Effect of oral coadministration of artesunate with ferrous sulfate on rat liver mitochondrial membrane permeability transition.

Abstract

The recent resurgence of interest in the study of mitochondria has been fuelled in large part by the recognition that genetic and/or metabolic alterations in this organelle are causative or contributing factors in a variety of human diseases including cancer. This study hypothesizes that co-administration of artesunate and ferrous sulfate could induce apoptosis which can be targeted on cancerous cells in such a manner, thus providing a novel, viable and perhaps inexpensive way of dealing with the cancer scourge. Artesunate and Ferrous sulfate were co-administered to rats at various doses for seven days. At the end of the treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Low ionic strength mitochondria were isolated from hepatic cells of the rats and assayed for protein content; changes in the absorbance of the liver mitochondria; and mitochondrial swelling. Co-administration of artesunate and ferrous sulfate resulted in a significant increase (P<0.05) in pore opening. The difference in pore opening was found to be statistically significant (P<0.05) when the artesunate and ferrous iron-treated groups were compared with the artesunate only treated group. Results from this study show that co-administration of artesunate and ferrous sulfate can cause an opening in the mitochondrial membrane transition pore. A combined dose of ferrous sulfate and artesunate may prove to be a more potent therapy for targeting cancerous cells.

• Authors: Mosebolatan V Fafowora, Francis Atanu, Olayinka Sanya, Olufunso O Olorunsogo, Ochuko L Erukainure
• Journal: Drug and chemical toxicology (Drug Chem Toxicol) Vol. 34 Issue 3 Pg. 318-23 (Jul 2011) ISSN: 1525-6014 [Electronic] United States
• PMID: 21649487 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Artemisinins
• Ferrous Compounds
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• ferrous sulfate
• Artesunate

Topics

• Administration, Oral
• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Artemisinins (administration & dosage, pharmacology)
• Artesunate
• Dose-Response Relationship, Drug
• Drug Synergism
• Ferrous Compounds (administration & dosage, pharmacology)
• Liver (drug effects, metabolism)
• Liver Function Tests
• Male
• Mitochondria, Liver (drug effects, metabolism)
• Mitochondrial Membrane Transport Proteins (metabolism)
• Mitochondrial Permeability Transition Pore
• Rats