions. In addition, in vivo analgesic and in vitro plasma antibutyrylcholinestrasic activities were carried out with Pelagia crude venom and its fractions respectively.ResultsThe crude venom and its fractions displayed analgesic and anti-BuChE activities at different doses without inducing acute toxicity. Fraction 2 possesses the highest analgesic and antibutyrylcholinestrasic properties. The crude venom and fraction 1 had shown to possess less significant inhibitory activity against analgesic and antibutyrylcholinestrasic models.ConclusionsBased on this study, the crude venom of Pelagia noctiluca is found to be a useful tool for probing pharmacological activity. The purification and the determination of chemical structures of compounds of active fractions of the venom are under investigation.

Genotoxic and antibutyrylcholinesterasic activities of acid violet 7 and its biodegradation products

Acid violet 7, a sulfonated azo dye was degraded by Pseudomonas putida mt-2 in mineral medium at concentrations up to 200 mg/L. The genotoxicity of AV7 and its biodegradation extracts was evaluated by using the DNA-strand scission assay. No genotoxicity was observed, even with or without exposition to UV irradiation, for biodegradation under shaking conditions, but increased significantly after biodegradation under static conditions. In addition, the ability of tested compounds to reduce human plasma butyrylcholinesterase (BuChE) activity was evaluated in vitro. Genotoxicity and anti-BuChE activity generated by the azoreduction products [4′-aminoacetanilid (4′-AA) and 5-acetamido-2-amino-1-hydroxy-3,6-naphtalene disulfonic acid (5-ANDS)] were assessed and compared with that of the parent unsubstituted amines. 4′-AA exhibited a strong genotoxicity, which was imputed to the presence of the acetoxy (COCH3) substituent on the aromatic amine; however, the presence of sulphonic groups in 5-ANDS seems to be responsible for its BuChE inhibition activity. The present study demonstrates that P. putida mt-2, incubated under aerobic conditions, has a catabolism that enables it to degrade AV7 and, especially, to detoxify the dye mixtures.

Screening of antimutagenicity via antioxidant activity in different extracts from the flowers of Phlomis crinita Cav. ssp mauritanica munby from the center of Tunisia

For centuries, plants have been used in traditional medicines, and there has been recent interest in the chemopreventive properties of compounds derived from plants. In the present study, we investigated the free-radical–scavenging, antioxidant, and antimutagenic potential of polar extracts from Phlomis crinita Cav. flowers. Ethyl acetate, chloroform, and methanol extracts were prepared from powdered Phlomis flowers and characterized for the presence of tannins, flavonoids, iridoids, sterols, cardiac glycosides, and anthraquinones. All the extracts showed increased activity in scavenging the ABTS free radical, but only ethyl acetate and methanol extracts were active in scavenging the superoxide anion generated by the xanthine/xanthine oxidase system. In addition, all the extracts significantly decreased the mutagenicity induced by 2-aminoanthracene in the presence of a metabolizing homogenate (S9) and methyl methane sulfonate in the absence of metabolizing system, using the Ames test with Salmonella typhimurium TA102 and TA104. The present study indicates that extracts of P. crinita flowers are a significant source of compounds with antigenotoxic and antioxidant activity (most likely phenolic compounds) and thus may be useful candidates for chemoprevention studies.

Phytochemical, antibacterial, antiproliferative, and antioxidant potentials and DNA damage-protecting activity of Acacia salicina extracts.

The extract enriched in total oligomer flavonoids (TOF), and the aqueous, methanol, and ethyl acetate extracts of Acacia salicina were investigated for their polyphenolic compound content, antioxidative activity in the nitro blue tetrazolium/riboflavin assay system, antibacterial activity against Gram-positive and Gram-negative bacterial reference strains, antigenotoxic activity tested with the Ames assay, and cytotoxic activity against the K562 human chronic myelogenous leukemia cell line and L1210 leukemia murine cells. TOF extract was effective at inhibiting nitro blue tetrazolium reduction by superoxide radical in a nonenzymatic O(2)(*-)-generating system. Significant activity against bacterial reference strains Staphylococcus aureus, Enterococcus faecalis, Salmonella enteritidis, and Salmonella typhimurium was shown with all the tested extracts. These extracts significantly decreased the genotoxicity induced by sodium azide and 4-nitro-o-phenylenediamine. A pronounced cytotoxic effect on both leukemia cell lines was detected in TOF, methanolic and ethyl acetate extracts. The antioxidant, antimicrobial, antigenotoxic, and cytotoxic activities exhibited by A. salicina depended on the chemical composition of the tested extracts.

Isolation and characterization of antibiotic-resistant bacteria from pharmaceutical industrial wastewaters.

Contamination of surface waters in underdeveloped countries is a great concern. Treated and untreated wastewaters have been discharged into rivers and streams, leading to possible waterborne infection outbreaks which may represent a significant dissemination mechanism of antibiotic resistance genes among pathogenic bacterial populations. The present study aims to determine the multi-drug resistance patterns among isolated and identified bacterial strains in a pharmaceutical wastewater effluent in north Tunisia. Fourteen isolates were obtained and seven of them were identified. These isolates belong to different genera namely, Pseudomonas, Acinetobacter, Exiguobacterium, Delftia and Morganella. Susceptibility patterns of these isolates were studied toward commonly used antibiotics in Tunisia. All the identified isolates were found to have 100% susceptibility against colistin sulfate and 100% resistance against amoxicillin. Among the 11 antibiotics tested, six patterns of multi-drug resistance were obtained. The potential of the examined wastewater effluent in spreading multi-drug resistance and the associated public health implications are discussed.

Bioremediation of industrial pharmaceutical drugs.

Recently, attention has been drawn toward the occurrence of pharmaceuticals in the environment. In recent years, many reports have been made on the occurrence of the large, differentiated group of pharmaceuticals in wastewater (PW), surface water, ground water, and in soil. The pharmaceutical sector is currently expanding in Tunisia, with more than 34 industries. The aim of this work was to evaluate the ability of Pseudomonas putida mt-2 to treat PW. P. putida was very efficient in reducing chemical oxygen demand (COD), total dissolved solids (TDS), and turbidity of solution (85.5, 89.1, and 81.5%, respectively). Genotoxicity of effluent, before and after biodegradation, was evaluated in vivo in mouse bone marrow by assessing the percentage of cells bearing different chromosome aberrations. Results indicated that PW showed a significant ability to induce DNA damage. In addition, PW induced a remarkable lipid peroxidation (LPO) effect, however, activities of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were unchanged when treated with PW, compared to nontreated PW. This toxicity was imputed to the presence of pharmaceutical compounds in wastewater. However, chromosome aberration, as well as LPO of PW, were significantly reduced after bioremediation. Thus, the use of this strain for testing on the industrial scale seems possible and advantageous.

Toxicities effects of pharmaceutical, olive mill and textile wastewaters before and after degradation by Pseudomonas putida mt-2

BackgroundRemoval of numerous classes of chemical pollutants from the industrial wastewater such as textile, pharmaceutical and olive mill using conventional wastewater treatment, is incomplete and several studies suggested that improvement of this situation would require the application of biological treatment techniques. Dyes, polyphenols and drugs are an environmental pollutants extremely toxics to plants and other living organisms including humans. These effluents were previously treated by Pseudomonas putida. The main of this work was to evaluate the in vivo toxicity of the three wastewaters.MethodsWrithes and convulsant effect of effluents were carried out and were compared to the treated effluents. Only pharmaceutical wastewater was exhibited a convulsant effect which observed in mice treated by effluent. On the other hand, all industrial wastewater induced significantly an algogenic effects particularly when mice were treated by the pharmaceutical wastewater (Number of writhes = 44).ConclusionToxicity was totally removed when mice were treated by the bio remediated effluent. This indicates that P. putida was able to completely detoxify the toxic industrial effluent.