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author:("Bacha, hassan")
1.  Protective effect of cactus cladode extract against cisplatin induced oxidative stress, genotoxicity and apoptosis in balb/c mice: combination with phytochemical composition 
Background
Cis-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.
Methods
Adult, 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.
Results
Our 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.
Conclusion
We concluded that CCE is beneficial in CDDP-induced kidney dysfunction in mice via its anti-oxidant anti-genotoxic and anti-apoptotic properties against CDDP.
doi:10.1186/1472-6882-12-111
PMCID: PMC3567432  PMID: 22849573
Cactus; CDDP; Genotoxicity; Antioxidant; Protective effect
2.  Impairment of the cell-to-matrix adhesion and cytotoxicity induced by the Mediterranean jellyfish Pelagia noctiluca venom and its fractions in cultured glioblastoma cells 
Background
The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited source of new active substances in the field of the development of bioactive products. In our study, we have investigated the efficiency of the venom from the Mediterranean jellyfish, Pelagia noctiluca and its fractions for anti-proliferative and anti-cell adhesion to cell–extracellular matrix activities.
Results
Our experiments have indicated that the separation of the Mediterranean jellyfish Pelagia noctiluca crude venom extract by sephadex G-75 chromatography led to four fractions (F1, F2, F3, and F4). Among the four fractions F1 and F3 were cytotoxic against U87 cells with IC50 values of 125 and 179 μg/ml respectively. The venom, F1, F2 and F 3 showed significant anti-proliferative activity in time-dependent manner. Our results also suggest that these fractions and the venom are able to inhibit cell adhesion to fibrinogen in dose-dependent manner. This inhibition is reliant on its ability to interact with integrins.
Conclusions
To conclude, we have demonstrated for the first time that Pelagia noctiluca venom and its fractions especially (F1 and F2) display potent anti-tumoral properties. Separation by sephadex G-75 chromatography give rise to more active fractions than the crude venom extract. The purification and the determination of chemical structures of compounds of these active fractions are under investigation. Overall, Pelagia noctiluca venom may has the potential to serve as a template for future anticancer-drug development.
doi:10.1186/1476-511X-11-84
PMCID: PMC3537653  PMID: 22741917
Pelagia noctiluca; Venom; Sephadex G-75; Cell proliferation; Cell adhesion
3.  Analgesic and antibutyrylcholinestrasic activities of the venom prepared from the Mediterranean jellyfish Pelagia noctiluca (Forsskal, 1775) 
Background
Toxins 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.
Methods
Sephadex 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.
Results
The 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.
Conclusions
Based 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.
doi:10.1186/1476-0711-11-15
PMCID: PMC3483011  PMID: 22691546
Pelagia noctiluca; Venom; Jellyfish; Analgesic activity; Anti-Butyrylcholinesterasic activity
4.  Induction of cytotoxicity of Pelagia noctiluca venom causes reactive oxygen species generation, lipid peroxydation induction and DNA damage in human colon cancer cells 
Background
The long-lasting and abundant blooming of Pelagia noctiluca in Tunisian coastal waters compromises both touristic and fishing activities and causes substantial economic losses. Determining their molecular mode of action is, important in order to limit or prevent the subsequent damages. Thus, the aim of the present study was to investigate the propensity of Pelagia noctiluca venom to cause oxidative damage in HCT 116 cells and its associated genotoxic effects.
Results
Our results indicated an overproduction of ROS, an induction of catalase activity and an increase of MDA generation. We looked for DNA fragmentation by means of the comet assay. Results indicated that venom of Pelagia noctiluca induced DNA fragmentation. SDS-PAGE analysis of Pelagia noctiluca venom revealed at least 15 protein bands of molecular weights ranging from 4 to 120 kDa.
Conclusion
Oxidative damage may be an initiating event and contributes, in part, to the mechanism of toxicity of Pelagia noctiluca venom.
doi:10.1186/1476-511X-10-232
PMCID: PMC3254669  PMID: 22151830
Pelagia noctiluca; Jellyfish; Venom; Cytotoxicity; Oxidative stress; DNA fragmentation
5.  Chemopreventive effect of cactus Opuntia ficus indica on oxidative stress and genotoxicity of aflatoxin B1 
Background
Aflatoxin 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.
Methods
Adult, 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.
Results
Our 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.
Conclusion
We concluded that CCE might have a hepatoprotective effect against aflatoxicosis in mice, probably acting by promoting the antioxidant defence systems.
doi:10.1186/1743-7075-8-73
PMCID: PMC3214131  PMID: 22008149
Cactus; Aflatoxin B1; Oxidative Stress; Genotoxicity; Hepatopretective
6.  How Much Should We Involve Genetic and Environmental Factors in the Risk Assessment of Mycotoxins in Humans? 
Despite consented efforts in prevention, mycotoxins remain a problem of human health concern in several parts of the world including developed countries. Within the same range of toxins concentrations in the blood some people develop a disease while others do not. Could this inequality in front of mycotoxins effects be explained by environment factors and/or genetic predisposition? Among recent advances in environmental health research Correlation between chronic diseases and mycotoxins in humans deserves attention through several questions: Are genetic factors involved in disease causation of mycotoxins? How much are these factors currently taken into account for mycotoxins risk assessment and how much should we involve them? Answers are still to come. Genetic and environment factors deserve therefore more attention when dealing with regulatory limits, since among the general population, those who are at risk and will develop specific diseases are likely those bearing genetic predispositions. We have addressed these questions for the specific case of ochratoxin A in humans by investigating in Tunisia, county of Jelma, in four rural families forming a household of 21 persons all exposed to ochratoxin A in diet. Our results confirm that ochratoxin A induces chronic tubular nephropathy in humans and mainly point at those having the HLA haplotype A3, B27/35, DR7 to be more sensitive to the disease for quantitatively similar or lower exposure. Persons with such haplotype were found to bear chronic interstitial nephropathy with tubular karyomegalic cells while others were apparently healthy. Godin et al. (1996) in France have also found in sibling (a sister and her brother from urban area) that have similar HLA haplotype B35-patern, OTA-related renal tubulopathy with mild proteinuria including β2-microglobulinuria. Several mechanisms are discussed that could be put ahead to explain how the HLA haplotype could lead to tubular cells lyses and renal failure. In the mean time it is urgent to search for mass screening biomarkers for mycotoxins in humans and related genetic factors to set-up more appropriate regulation.
PMCID: PMC3814714  PMID: 16705817
Mycotoxins in humans; environment and genetic factors; ochratoxin A; HLA haplotype A3; B27/35

Results 1-6 (6)