A COMPARISON OF HEPATOCYTE CYTOTOXIC MECHANISMS FOR DOCETAXEL AND PLGA- DOCETAXEL NANOPARTICLS

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DARAEI BAHRAM; AGHVAMI MARJAN; POURAHMAD JALAL; DINARVAND RASSOUL

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Journal: Iranian Journal of Pharmaceutical Research Year:2017 | Volume:16 | Issue:1 Page(s): 249-265

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Information Journal Paper

Title

A COMPARISON OF HEPATOCYTE CYTOTOXIC MECHANISMS FOR DOCETAXEL AND PLGA- DOCETAXEL NANOPARTICLS

Author(s)

DARAEI BAHRAM | AGHVAMI MARJAN | POURAHMAD JALAL | DINARVAND RASSOUL | Issue Writer Certificate

Keywords

DOCETAXEL

POLYLACTIDE-CO-GLYCOLIDE

PLGA-DTX NANOPARTICLES

CYTOTOXICITY

RAT HEPATOCYTE

SILYMARIN

Abstract

DOCETAXEL (DTX) is one of the most widely used drugs in oncology due to its high efficacy against several cancers. Though, its routine clinical administration, formulated in tween 80, causes serious side effects. POLYLACTIDE-CO-GLYCOLIDE (PLGA), biodegradable polyester synthesized and approved for human use, is employed to overcome these problems.In this investigation, we compare the cytotoxic mechanisms of DTX and PLGA-DTX in isolated RAT HEPATOCYTEs. CYTOTOXICITY of DTX and PLGA-DTX were associated with reactive oxygen species formation, activation of caspases cascade, collapse of mitochondrial membrane potential (MMP), lysosomal membrane leakiness and ATP depletion. Our results also showed that CYP2E1 is involved in the oxidative stress CYTOTOXICITY mechanism and both drugs are detoxified via phase II metabolic methylation. Furthermore, we concluded that PLGA-DTX is bioactivated by GSH. It could also potentiate hepatocyte toxicity through a mitochondrial/ lysosomal toxic cross- talk. In addition to these observed differences, it is likely that mode of hepatocyte membrane penetration is different between these compounds.

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APA: Copy

DARAEI, BAHRAM, AGHVAMI, MARJAN, POURAHMAD, JALAL, & DINARVAND, RASSOUL. (2017). A COMPARISON OF HEPATOCYTE CYTOTOXIC MECHANISMS FOR DOCETAXEL AND PLGA- DOCETAXEL NANOPARTICLS. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), 16(1), 249-265. SID. https://sid.ir/paper/288837/en

Vancouver: Copy

DARAEI BAHRAM, AGHVAMI MARJAN, POURAHMAD JALAL, DINARVAND RASSOUL. A COMPARISON OF HEPATOCYTE CYTOTOXIC MECHANISMS FOR DOCETAXEL AND PLGA- DOCETAXEL NANOPARTICLS. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR)[Internet]. 2017;16(1):249-265. Available from: https://sid.ir/paper/288837/en

IEEE: Copy

BAHRAM DARAEI, MARJAN AGHVAMI, JALAL POURAHMAD, and RASSOUL DINARVAND, “A COMPARISON OF HEPATOCYTE CYTOTOXIC MECHANISMS FOR DOCETAXEL AND PLGA- DOCETAXEL NANOPARTICLS,” IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), vol. 16, no. 1, pp. 249–265, 2017, [Online]. Available: https://sid.ir/paper/288837/en

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