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BackgroundCisplatin (CIS) is a potent antineoplastic agent with high therapeutic efficacy against many kinds of tumors. Its use is limited by its nephrotoxicity. The aim of this work was to minimize cisplatin effective dose and the possible reduction of its severe side effects. The present study was designed to assess the role of sulfur containing agent dimethyl sulfoxide (DMSO) on sensitization of mammary carcinoma, Ehrlich ascites carcinoma (EAC), to the action of cisplatin and at the same time the possible protective effect against cisplatin induced nephrotoxicity in experimental animals.MethodsTo evaluate these effects we have explored the cisplatin effect on the survival time of tumor-bearing animals, tumor weight, cisplatin cellular uptake, apoptosis induction and cell cycle distribution and renal function in presence and absence of DMSO.ResultsCisplatin at dose of 4.5 mg/kg increased the mean survival time of tumor bearing mice to 37 days compared with tumor bearing control mice. Pretreatment of tumor bearing mice with DMSO 50 % (2 ml/kg equal to 1 gm/kg) 2 h. before cisplatin showed a significant increase in their mean survival time 43 days compared to cisplatin treated animals. DMSO pretreatment retained rat’s serum urea and creatinine levels to normal compared to animals treated with cisplatin alone.ConclusionDMSO pretreatment enhanced the cytotoxic activity of cisplatin against the growth of EAC in vivo and showed protective effects against cisplatin-induce nephrotoxicity.

Background: Doxorubicin (DOX) is an effective antineoplastic drug indicated to treat many cancerous diseases but its clinical usefulness is limited by many side effects. The main and the most serious one is DOX induced cardiotoxicity. Many strategies have been tried to minimize this side effect such as addition of cardioprotective agent to DOX treatment protocols. Aims: The aim of this work was directed to investigate whether marine astaxanthin (ATX), a xanthophyll carotenoid pigment with potent antioxidant effect, could protect heart against the cardiotoxicity induced by DOX. Methodology: Forty Male Wister rats were divided into four equal groups and treated for one week as follow: Group I rats were treated with normal saline (2 ml/kg, x7, i.p.) and considered a control group. Group II rats were treated with ATX (40 mg/kg, x7, i.p.). Group III rats were treated with AlQahtani et al.; JPRI, 27(3): 1-11, 2019; Article no.JPRI.48804 2 normal saline (2 ml/kg, x7, i.p.) and a single dose of DOX (20 mg/kg, i.p.) at day 7. Finally, group IV rats were treated with ATX (40 mg/kg, x7, i.p) and with a single dose of DOX (20 mg/kg, i.p.) at day 7. After 24 and 48 hrs of treatment, rats were anesthetized and prepared for collection of blood samples and heart isolation. The cardioprotective effect of ATX against DOX induced cardiotoxicity were evaluated by measurement of the serum level of cardiac enzymes CPK by colorimetric assay and CK-MB by Eliza. Also the levels of serum total antioxidant capacity (TAC) were measured colorimetrically. In addition, the Malondialdehyde (MDA), reduced glutathione, glutathione peroxidase (GPx) levels and superoxide dismutase (SOD) were determined in heart tissues homogenate by colorimetric method. In addition, Heart sample were taken for histopathology studies. Results: The Addition of ATX to DOX significantly (p<0.05) decreased the serum level of cardiac enzymes (CPK, CK-MB) and increased the serum total antioxidant capacity in compare with these levels in sera of rats treated with DOX only. This addition also significantly decreased the level of malondialdehyde and increased the reduced glutathione and glutathione peroxidase and superoxide dismutase significantly in the heart tissues homogenate in compare to corresponding levels in rats treated with DOX alone. Histopathological investigation of cardiac tissues confirmed the biochemical studies, where addition of ATX to DOX treatment protocol showed that the fragmentation of the muscle fiber revealed normal with central vesicular nuclei and prevented a marked disruption of normal cardiac architecture which resulted from DOX treatment. Conclusion: Marine astaxanthin provides excellent cardioprotective effect against doxorubicin induced cardiotoxicity in rats. Original Research Article