PERFLUOROOCTANESULFONATE (PFOS) INDUCES APOPTOSIS SIGNALING AND PROTEOLYSIS IN HUMAN LYMPHOCYTES THROUGH ROS MEDIATED MITOCHONDRIAL DYSFUNCTION AND LYSOSOMAL MEMBRANE LABIALIZATION

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Zarei Mohammad Hadi; HOSSEINI SHIRAZI SEYED FARSHAD; AGHVAMI MARJAN; POURAHMAD JALAL

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Journal Paper

Paper Information

Journal: Iranian Journal of Pharmaceutical Research Year:2018 | Volume:17 | Issue:3 Page(s): 995-1007

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Title

PERFLUOROOCTANESULFONATE (PFOS) INDUCES APOPTOSIS SIGNALING AND PROTEOLYSIS IN HUMAN LYMPHOCYTES THROUGH ROS MEDIATED MITOCHONDRIAL DYSFUNCTION AND LYSOSOMAL MEMBRANE LABIALIZATION

Author(s)

Zarei Mohammad Hadi | HOSSEINI SHIRAZI SEYED FARSHAD | AGHVAMI MARJAN | POURAHMAD JALAL | Issue Writer Certificate

Keywords

PERFLUOROOCTANESULFONATE (PFOS)

REACTIVE OXYGEN SPECIES (ROS)

HUMAN LYMPHOCYTE

CELLULAR PROTEOLYSIS

LYSOSOMAL MEMBRANE INTEGRITY

CYTOTOXICITY

Abstract

Perfluorinated compounds (PFCs) such as perfluorooctanesulfonate (PFOS) are stable chemicals that accumulate in biological matrix. Toxicity of these compounds including immunotoxicity has been demonstrated in experimental models and wildlife. Although limited number of studies examined the effects of PFOS on HUMAN LYMPHOCYTEs but so far no research has investigated the complete mechanisms of PFOS CYTOTOXICITY toward HUMAN LYMPHOCYTEs. The main goal of this investigation was to find out the mechanisms underlying the cytotoxic effect of PFOS toward HUMAN LYMPHOCYTEs using accelerated CYTOTOXICITY mechanisms screening (ACMS) technique. HUMAN LYMPHOCYTEs were isolated from blood of healthy donors using Ficoll-paque PLUS standard method. Cell viability was determined following 12 h of incubation of HUMAN LYMPHOCYTEs with 100-500 μM PFOS. Our results showed that IC50 concentration (163.5 mM) of PFOS reduced viability of HUMAN LYMPHOCYTEs approximately 50% via increased ROS formation, lipid peroxidation, glutathione depletion and damage to cell sub organelles such as mitochondria and lysosomes. Besides, in this study we demonstrated involvement of CELLULAR PROTEOLYSIS and activation of caspase-3 in PFOS induced lymphocyte CYTOTOXICITY. We finally concluded that at environmentally related concentration, PFOS can induce toxic effect toward HUMAN LYMPHOCYTEs through induction of oxidative stress and damage to cell sub organelles.

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APA: Copy

Zarei, Mohammad Hadi, HOSSEINI SHIRAZI, SEYED FARSHAD, AGHVAMI, MARJAN, & POURAHMAD, JALAL. (2018). PERFLUOROOCTANESULFONATE (PFOS) INDUCES APOPTOSIS SIGNALING AND PROTEOLYSIS IN HUMAN LYMPHOCYTES THROUGH ROS MEDIATED MITOCHONDRIAL DYSFUNCTION AND LYSOSOMAL MEMBRANE LABIALIZATION. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), 17(3), 995-1007. SID. https://sid.ir/paper/288775/en

Vancouver: Copy

Zarei Mohammad Hadi, HOSSEINI SHIRAZI SEYED FARSHAD, AGHVAMI MARJAN, POURAHMAD JALAL. PERFLUOROOCTANESULFONATE (PFOS) INDUCES APOPTOSIS SIGNALING AND PROTEOLYSIS IN HUMAN LYMPHOCYTES THROUGH ROS MEDIATED MITOCHONDRIAL DYSFUNCTION AND LYSOSOMAL MEMBRANE LABIALIZATION. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR)[Internet]. 2018;17(3):995-1007. Available from: https://sid.ir/paper/288775/en

IEEE: Copy

Mohammad Hadi Zarei, SEYED FARSHAD HOSSEINI SHIRAZI, MARJAN AGHVAMI, and JALAL POURAHMAD, “PERFLUOROOCTANESULFONATE (PFOS) INDUCES APOPTOSIS SIGNALING AND PROTEOLYSIS IN HUMAN LYMPHOCYTES THROUGH ROS MEDIATED MITOCHONDRIAL DYSFUNCTION AND LYSOSOMAL MEMBRANE LABIALIZATION,” IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), vol. 17, no. 3, pp. 995–1007, 2018, [Online]. Available: https://sid.ir/paper/288775/en

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