Abstract

We hope to clarify the molecular events occurring during cardiovascular injury by continuing our experimental work on the potent cardiovascular toxin, allylamine, and expanding our laboratory's work to in vitro cell culture systems, the investigation of myocardial ischemia, and other cardiovascular toxins. To further study allylamine (AA), we will isolate and definitively identify its hypothesized urinary metabolites, study the hypothetical role of Benzylamine oxidase and the monoamine oxidase systems by histochemical, ultracytochemical, and biochemical means in our acute and chronic rat models of AA cardiovascular toxicity. Continued morphologic studies of AA lesions will focus on acute endothelial and smooth muscle effects, using H3-Thymidine to assess hypothetical nuclear activation by AA's toxic metabolite, acrolein. Applying our methods of cardiovascular toxicology to endothelial smooth muscle, and possibly myocardial cell culture systems, we will investigate the metabolism of AA, toxicity of its metabolites, and we will attempt to assess metaplasia induced in these systems in parallel to the in vivo cartilagenous and bony metaplasia we have observed. Glutathione - both reduced and oxidized - and glutathione peroxidase, transferase and reductase will be studied in an ischemic myocardial dog model. Continued basic morphologic and toxicologic studies of other aliphatic amines, and other cardiotoxic compounds will be done.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL026189-11
Application #
3338507
Study Section
Pathology A Study Section (PTHA)
Project Start
1980-07-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1992-06-30
Support Year
11
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555

  Publications

Salabei, Joshua K; Balakumaran, Arun; Frey, Justin C et al. (2012) Verapamil stereoisomers induce antiproliferative effects in vascular smooth muscle cells via autophagy. Toxicol Appl Pharmacol 262:265-72
Langford, S D; Trent, M B; Balakumaran, A et al. (1999) Developmental vasculotoxicity associated with inhibition of semicarbazide-sensitive amine oxidase. Toxicol Appl Pharmacol 155:237-44
He, N; Singhal, S S; Awasthi, S et al. (1999) Role of glutathione S-transferase 8-8 in allylamine resistance of vascular smooth muscle cells in vitro. Toxicol Appl Pharmacol 158:177-85
Conklin, D J; Boor, P J (1998) Allylamine cardiovascular toxicity: evidence for aberrant vasoreactivity in rats. Toxicol Appl Pharmacol 148:245-51
Awasthi, S; Boor, P J (1998) Allylamine and beta-aminopropionitrile-induced vascular injury: enhanced expression of high-molecular-weight proteins. J Toxicol Environ Health A 53:61-76
Kumar, D; Trent, M B; Boor, P J (1998) Allylamine and beta-aminopropionitrile induced aortic medial necrosis: mechanisms of synergism. Toxicology 125:107-15
He, N G; Awasthi, S; Singhal, S S et al. (1998) The role of glutathione S-transferases as a defense against reactive electrophiles in the blood vessel wall. Toxicol Appl Pharmacol 152:83-9
Khan, M F; Green, S M; Ansari, G A et al. (1998) Phenylhydroxylamine: role in aniline-associated splenic oxidative stress and induction of subendocardial necrosis. Toxicol Sci 42:64-71
Khan, M F; Boor, P J; Gu, Y et al. (1997) Oxidative stress in the splenotoxicity of aniline. Fundam Appl Toxicol 35:22-30
Langford, S D; Boor, P J (1996) Oleander toxicity: an examination of human and animal toxic exposures. Toxicology 109:1-13

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