Drug-induced vascular injury

Kerns W, et al. Drug-induced vascular injury - a quest for biomarkers. Toxicol Appl Pharmacol. 2005 203 62-87. 

Brott, D. A., H. B. Jones, S. Gould, J-P. Valentin, G. O. Evans, R. J. Richardson, and C. Louden. 2004. Current status and future directions for diagnostic markers of drug-induced vascular injury. Disease Markers 18 1-14. 

HISTORICAL CONTEXT OF DRUG-INDUCED VASCULAR INJURY AND DRUG DEVELOPMENT... 

TABLE 25.1 Examples of Drug-Induced Vascular Injury Identified in Preclinical Safety Studies According to the Preclinical Species, Mechanism of Toxicity, Vascular Beds Affected, and Microscopic Findings... 

Dahnas, D. A., Scicchitano, M. S., Mullins, D., Hughes-Earle, A., Tatsuoka, K., Magid-Slav, M., Frazier, K. S., and Thomas, H. C. (2011). Potential candidate genomic biomarkers of drug induced vascular injury in the rat. Toxicol Appl Pharmacol 257, 284-300. 

Enerson, B. E., Lin, A., Lu, B., Zhao, H., Lawton, M. R, and Floyd, E. (2006). Acute drug-induced vascular injury in heagle dogs pathology and correlating genomic expression. Toxicol Pathol 34, 27-32. 

Engelhardt, J. A., Fant, R, Guionaud, S., Henry, S. R, Leach, M. W., Louden, C., Scicchitano, M. S., Weaver, J. L., Zahka, T. S., and Frazier, K. S. (2015). Scientific and Regulatory Rolicy Committee Points-to-consider Paper Drug-induced vascular injury associated with nonsmall molecule therapeutics in pre-clinical development Part 2. Antisense oligonucleotides. Toxicol Pathol 43, 935 44. 

Louden, C., Brott, D., Katein A, Kelly T., Gould, S., Jones, H., Betton, G., Valetin, J. R, and Richardson, R. J. (2006). Biomarkers and mechanisms of drug-induced vascular injury in non-rodents. Toxicol Pathol 34(1), 19-26. 

Morton, D., Houle, C. D., and Tomlinson, L. (2014). Perspectives on drug-induced vascular injury. Toxicol Pathol 42, 633-4. 

Zhang, J., Hanig, J. R, and De Felice, A. F. (2012). Biomarkers of endothelial cell activation Candidate markers for drug-induced vasculitis in patients or drug-induced vascular injury in animals. Vascul Pharmacol 56, 14-25. 

When analyzed as a whole, the data about acute TAC nephrotoxicity suggest that although the net effect of this drug on vascular reactivity, tubular cells and renal function is similar to that caused by CSA, the mechanisms of TAC-induced functional renal injury are probably distinct from those implicated in CSA-induced acute nephrotoxicity. 

Case Study 2 Drug Candidate-Induced Micro vascular Injury at the Exocrine-Endocrine Interface in the Rat with Unsuccessful Confirmation of Toxicity In Vitro and No Pancreas-Specific Monitorable Biomarkers Identified... 

The mechanisms responsible for the contractile responses to AmB have not been identified. Theoretically, the drug can act either directly on the vascular smooth muscle or through release of secondary mediators. A large number of studies have examined putative indirect mechanisms of action. Those studies have revealed that neither renal denervation nor angiotensin II receptor blockade prevent the renal vasoconstriction or the reduction in GFR [87, 88]. Although Cutaia et al [89] demonstrated a toxic effect of AmB on endothelial cells, endothelin does not appear to be involved in the acute responses to AmB [88, 90] and reduced nitric oxide synthesis, consequent to endothelial injury is not involved in modulation of AmB-induced renal vasoconstriction [88]. 

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