الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
Abstract
Medicinal plants with all their parts are an integral part of global traditional medicine that are used to treat various ailments. Many pharmaceutical agents have been discovered by screening natural products from plants employed in cancer treatment. Several outstanding describing the effects of medicinal plants e.g, R. officinalis and S. lappa on complications of chemotherapy especially Cisplatin on the physiological and immunological components or indices has been investigated. Phytochemicals are natural plant-derived compounds that have been used for treating various diseases, including malignant tumors. These agents are widely available, highly tolerated, and cost-effective when compared to synthetic molecules. Therefore phytochemicals are capable of re- versing cisplatin resistance in various malignancies, with less toxic effects. Therefore, it was hypothesized that using medicinal plants, as a protective and ameliorative agent that may enhance the immune response and improve physiological functions, which impared in mice due to Ehrlich tumor inoculation. Accordingly, the objective of the present study was to investigate the improving effects of natural products of R. officinalis and S. lappa extracts, alone or combined, on complications induced by cisplatin chemotherapy in tumor bearing mice. Methodology: To achieve the above objective, ninety female Swiss albino mice were randomly divided into six groups (n=15/group). One mice group was left as a naive control and the other 5 groups were inducted with tumor cells that received cisplatin on D3 to D7 and administrated with oral medicinal plant extract in concurrent with cisplatin from D3 to D14 every other day. At the end of the treatment protocols, mice were fasted overnight, weighted and blood samples from the post-orbital plexus were collected and tissue samples were obtained after anesthetizing and dissecting mice. One part of each blood sample was used for hematological indices and the other part was centrifuged at 3000 rpm for 15 minutes to separate sera for further biochemical investigations such as liver, kidney, thyroid functions, cholesterol and triglycerides were determined by chemical methods. The activity of oxidative stress biomarkers such as superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) were also estimated. Furthermore, immunological investigations such as WBCs count and differentials, flowcytometric analysis of CD4+ and CD8+ lymphocytes sunsets. However, the results obtained from this study can be summarized in the following items. 1. The ethanolic extraction of the active ingredients in S. lapps (SLRE) was superior and highest than R. officinalis (ROLE) in the same amount (50 g) of dry powder. Additionally, the amount of yield extract in SLRE is higher than ROLE (16.894 %and 21.432 %, respectively) from initial weight 50 g. 2. The phytochemical analysis of both extracts were clearly revealed that ROLE has a potent antioxidant activity (17.38 %) than SLRE (15.26 %), while SLRE showed the strongest DPPH radical scavenging activity (32.25%) than ROLE (19.30%). Regarding total phenolic content (TPC) in both extracts, the ethanol extract of ROLE showed a high content of total phenols (156.32) than SLRE (146.06) mg GAE/g of extract. 3. Present results showed that increasing the body weight of mice inoculated with Ehrlich ascetic carcinoma cell line followed cisplatin, on contrary decreasing the relative weights of the internal organs. While when treatment using natural products such as ROLE or SLRE or in combinational form improved not only the body weight but also the relative weights of the internal organs near to the control. 4. Tumor morphology, tumor cells count and volume, showed a significant increase in the tumor cells count in EAC-bearing mice. The treatment with Cis/ROLE, Cis/SLRE, or Cis/ROLE/SLRE showed no significant changes compared to EAC/Cis (Gp3). The treatment of tumor bearing mice with Cis significantly decreased splenocytes count and the concurrent treatment with both combined plant extracts restored normal splenocytes count. 5. Regarding CBC, there was no significant change in peripheral RBCs, WBCs, and platelets counts, as well as hemoglobin content and PCV of tumor-bearing mice treated with cisplatin, or cis concomitant with orall administration of ROLE or SLRE, alone or combined were not changed significantly. Interestingly, neutrophils were highly significantly increased in EAC-bearing mice and EAC/Cis compared to prospective control mice. The percentage of neutrophils in EAC/Cis mice concomitant with either ROLE or SLRE returned neutrophils near the normal when compared to naïve group; combination of both extracts improved markedly neutrophils percentage. 6. Results of liver function tests showed that the serum enzymes and bilirubin (Direct, Indirect) levels were highly significant increased after induction of Ehrlich ascetic carcinoma. On treatment of mice with EAC/Cis/ROLE or EAC/Cis/SLRE decreased the serum activity of ALT, AST and ɣGT in addition to bilirubin level toward normal compared to EAC-mice. After treatment of EAC-mice with a combined form of EAC/Cis/ROLE/SLRE improved liver enzymes about normal compared to the control mice. 7. Results of kidney function tests showed that induction of mice with tumor cells diminished both creatinine and urea levels in their blood. There was an improvement in both creatinine and urea level in the blood due to treatment of EAC-mice with Cis, this improvement was continued after treatment with ROLE or SLRE; the combined form was marked. 8. It is obvious from obtained results that induction with tumor cells increased serum total cholesterol and triglycerides levels in mice blood and their treatment with cis led to a significant decrease. The administration of ROLE or SLRE in groups treated with cisplatin was no effective enough while treatment with a combined extracts improved serum total cholesterol and triglycerides levels, as well as cholesterol lipoproteins. Induction of EAC diminished HDL level and increased LDL and vLDL levels. On the other hand, treatment of EAC-mice with Cis followed by both extracts improved HDL level, LDL and vLDL, optimizing their values compared to prospective control mice. 9. The inoculation of mice with tumor cells decreased the serum levels of oxidant (GSH) and the anti-oxidant (SOD). In contrary, these treatments highly increased (MDA) serum level as a lipid perioxidation end product. The treatment of EAC-mice with cis gave a little improvement and both ROLE and SLRE either alone or in combination recovered the serum levels of all oxidative stress markers and organs functions. 10. The heart function tests showed that tumor induction in mice increased troponin and CPK contents in the heart tissue. Administration of cis and two herbal extracts together showed ameliorative effect for improving TN and CPK contents in the heart near to the control. 11. The obtained data showed that the induction of Ehrlich ascetic carcinoma increased the serum levels of both Free T3 and decreased the pituitary TSH. Treatment of tumorized mice with cis plus medicinal plant extracts to mice can enhance and regulate the thyroid function around normal values. 12. The obtained results herein indicated that CD4+, CD8+ T lymphocyte subsets increased significantly in most of mice groups treated with ROLE or SLRE, or in a combination, compared to EAC alone and EAC/cis. In addition, the illustrated data revealed CD4+, CD8+ T lymphocyte increased above normal values in the control indicating enhancement of the cellular immune response after administrating with plant extracts. Conclusion: it can be concluded that the current results suggest that administration of natural products such as ROLE or SLRE or a combined form to EAC-mice treated with cisplatin chemotherapy can reduce the health hazards induced by cis via exerting beneficial effects on the general physiological and immunological indices. These plant extracts can reduce body weight, its internal organs and lipid components (cholesterol and triglycerides) in the blood. Both plant extracts can normalize the involved anti-oxidative enzymes activity and increased MDA excretion and this result can enhance the cardiovascular activity and reduce fatty liver incidence. These treatments can improve the liver, kidney, heart and thyroid functions by normalizing serum liver enzyme activity, urea and creatinin indicating intact liver and kidney tissues. In opportunity, treatments have potency to enhance postoperative cellular immunity, promote cell activation and differentiation of CD4+, CD8+ T lymphocyte subsets. Recommendation: This study recommends using plant natural products, single or combined, due to their beneficial roles on reducing or imitating side effects of chemotherapy and they improve body weight, organ’s functions, and anti-lipidemic by enhancing antioxidant properties. Also they can enhance the immune health by improving CD4+, CD8+ production.