Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Rue Avicenne, 5019, Monastir, Tunisia.
BMC Complement Altern Med. 2012 Jul 31;12:111. doi: 10.1186/1472-6882-12-111.
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.
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.
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.
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.
顺铂（cis-Platinum (II)）（顺式二氨二氯铂；CDDP）是一种广泛用于治疗多种恶性肿瘤的有效抗肿瘤化合物。CDDP 的一个重要副作用是肾毒性。这种药物的细胞毒性作用通常被认为会诱导氧化应激，并与其结合 DNA 形成 CDDP-DNA 加合物和肾细胞凋亡的能力有关。在这项研究中，我们研究了仙人掌茎提取物（CCE）对 CDDP 诱导的氧化应激和遗传毒性的保护作用。我们还观察了丙二醛（MDA）、过氧化氢酶活性、超氧化物歧化酶（SOD）活性、染色体畸变（CA）试验、SOS 显色试验、肾中 p53、bax 和 bcl2 的表达水平，以及血清生化分析等几种肾功能标志物毒性参数。
成年、健康的 balb/c（20-25 g）雄性小鼠，4-5 周龄，经腹腔注射 CCE（50 mg/Kg.b.w）预处理 2 周。对照组动物每周 3 天腹腔注射 100 μg/Kg.b.w CDDP 4 周。用 CDDP 和 CCE 处理的动物分为两组：第一组在每周 3 天用 CDDP 处理前 2 小时给予 CCE，连续 4 周。第二组未用 CCE 预处理，但在每周 3 天用 CDDP 处理后 24 小时给予该提取物，连续 4 周。
我们的结果表明，CDDP 诱导了所有测试的氧化应激标志物的显著改变。此外，它还诱导了骨髓细胞中的 CA，增加了促凋亡蛋白 p53 和 bax 的表达，降低了肾中抗凋亡蛋白 bcl2 的表达。另一方面，CDDP 显著增加了尿素和肌酐的水平，降低了白蛋白和总蛋白的水平。CCE 无论是在 CDDP 处理前还是处理后进行治疗，都显示出（i）对所有测试标志物的 CDDP 诱导的氧化损伤的全面减少，（ii）抗遗传毒性作用，从而有效地防止了与单独用 CDDP 处理的组相比的染色体畸变（iii）通过差异调节 p53 的表达来限制 CDDP 的作用，p53 及其相关基因如 bax 和 bcl2 均降低，（iv）限制血清肌酐、尿素、白蛋白和总蛋白的水平，使其值恢复到接近对照的正常水平。
我们得出结论，CCE 通过其抗氧化、抗遗传毒性和抗凋亡特性，对 CDDP 诱导的小鼠肾功能障碍有益。
