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Information Seminar Paper

Title

PROTECTIVE EFFECTS OF OXYGEN PRETREATMENT ON RENAL TUBULAR CELLS IS ASSOCIATED WITH DECREASING CYTOTOXIC EFFECTS OF CISPLATIN ON CERVICAL BUT NOT OVARIAN CANCER CELLS

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Abstract

 INTRODUCTION: WE HAVE SHOWN IN PREVIOUS IN VITRO STUDIES THAT OXYGEN PRETREATMENT LARGELY PROTECTS HUMAN EMBRYONIC RENAL TUBULAR CELL AGAINST ACUTE CISPLATIN TOXICITY. THE AIM OF PRESENT STUDY WAS TO DETERMINE WHETHER THIS BENEFICIAL EFFECT IS ASSOCIATED WITH DECREASING THERAPEUTIC EFFECTS OF CISPLATIN ON MALIGNANT CELLS OR NOT?METHODS: IN THIS IN VITRO STUDY, CULTURED HUMAN EMBRYONIC RENAL TUBULAR EPITHELIAL (AD293), CERVICAL CANCER (HELA) AND OVARIAN CANCER (OVCR-3) CELLS WERE SUBJECTED TO EITHER 2 HOURS PRETREATMENT WITH OXYGEN (³90%) OR NORMAL AIR AND THEN TO A PREVIOUSLY DETERMINED 50% LETHAL DOSE OF CISPLATIN FOR 24 HOURS. VIABILITY OF CELLS WAS DETERMINED VIA MTT AND NEUTRAL RED ASSAYS. ALSO, ACTIVATED CASPASE 3 AND BAX/BCL-2 RATIO, AS BIOCHEMICAL MARKERS OF CELL APOPTOSIS, WERE DETERMINED USING IMMUNOBLOTTING.RESULTS: OXYGEN PRETREATMENT SIGNIFICANTLY INCREASED CELL VIABILITY AND DECREASED CISPLATININDUCED APOPTOSIS BOTH IN NORMAL RENAL TUBULAR EPITHELIAL CELLS (AD293) AND CERVICAL CANCER (HELA) CELLS. THIS OXYGEN PRE-EXPOSURE METHOD DOSE NOT SIGNIFICANTLY REDUCED CYTOTOXIC EFFECTS OF CISPLATIN ON OVARIAN CANCER (OVCR-3) CELLS AS WAS DETERMINED BOTH BY CELL VIABILITY (MTT AND NEUTRAL RED) AND WESTERN-BLOT APOPTOSIS MARKERS (CASPASE 3 ACTIVATION AND BAX/BCL-2 RATIO) ASSAYS.CONCLUSION: USING SOME PROTECTIVE METHOD FOR REDUCING CISPLATIN NEPHROTOXIC SIDE EFFECTS LIKE OXYGEN PRETREATMENT MAY BE ASSOCIATED WITH SIMULTANEOUS REDUCING THERAPEUTIC CYTOTOXIC EFFECTS OF CISPLATIN ON SOME MALIGNANT CELLS LIKE CERVICAL CANCER (HELA) CELLS. IN SOME OTHER CELL LINES LIKE OVARIAN CANCER (OVCR-3) CELLS, THIS VALUABLE PROTECTIVE EFFECT OF OXYGEN PREEXPOSURE IS NOT ASSOCIATED WITH DECREASING THERAPEUTIC EFFECTS OF CISPLATIN.

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