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

BMC Complementary and Alternative Medicine

Hassen Bacha²  Lazhar Zourgui⁵  Hedi Ben Mansour³  Chayma Bouaziz⁴  Mbarka Hfaiedh¹  Yousra Ayed⁴  Dalel Brahmi¹ 

[1]Research unit of Macromolecular Biochemistry & Genetic, Faculty of Sciences Gafsa, Gafsa, 2112, Tunisia

[2]University of Jendouba, Jendouba, Tunisia

[3]Laboratory of Cellular and Molecular Biology, Faculty of Dental Medicine, University of Monastir, Rue Avicenne, Monastir, 5000, Tunisia

[4]Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Rue Avicenne, 5019, Monastir, Tunisia

[5]Higher Institute of Applied Biology ISBAM Medenine, University of Gabes, Gabes, Tunisia

关键词: Protective effect;    Antioxidant;    Genotoxicity;    CDDP;    Cactus;   

Others  :  1232104
DOI  :  10.1186/1472-6882-12-111

 received in 2011-08-18, accepted in 2012-06-21,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Brahmi et al.; licensee BioMed Central Ltd.

【 图 表 】

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