Antioxidant status and biomarkers of oxidative stress in canine lymphoma

Authors: WINTER, JENNIFER - TUFTS UNIVERSITY; BARBER, LISA - Tufts University; FREEMAN, LISA - TUFTS UNIVERSITY; GRIESSMAYR, PASCALE - TUFTS UNIVERSITY; Milbury, Paul; Blumberg, Jeffrey

Submitted to: Journal of Veterinary Internal Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/21/2008
Publication Date: 3/1/2009
Citation: Winter, J., Barber, L., Freeman, L., Griessmayr, P., Milbury, P., Blumberg, J. 2009. Antioxidant status and biomarkers of oxidative stress in canine lymphoma. Journal of Veterinary Internal Medicine. 23:311-316.

Interpretive Summary: An imbalance between the production of reactive oxygen and nitrogen molecules and the activity of antioxidant defenses, including the intake and tissue concentration of dietary antioxidants, results in a state of oxidative stress. Oxidative stress appears to play a role in the development of cancer and impact morbidity and mortality. This relationship appears both in humans and animal companions. Examining the relationship between cancer and oxidative stress in dogs may provide important insights to that in humans. Thus, we evaluated antioxidant concentrations and biomarkers of oxidative stress in dogs with newly-diagnosed lymphoma prior to treatment and once in remission, with comparison to healthy controls in a prospective, observational study. We found that at baseline, dogs with lymphoma (when compared to healthy dogs) had significantly lower plasma concentrations of vitamin E but higher activity of an antioxidant enzyme, glutathione peroxidase, and a measure of total antioxidant activity (Oxygen Radical Absorbance Capacity). These dogs also had high higher concentrations of plasma isoprostanes, an indicator of oxidative stress. In the dogs with lymphoma, vitamin E concentrations were higher and vitamin C concentrations were lower after treatment. Further studies are now warranted to determine whether treatment with dietary antioxidants may be beneficial in the treatment of lymphoma.

Technical Abstract: Background – Oxidative stress might play a role in carcinogenesis, as well as impacting morbidity and mortality of veterinary cancer patients. The purpose of this study was to evaluate antioxidant concentrations and biomarkers of oxidative stress in dogs with newly-diagnosed lymphoma prior to treatment and once in remission, with comparison to healthy controls. Hypothesis – Dogs with lymphoma have elevated oxidant and reduced antioxidant concentrations compared to healthy controls, and that these abnormalities normalize once remission is achieved. Animals – 17 dogs with lymphoma and 10 healthy controls. Methods – Prospective, observational study. Measures of oxidative stress [malondialdehyde (MDA) and total isoprostanes (isoP)] and antioxidants [alpha-tocopherol, gamma-tocopherol, Oxygen Radical Absorbance Capacity (ORAC), and glutathione peroxidase (GSHPx)] were assessed in dogs with newly diagnosed lymphoma before treatment compared to healthy control dogs. The same parameters were measured in the dogs with lymphoma on week 7 of the chemotherapy protocol when all dogs were in remission. Results – At baseline, dogs with lymphoma had significantly lower alpha-tocopherol (P<0.001) and gamma-tocopherol (P=0.003) but higher GSHPx (P=0.05), ORAC (P=0.001), and isoP (P<0.001) compared to healthy controls. In the dogs with lymphoma, alpha-tocopherol concentrations were higher (P=0.005) and ascorbic acid were lower (P=0.04) after treatment. Conclusions and Clinical Importance – Results suggest that dogs with lymphoma have alterations in oxidant and antioxidant concentrations and that the status of some of these biomarkers normalize after remission. Further studies are warranted to determine whether antioxidant interventions to correct these are beneficial in the treatment of canine lymphoma.