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The effects of chloramphenicol on mitochondrial functions Mahidol Uinversity wisdom of the land

Bone marrow

Faculty of Veterinary Science Research Seminar

Mitochondria

Nattapol Seehawat, Warapan Toniti

Chloramphenicol 3D structure


Introduction Mitochondria

•Organelle of eukaryotic cells •Power house of cell

Endosymbiosis theory

• Mitochondrial evolution • Antibiotic

Chlorammarrow phenicol • Bone suppression The effects of chloramphenicol on mitochondrial functions iStockphoto/Sebastian Kaulitzki


"Life did not take over the globe by combat, but by networking" Dr. Lynn Margulis


Endosymbiosis theory Hypothesis describing the origin of eukaryotic cell.

Gray et al., 1999


Endosymbiosis theory Genome consequence Rickettsia spp. Anaplasma spp. Ehrlichia spp. Kyriakouli et al., 2008

Gray et al., 1999


Mitochondria Structure Outer mitochondrial membrane •Phospholipid bilayer Inner mitochondrial membrane Cristae •Respiratory chain •Cardiolipin Intermembrane space •Apoptisis pathway Matrix •mtDNA


Mitochondria Function Mediation of intermediary metabolism •Heme biosynthesis Provision of ATP •Oxidative phosphorylation Initiation of apoptosis •Cytochrome-c Production of heat Contribution to heredity •mtDNA •Heteroplasmy

Wallace, 2008


Chloramphenicol Antibiotic produced by Streptomyces

venezuelae

First isolated in 1947, but now produced synthetically Bacteriostatic, broad-spectrum

Binds to 50S ribosomal subunit U.S. National Library of Medicine

Inhibit peptidyl transferase activity Trakanrungsie, 2009


The effects of chloramphenicol on mitochondrial functions Dose dependent

Myeloid cell series and Erythroid Administration of chloramphenicol Therapeutic dose

Mitochondrial stress

Protein translation Heme synthesis  or ↓Cell proliferation and differentiation

↓ATP production Smith et al., 1970


Administration of chloramphenicol Leukemia Therapeutic dose

Mouse T-cell Mitochondrial stress ď –Apoptosis Abnormal cell differentiation Yuan and Shi, 2008

Leukemia


Carcinogenic

Chloramphenicol Carcinogen 2A (Probable human carcinogen)


Mitochondrial stress Bone marrow Matrix condense ď Ş Control ď Ť Treatment with chloramphenicol 5 days

Smith et al., 1970


Dose independent Administration of chloramphenicol Therapeutic dose

Chloramphenicol metabolites

Nitroso-chloramphenicol and Hydroxyl-amino-chloramphenicol

Cytotoxic activity Damage hemopoietic stem cells Aplastic anemia Yunis et al., 1980; Kasten, 1999


‌for your attention.


ระดับ 1 เกิดมะเร็งในมนุษยไดอยางแนนอน (Known human carcinogen) ระดับ 2A มีความเปนไปไดสูงในการกอใหเกิดมะเร็งในมนุษย (Probable human carcinogen) ระดับ 2B มีความเปนไปไดในการกอใหเกิดมะเร็งในมนุษย (Possible human carcinogen) ระดับ 3 ไมจัดเปนสารกอมะเร็งในมนุษย (Not classifiable for human carcinogenicity) ระดับ 4 มีความเปนไปไดสูงที่จะไมกอใหเกิดมะเร็งในมนุษย (Probably not carcinogenic to humans)]

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