Krol Research Group

Welcome to the home page for the research group of Dr. Ed Krol. My lab and office are both situated on the third floor of the Health Sciences building at the University of Saskatchewan.

I accept graduate students from a wide variety of academic backgrounds in the basic sciences including chemistry, biochemistry, biology, toxicology, pharmacology, and physiology to name a few. For more information regarding graduate studies in my group, please visit the graduate studies portion of my website.

For more information contact us at ed.krol@usask.ca or (306) 966-2011.

Academic Background
Ed Krol

Academic Positions

2008-present: Associate Professor, College of Pharmacy & Nutrition, University of Saskatchewan
2001-2008:Assistant Professor, College of Pharmacy & Nutrition, University of Saskatchewan
2001-present: Associate Member, Department of Chemistry, University of Saskatchewan
2001-present: Member, Toxicology Graduate Program, University of Saskatchewan
2008-present: Member, Drug Design and Discovery Research Group, University of Saskatchewan
2011-present: Graduate Chair (Pharmacy)
2000-2001: Assistant Professor, Department of Chemistry, Brandon University

Education

BSc. 1985 (Chemistry) McMaster University

Ph.D. 1993 (Chemistry) Queen's University

Thesis: "Hydrolylsis of Phosphonformate Triesters: Rate Acceleration of a Millionfold in Nucleophilic Substitution at Phosphorus."
Supervisor: Gregory R.J. Thatcher

Postdoctoral

1994-1996: University of Illinois-Chicago, College of Pharmacy, Department of Medicinal Chemistry & Pharmacognosy
Supervisor: Judy L. Bolton
Research: Toxicology of quinones

1996-2000: University of Arizona, College of Pharmacy, Department of Pharmacology & Toxicology
Supervisor: Daniel C. Liebler
Research: Photoprotective and antioxidant properties of melanin and vitamin E


Societies

Chemical Institute of Canada (1996)
Society of Toxicology of Canada (2000)
American Chemical Society (1995)
International Society for the Study of Xenobiotics (2003)


Contact Information

Dr. Ed S. Krol
College of Pharmacy & Nutrition
University of Saskatchewan
Saskatoon, SK S7N 5C9
phone 306-966-2011
fax 306-966-6377
email

 

Research Interests

Protective Properties of Flaxseed Lignans

Flaxseed, which is grown as either an oil or a fibre crop, is important to the agricultural economy of Saskatchewan. Flaxseed consumption has been associated with a number of health benefits including a decreased risk of colon and breast cancer and a reduction of LDL cholesterol levels. A number of studies have been carried out over the years which have demonstrated the potential health benefits of alpha-linolenic acid which is present in flax oil. Our research is concerned with the properties of polyphenolic compounds (called lignans) present in flaxseed.

Secoisolariciresinol is the major lignan in flaxseed, present as the diglucoside form, and has demonstrated hydroxyl radical scavenging properties, reduction of mammary tumor growth, a decrease in the growth of metastatic lung tumors and the inhibition of type II diabetes. Secoisolariciresinol is metabolized by intestinal bacteria to the mammalian lignans enterodiol and enterolactone (Figure 1). Enterodiol and enterolactone may also be important contributors to chemoprevention as they have been shown to display antioxidant properties and to inhibit the growth of a variety of tumor cells.

                       
Figure 1

Figure 1.

We presently have two projects underway in collaboration with Dr. Jane Alcorn.

  1. We are investigating the pharmacokinetics of enterolactone glucuronidation. This work is currently being carried out by an MSc. student (C. Lin) and is supported by a UofS-BIT scholarship.
  2. We are studying the cytotoxicity of enterolactone and its metabolites in prostate and breast cancer cell lines.This work is being carried out by a Ph.D. student (Y. Di) and is supported by a College of Pharmacy & Nutrition Research Grant.

Reactive Intermediates

Naturally occurring plant polyphenols have recently received a great deal of attention for the potential health benefits they may provide. Limited regulatory guidelines currently exist for non-prescription, natural supplements. Unfortunately, numerous natural supplements are also toxic. For safety reasons, a comprehensive study of the reactivity of these naturally occurring compounds in natural supplements is crucial.

We are interested in studying nordihydroguaiaretic acid (NDGA) (Figure 2), a lignan found in the creosote bush that is found in the herbal supplement chapparal. Chapparal use has been associated with acute kidney and liver toxicity and it is believed that NDGA is responsible for the toxic effects. We plan to investigate the ability of NDGA to form reactive quinone intermediates and determine their relative toxicity compared to other lignans.

Figure 2

Figure 2

We currently have two projects underway in this area.

  1. Quinones that can be formed by several analogues of NDGA, including secoisolariciresinol, will be examined. The synthesis of NDGA lignan analogues is currently underway, some of which are substituted on only one ring are being prepared. The ability of these compounds to form quinones will be examined. This work is being performed by a Ph.D. student (I. Asiamah) and is funded by NSERC, University of Cape Coast and a College of Pharmacy & Nutrition GTF.
  2. NDGA analogues in which the alkyl chain substituents are modified are being prepared to determine their oxidative stability. This work is being performed by a summer undergraduate researcher (H. Hodgson) and is funded by NSERC and an NSERC-USRA.

Photoprotective Natural Products

Flavonols such as quercetin and kaempferol (Figure 3) are found in many plants and their levels in plants correlate with exposure of the plant to ultraviolet(UV) radiation, presumably as a means to minimize UV-induced damage. We are interested in learning how these flavonoids protect against UV-induced biological damage and their potential role as topical sunscreens. UV radiation can cause damage to biological systems in a number of ways including the formation of thymine cyclobutane dimers in DNA and through the formation of reactive oxygen species which can promote cellular oxidative damage.

Figure 3

Figure 3

There is currently one project underway in this area.

We are determining the ability of several flavonols to inhibit the formation of thymine dimers in vitro. An APCI-MS method has been validated to measure thymine dimer formation and is being used to measure UV-induced thymine dimer formation in EpiDerm(TM). We are also systematically studying the stability of flavonols to UV and aqueous conditions. This research is being performed by an MSc. student (S. Maini) and is supported by NSERC and a College of Pharmacy & Nutrition GTA.

 

Courses

Pharmacy Undergraduate Courses

PHARM 456.7: Pharmacotherapeutics II
Module V: Medicinal chemistry of cardiovascular drugs
Module VI: Medicinal chemistry of drugs for the treatment of thrombosis

PHARM 557.6: Pharmacotherapeutics III
Module X: Medicinal chemistry of drugs for the treatment of arthritis, rheumatology and musculoskeletal disorders
Module XI: Medicinal chemistry of drugs for the treatment of neurological disorders
Module XII: Medicinal chemistry of drugs in cancer chemotherapy
Module XIII: Medicinal chemistry of drugs for the treatment of psychiatric disorders

Pharmacy Graduate Courses

PHARM 832.3: Drug Design

PHARM 841.3: Selected Topics in Pharmaceutical Sciences
Medicinal chemistry and drug discovery; proteomics

PHARM 854.3: Xenobiotic Metabolism
Phase 1 and Phase 2 metabolizing enzymes

Chemistry Undergraduate Courses

CHEM 255.3: Bio-Organic Chemistry
Part III: Medicinal Chemistry

 

People in the Lab
Under Construction
Graduate Studies

I accept graduate students from a wide variety of academic backgrounds in the basic sciences including chemistry, biochemistry, biology, toxicology, pharmacology and physiology to name a few. Students with nationally competitive scholarships such as NSERC or CIHR receive tuition waivers from the College.

As a graduate student in my lab you would receive training in several of the following areas:

  • drug metabolism
  • analytical method development
  • product purification andidentification
  • animal studies
  • organic synthesis
  • physical-organic chemistry

HPLC

A majority of the work in my lab requires the use of HPLC. We have several instruments including a Waters Alliance system, shown here.
The Alliance system was purchased with funds from CFI

We also have access to the Saskatchewan Structural Sciences Centre (SSSC) which is conveniently located in the Thorvaldson building. We utilize the NMR and MS facilities in the SSSC extensively.

My research group holds group meetings and literature review meetings on alternate weeks throughout the year.

I am an Associate member of the Department of Chemistry and a member of the Toxicology Graduate Program. Therefore, students may also join my research group through these programs.

For information regarding application for graduate studies in the College of Pharmacy & Nutrition please click here.

 

Publications
  1. Sabia Maini, Heather L. Hodgson and Ed S. Krol, The UVA and aqueous stability of flavonoids is dependent on B-ring substitution. J. Agric. Food Chem. http://dx.doi.org/10.1021/jf3016128.
  2. Farah S. Hosseinian, Ed S. Krol and B. David Oomah, ."Bioactivity of Flaxseed Lignans". In Understanding Plant Bioactives in Food Systems. Florence O. Uruakpa, Ed. (2012)
  3. Jennifer Billinsky, Katherine Maloney, Ed Krol and Jane Alcorn, "A Comparison Between Lignans from Creosote Bush and Flaxseed and Their Potential to Inhibit Cytochrome P450 Enzyme Activity" In Drug Discovery Research in Pharmacognosy, 145-164, Omboon Vallisuta, Suleiman M. Olomat, Ed. (2011)
  4. Brian M. Fahlman and Ed S. Krol, "UVA and UVB Radiation-Induced Oxidation Products of Quercetin", J. Photochem. Photobiol. B, 97, 123-131 (2009)
  5. Brian M. Fahlman and Ed S. Krol, "Inhibition of UVA and UVB radiation-induced lipid oxidation by quercetin", J. Agric. Food Chem., 57 (12), 5301-5305 (2009)
  6. Lifeng Chen, Katie Maloney, Ed S. Krol, Anne E. Desjardins and Jian Yang, "Cloning, Overexpression, Purification and Characterization of the Maleylacetate Reductase (PcpE) from Sphingobium chlorophenolicum Strain ATCC 53874." Curr. Microbiol., 58 (6), 599-603 (2009)
  7. Melanie A. Felmlee, Gloria Woo, Elmer Simko, Ed S. Krol, Alister D. Muir and Jane Alcorn, "Effects of the flaxseed lignans secoisolariciresinol diglucoside and its aglycone on serum and hepatic lipids in hyperlipidemic rats." Br. J. Nutr., 102 (3), 361-369 (2009).
  8. Jennifer L. Billinsky and Ed S. Krol, "Nordihydroguaiaretic acid autoxidation produces a schisandrin-like dibenzocyclooctadiene lignan." J. Nat. Prod., 71 (9) 1612-1615 (2008)
  9. Jennifer L. Billinsky, Michelle R. Marcoux and Ed S. Krol, "Oxidation of the Lignan Nordihydroguaiaretic Acid." Chem. Res. Toxicol., 20 (9), 1352-1358 (2007)
  10. Farah S. Hosseinian, Alister D. Muir, Neil D. Westcott and Ed S. Krol, "AAPH-mediated antioxidant reactions of secoisolariciresinol and SDG." Org. Biomol. Chem., 5 (4), 644-654 (2007)
  11. Farah S. Hosseinian, Alister D. Muir, Neil D. Westcott and Ed S. Krol, "Antioxidant Capacity of Flaxseed Lignans in Two Model Systems.", J. Am. Oil Chem. Soc., 83 (10) 835-840 (2006)
  12. Ed S. Krol, Daniel D.J. Escalante and Daniel C. Liebler, “Mechanisms of Dimer and Trimer Formation from Ultraviolet-Irradiated alpha-Tocopherol.”, Lipids , 36 (1) 49-55 (2001)
  13. Ed S. Krol, Kimberly Kramer-Stickland and Daniel C. Liebler, “Photoprotective Actions of Topically Applied Vitamin E.” Drug Metabolism Reviews , 32 (3&4), 413-420 (2000)

Selected Conference Presentations

  1. Sabia Maini, Heather L. Hodgson and Ed S. Krol, 2012. "The UVA and Aqueous Stability of Flavonols Under Investigation as Topical Skin Photoprotectants", 95th Chemical Society of Canada Conference and Exhibition, Abstract 506, Calgary, AB, (May 26-30, 2012).
  2. Isaac Asiamah, Katherine A. Maloney and Ed S. Krol, "Enhancing Therapeutic Potentials of Nordihydroguaiaretic acid (NDGA) through Synthesis and Metabolism Studies of novel Phenol and Catechol NDGA Analogues", 95th Chemical Society of Canada Conference and Exhibition, Abstract 1060, Calgary, AB, (May 26-30, 2012).
  3. Sabia Maini, Brian M. Fahlman and Ed S. Krol, "HPLC-MS/MS method to quantitate cyclobutane thymine dimers in a UV exposed reconstructed human skin model", 95th Chemical Society of Canada Conference and Exhibition, Abstract 1383, Calgary, AB, (May 26-30, 2012).
  4. Sabia Maini, Mark Berry and Ed S. Krol, "HPLC-MS/MS Method to Quantitate Pharmacologically Active Trace Amines in Rat Brain", 47th Western Canada Trace Analytical Workshop, Saskatoon, SK, (April 22-25, 2012).
  5. Jessie Lin, Ed S. Krol and Jane Alcorn, "Hepatic and Intestinal Glucuronidation of Enterolactone derived from Flaxseed Lignans", 64th Flax Institute, Fargo, ND, (March 29-30, 2012).
  6. Jatinder Mukker, Yunyun Di, Ed S. Krol and Jane Alcorn, "Effect of Enterolactone and Enterolactone Glucuronide on the Selective Cytotoxicity and Inhibition of Fatty Acid Synthase in Prostate and Breast Cancer cell lines", 64th Flax Institute, Fargo, ND, (March 29-30, 2012).
  7. Jatinder Kaur Mukker, Deborah Michel, Ed. S. Krol, Alister D Muir and J. Alcorn, "Intestinal Permeability, Uptake and Metabolism of Flaxseed and Mammalian Lignans in the Caco-2 Cell Monolayer", Association of Faculties of Pharmacy of Canada Annual Conference, Richmond, BC, (June 2-4, 2010).
  8. Gail Cunningham, Mark Jacobson, Ed S. Krol, "Investigation of a Case of PCV2 Vaccine Dilution and Theft", 21st International Pig Veterinary Society Annual Congress, Vancouver, BC, (July 18-21, 2010).