Abstract
BackgroundCisplatin (CIS) is one of the most effective anticancer drug used in the treatment of several solid tumors .Its use is limited by its nephrotoxicity. The present study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of mammary carcinoma (Ehrlich ascites carcinoma) to the action of CIS and the possible protective effect against CIS-induced nephrotoxicity in rats.MethodsThe percent survival of female tumor bearing mice was used for determination the cytotoxic activity of CIS in the presence or the absence of RSVL. Uptake and cell cycle effect, serum creatinine (CREA), blood urea nitrogen (BUN), Reduced Glutathione (GSH) and histopatholgical examination of kidney tissues after CIS and/or RSVL therapy were also investigated.ResultsRSVL increased the intracellular level of CIS in EAC cells and there was a strong correlation between the high cellular level of CIS and its cytotoxicity. CIS at a dose level of 5 mg/kg increased the mean survival time of female tumor bearing mice to 25 days compared with 17 days for tumor-bearing control mice. Administration of RSVL at a dose level of 25 mg/kg simultaneously with CIS increased the mean survival time to 48 days with 60% survival of the tumor-bearing animals. Cell cycle analysis of tumor cells showed that CIS treatment decreases the proliferation index of tumor cells while in presence of RSVL there was more significant inhibitions. Also, CIS treatment caused increase in level of creatinine and blood urea with significant decrease in the GSH level. While, in the presence of RSVL, level of creatinine and blood urea restored to control level.ConclusionThis study suggests that RSVL could increase the cytotoxic activity of CIS and protect against its nephrotoxicity.
Highlights
Cisplatin is commonly used cytotoxic drug in the management of several human solid tumors such as neck and head, testis, ovary, bladder, colorectal and breast cancers
CIS level in tumor cells Figure 2 show the cellular level of CIS in Ehrlich ascites cells after a single dose of CIS (7.5 mg/kg,i.p.) and/or RSVL (25 mg/kg,i.p.)
All the time point tested showed that simultaneous RSVL treatment significantly increased the cellular uptake of CIS in the tumor cells with maximum level 24 hours after treatment
Summary
Cisplatin is commonly used cytotoxic drug in the management of several human solid tumors such as neck and head, testis, ovary, bladder, colorectal and breast cancers. Osman et al Cancer Cell International (2015) 15:6 examining CIS antitumor activity and cell cycle distribution. Examining the possible renal protective effect of RSVL against CIS triggered nephrotoxicity. Cisplatin (CIS) is one of the most effective anticancer drug used in the treatment of several solid tumors .Its use is limited by its nephrotoxicity. The present study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of mammary carcinoma (Ehrlich ascites carcinoma) to the action of CIS and the possible protective effect against CIS-induced nephrotoxicity in rats
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
