Monica Valentovic, Ph.D.
Professor of Pharmacology, Physiology and Toxicology
Joan C. Edwards School of Medicine, Marshall University
E-mail: valentov@marshall.edu
Phone: (304) 696-7332
Cluster Affiliations:Toxicology and Environmental Health Sciences; Cancer Biology; and Cardiovascular Disease, Obesity and Diabetes
Office: BBSC 435-G
Laboratory: BBSC 406
Department of Pharmacology, Physiology and Toxicology
Joan C. Edwards School of Medicine
One John Marshall Drive
Huntington, WV 25755
Projects currently ongoing in my lab:
Project 1. The effect of herbal agents on susceptibility to toxins: Billions of dollars are spent in the United States each year by individuals on nutritional and herbal supplements. We are investigating the mechanism for reduction of hepatic acetaminophen toxicity by S-adenosyl-l-methionine (SAMe). This project is important since acetaminophen is the number one cause of drug induced liver failure in the U.S. This project is evaluating the cellular effects of SAMe that are responsible for attenuating acetaminophen toxicity. We are also comparing SAMe to the currently used clinical treatment for acetaminophen to evaluate SAMe’s effectiveness.
Project 2. Evaluating methods to reduce the side effects of cancer chemotherapeutic drugs: This project is evaluating the protective effect of another natural product on cisplatin nephrotoxicity. Cisplatin is a widely used cancer chemotherapeutic agent. Unfortunately, the two principal side effects of cisplatin treatment are renal and peripheral nerve dysfunction. We have found an agent that can reduce the renal toxicity in isolated renal tissue. We are evaluating whether resveratrol impacts cell signaling or alters oxidative stress as part of its protective effect against cisplatin.
Project 3. Examination of the mechanism for kidney damage by a metabolite of acetaminophen (Tylenol): Acetaminophen is converted by enzymes in the liver to several different substances. One of these agents is toxic to the kidney. We are investigating the role of oxidative stress in induction of 4-aminophenol renal toxicity. Further studies are also evaluating possible agents to reduce renal toxicity. A second component of this project is to test the hypothesis that part of the mechanism for 4-aminophenol toxicity is mediated by protein modification. The proteins modified by 4-aminophenol, the sub cellular location of these proteins and the impact on cell function are being assessed to evaluate the mechanism of toxicity.
Project 4. Susceptibility to oxidative stress in diabetes: Over 1 in 50 Americans are diagnosed with diabetes mellitus. Diabetes is associated with a higher risk of kidney disease and renal failure. The predisposition to renal dysfunction may involve a defect in the ability to protect the kidney from damage by free radicals. A student would examine: a) the predisposition to renal damage by renal toxicants that are known to induce free radical damage; b) investigate the cellular and subcellular abnormalities induced by diabetes; c) initiate studies of possible interventions to slow the progression of renal dysfunction.
Select journal publications (from 77 published peer reviewed papers and 2 book chapters)
M.A. Valentovic, M.K. Meadows, R.C. Harmon, J.G. Ball, S. Stohl, S.K. Hong and G.O. Rankin. 2-Amino-5-chlorophenol toxicity in renal cortical slices from Fischer 344 rats: Effects of antioxidants and sulfhydryl agents. Toxicol. Appl. Pharmacol. 161: 1-9, 1999.
M.A. Valentovic and J. L. Minigh. Pyruvate attenuates myoglobin in vitro toxicity. Toxicological Sciences 74(2):345-51, 2003.
M., Valentovic, Terneus M, Harmon RC, Carpenter AB. S-Adenosylmethionine (SAMe) attenuates acetaminophen hepatotoxicity in C57BL/6 mice. Toxicol Lett. 154(3):165-74, 2004
R.C. Harmon, M. V. Terneus, K. K. Kiningham and M. Valentovic, Time Dependent Effect of p-Aminophenol (PAP) Toxicity in Renal Slices and Development of Oxidative Stress. Toxicol Appl Pharmacol. 2005 209(1):86-94, 2005.
R.C. Harmon, K.K. Kiningham and M.A. Valentovic. Pyruvate reduces 4- aminophenol in vitro toxicity. Toxicol. Appl. Pharmacol. 213(2):179-86,2006.
M.A. Valentovic, N. Alejandro, A. B. Carpenter, P.I. Brown and K.S. Ramos. Streptozotocin (STZ) Diabetes enhances benzo(alpha)pyrene induced renal injury in Sprague Dawley rats. Toxicol. Lett. 164(3):214-20, 2006.