[Toxicology and tissue distribution of Ruthenium (II) CO-releasing molecules and its interaction with endogenous substances].
Carbon monoxide has been proved to be an important signal molecule in body. Transition metal carbonyl compounds are solidified form of carbon monoxide. Numerous studies have shown that Ruthenium carbonyl carbon monoxide releasing molecules have a strong pharmacological activity. In this paper, five Ruthenium (II) carbonyl CORMs 1-5 were synthesized and their toxicology, tissue distribution and interaction with blood endogenous substances were investigated. The results showed CORMs' IC50 to fibroblasts are ranged from 212.9 to 2089.2 micromol x L(-1). Their oral LD50 to mouse is between 800 to 1600 mg x kg(-1). After repeated administration, CORMs 1 and CORMs 5 haven't shown an obvious influence to rats' liver and kidney function, but caused the injury to liver and kidney cells. The in vivo distribution result revealed the majority of CORMs were distributed in blood, liver and kidney, only a small part of CORMs distributed in lung, heart and spleen. They could scarcely cross the blood-brain barrier and distribute to brain. The non-CO ligands in structure have an obvious relevance to their in vivo absorption and distribution. Interestingly, CORMs could enhance the fluorescence of bovine serum albumin, and this enhancement was in direct proportion with the concentration of CORMs. Under different conditions, interaction of CORMs with glutathione got different type of products, one is Ruthenium (II) tricarbonyl complexes, and Ruthenium (II) dicarbonyl complexes.
Institute of Medicinal Chemistry, School of Pharmacy, Lanzhou University, China.
Peng-peng
PP
Wang
Institute of Medicinal Chemistry, School of Pharmacy, Lanzhou University, China.
Hua-peng
HP
Liu
Institute of Medicinal Chemistry, School of Pharmacy, Lanzhou University, China.
Quan-yi
QY
Zhao
The First Hospital of Lanzhou University, China.
Yong-lin
YL
Chen
School ofStomatology, Lanzhou University, Lanzhou 730000, China.
Bin
B
Liu
School ofStomatology, Lanzhou University, Lanzhou 730000, China.
Bao-ping
BP
Zhang
School ofStomatology, Lanzhou University, Lanzhou 730000, China.
Qian
Q
Zheng
D000818:Animals; D002248:Carbon Monoxide / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012428:Ruthenium / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D014018:Tissue Distribution
D009942:Organometallic Compounds; D002248:Carbon Monoxide; D012428:Ruthenium