Department: Pharmacology, Physiology and Toxicology
Research Clusters: Cancer Biology; Cardiovascular Disease, Obesity, and Diabetes; Toxicology and Environmental Health Sciences (Research Cluster Coordinator)
Office: BBSC 435-G | Laboratory: BBSC 406
Phone: (304) 696-7332
Projects in my lab:
Project #1 Herbal agent reduction of drug side effects: Billions of dollars are spent yearly by individuals on nutritional supplements but the health effects of pharmaceuticals are not known. We are investigating the mechanism for reduction of hepatic acetaminophen (APAP) toxicity by S-adenosyl-l-methionine (SAMe). (Figure 1). APAP is the number one cause of drug induced liver failure in the U.S and we are interested in methods to reduce toxicity. This project is evaluating the cellular effects of SAMe that are responsible for attenuating acetaminophen toxicity. Figure 1 shows that SAMe when given 1 h after APAP reduces band intensity induced by protein carbonylation. Our studies are also comparing SAMe to the currently used clinical antidote, N-acetylcysteine for acetaminophen overdose to evaluate SAMe’s effectiveness.
Project #2: Developing new interventions to reduce cancer chemotherapeutic drug toxicity: This project is evaluating the protective effect of resveratrol on cisplatin nephrotoxicity. Cisplatin (Cis) is a widely used cancer chemotherapeutic agent. Unfortunately, over 30% of patients develop renal failure during cisplatin usage. We have found that resveratrol (RES) can reduce renal toxicity. We are evaluating whether resveratrol impacts cell signaling or alters oxidative stress as part of its protective effect against cisplatin. This project uses multiple experimental models including a human kidney proximal tubular cell line.
Project #3 Renal Impairment by environmental chemicals, drugs and their metabolites: Our laboratory is interested in the cellular mechanism of toxicity. We are examining the mechanism of renal toxicity by radiocontrast agents, acetaminophen metabolites as well as herbicide metabolites. Acetaminophen is converted by enzymes in the liver to a substance that is toxic to the kidney. We are investigating the role of oxidative stress and protein modification in 4-aminophenol renal toxicity. The proteins modified by 4-aminophenol may be deleterious to renal cell function.
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. This project is examining the predisposition to renal damage by renal toxicants that are known to induce free radical damage. This area of research is investigating the cellular and subcellular abnormalities induced by diabetes; and possible interventions to slow the progression of renal dysfunction.
Selected Publications since 2012
For a full list of publications, access PubMed
J.K. Lau, K.C. Brown, A.M. Dom, T.R. Witte, B.A. Thornhill, C.M. Crabtree, H.E. Perry, J.M. Brown, J.G. Ball, R.G. Creel, C.L. Damron, W.D. Rollyson, C.D. Stevenson, W.E. Hardman, M.A. Valentovic, A.B. Carpenter, P. Dasgupta. Capsaicin induces Apoptosis in Human Small Cell Lung Cancer via the TRPV6 Receptor and the Calpain Pathway. Apoptosis. 2014 (In Press).
G.O., Rankin and M.A. Valentovic, 2014. Kidney. In: Wexler, P. (Ed.), Encyclopedia of Toxicology, 3rd edition vol 3. Elsevier Inc., Academic Press, pp. 20–39.
Monica A. Valentovic, John G. Ball, J. Mike Brown, Marcus V. Terneus, Elizabeth McQuade, Stephanie Van Meter, Hayden M. Hedrick, Amy Allison Roy and Tierra Williams. Resveratrol Attenuates Cisplatin Renal Cortical Cytotoxicity by Modifying Oxidative Stress. Toxicology In Vitro 2014. 28:248-257.
Andrea D. Belalcázar, John G. Ball, Leslie M. Frost, Monica A. Valentovic and John Wilkinson, IV, “Transsulfuration Is a Significant Source of Sulfur for Glutathione Production in Human Mammary Epithelial Cells,” ISRN Biochemistry, vol. 2013, Article ID 637897, 7 pages, 2013.
J.M. Brown, John G. Ball, Michael Scott Wright, Stephanie Van Meter and M.A. Valentovic. Novel protective mechanisms for S-adenosyl-l-methionine against acetaminophen hepatotoxicity: Improvement of key antioxidant enzymatic function. Toxicology Letters 212: 320– 328, 2012 August 2012.
G.O. Rankin, S.K. Hong, D.K. Anestis, J.G. Ball and M. A. Valentovic..Role of leukotrienes in N-(3,5-dichlorophenyl) succinimide (NDPS) and NDPS metabolite nephrotoxicity in male Fisher 344 rats. Toxicology 2012 300:92-99.
Graduates from Valentovic Lab
J. Michael Brown, Ph.D., Pharm.D. (2012) – Pharmacy Fellow
Marcus Terneus, Ph.D. (2006) – Senior Manager, Global Environmental, Health and Safety Occupational Toxicology, Mylan [Pharmaceuticals]
R. Chris Harmon, M.D., Ph.D. (2003) – Gastroenterologist, Augusta Health
Sama Kalou, M.S., M.D. (2003)
Nizar Noureddine, M.S., Ph.D. (2002) – Cardiologist
Jennifer Minigh, Ph.D. (May 2002) Senior Manager Global Regulatory Writing, Amgen
Laurie Scott, Ph.D. (1989) Toxicologist Proctor and Gamble International