الفهرس 
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Abstract
The modem chemotherapy of cancers, which mainly refers to genotoxic/cytotoxic drugs, started around 1940s and has developed into several types, including alkylating agents, anthracyclines, plant alkaloids, topoisomerase inhibitors, and antimetabolites. Most of the above chemotherapeutic drugs inhibit tumor growth by causing DNA damages, arresting DNA replication, and cell division. Unfortunately, the dosage and treatment duration of these drugs, which are essential for maximizing their antitumor effects, are often limited due to severe toxicities to normal tissues.
Carboplatin, a platinum-containing anticancer dmg, is currently being used against a variety of cancers. However, a single high dose of carboplatin is ototoxic in cancer patients. The antioxidant enzyme activities such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase (GST) depressed significantly at higher doses of carboplatin. Thalidomide is a teratogen with anti-angiogenic properties and causes stunted limb growth (dysmelia) during human embryogenesis. Thalidomide exerts its anti- angiogenic properties via the generation of toxic hydroxyl radicals, which impair vasculogenesis and angiogenesis during embryonic body development. One of the main mechanisms of chemotherapy drugs against cancer cells is the formation of reactive oxygen species (ROS), or free radicals.
Antioxidants such as vitamin E, vitamin C, folic acid, isoflavones, quercetin, curcumin, ginger and grape seed proanthocyanidin extract (GSPE) can protect against the effects of oxygen species. Oligomeric proanthocyanidins, naturally occurring antioxidants widely available in fruits, vegetables, nuts, seeds, flowers and bark, have been reported to possess a broad spectrum of biological, pharmacological and therapeutic activities against free radicals and oxidative stress
Therefore, the present study was conducted to determine nephrotoxicity and neurotoxicity by thalidomide followed by carboplatin via oxidative damage, tumor suppressor gene P53 (P53), tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6) and histopathological changes in male rats. Also, investigate the chemo-protective effects of GSPE.
In the present study Wistar male rats were used. Animals were divided into 4 equal groups as follows: group 1 was used as control, group 2 was treated with GSPE (200 mg/kg BW) alone, group 3 was treated with thalidomide (60 mg/kg BW) for 14 days followed by carboplatin (196 mg/kg BW) for 14 days, and group 4 was treated with combination of GSPE and thalidomide for 14 days followed by GSPE and carboplatin for 14 days.
The obtained results can be summarized as follow:-
1- The data showed that treatment with GSPE alone reduced the levels of TBARS and NO in kidney and brain, while treatment with thalidomide and carboplatin significantly increased their levels in tested organs. GSPE alone significantly increased TAC, GSH and antioxidant enzymes (SOD, CAT, GPx and GST), but thalidomide and carboplatin significantly.