Cisplatin is widely used chemotherapeutic agent for cancer treatment with limited uses due to its neurotoxic side effect. The aim of this study was to determine the potential preventive effects of rutin on the brain of cisplatin- neurotoxic rat model. Forty rats were divided into four groups. Group-1 (control group) was intra-peritoneal (IP) injected with 2.5 ml/kg saline. Group-2 (rutin group) was orally administrated 30 mg/kg rutin dissolved in water for 14 days. Group-3 (cisplatin group) was IP received 5 mg/kg cisplatin single dose. Group-4 (rutin and cisplatin group) was orally administrated 30 mg/kg rutin dissolved in water for 14 days with a single dose of 5 mg/kg cisplatin IP on day ten. Brain tissues from frontal cortex was used to extract RNA, the gene expression levels of paraoxonase-1 (PON-1), PON-2, PON-3, peroxisome proliferator-activated receptor delta (PPAR-δ), and glutathione peroxidase (GPx) was investigated by Real-time PCR. Cisplatin significantly decreased the expression levels of PON-1, PON-3, PPAR-δ and GPX whereas significantly increased PON-2 expression levels. Co-administration of Rutin prevented the cisplatin-induced toxicity by restoring the alteration in the studied genes to normal values as in the control group. This study showed that Rutin has neuroprotective effect and reduces cisplatin- neurotoxicity with possible mechanism via the antioxidant pathway.

Background: Breast cancer is affected by the immune system in that different cytokines play roles in its initiationand progression. Interleukin-10 (IL-10), an anti-inflammatory cytokine, is an immunosuppressive factor involved intumorigenesis. The present study was conducted to investigate the gene silencing effect of a small interference RNA(siRNA) targeting IL-10 on the apoptotic pathway in breast cancer cell line. Methods: The siRNA targeting IL-10 anda glyceraldehyde 3-phosphate dehydrogenase (GAPDH) clone were introduced into MDA-MB-231 cells. Real-timePCR assays were used to determine IL-10 and GAPDH gene expression levels, in addition to those for protein kinaseB (AKT), phosphoinositide 3-kinase (PI3K), B-cell lymphoma 2 (Bcl2), caspase-3 and caspase-9 genes related toapoptosis. Results: Inhibition of IL-10 by the siRNA accelerated apoptosis and was accompanied by significantincrease in caspase-3 and caspase-9 and a significant decrease in PI3K, AKT and Bcl2 expression levels compared tothe non-transfected case. Conclusions: In conclusion, the production of IL-10 may represent a new escape mechanismby breast cancer cells to evade destruction by the immune system. IL-10 gene silencing causes down regulation of bothPI3K/AKT and Bcl2 gene expression and also increases the Bbc3, BAX caspase3, and caspase 3 cleavage expressionlevels. IL–10 might represent a promising new target for therapeutic strategies.