Evaluation of urinary corticosterone as a biomarker of stress in rats using fenitrothion as a chemical stressor
| Autor: | Jean-Martin Lapointe, Patricia A. Snyder, William J. Reagan |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Drug-Related Side Effects and Adverse Reactions 040301 veterinary sciences Urinary system Immunology Spleen Urine Thymus Gland Toxicology Fenitrothion 0403 veterinary science Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Immune system Corticosterone Stress Physiological Internal medicine medicine Adverse Drug Reaction Reporting Systems Animals business.industry Body Weight 04 agricultural and veterinary sciences Rats 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry Toxicity Biomarker (medicine) business Biomarkers Immunosuppressive Agents |
| Zdroj: | Journal of immunotoxicology. 13(3) |
| ISSN: | 1547-6901 |
| Popis: | Regulatory guidelines for pharmaceutical toxicity studies recommend using one dose near the maximum tolerated. At that level significant toxicities may occur, leading to systemic stress and secondary immune suppression which can be difficult to differentiate from a primary drug effect. Therefore, there is a need for a biomarker of stress applicable to toxicity studies. This study evaluated urinary corticosterone as a biomarker, using as a pharmacologic stressor fenitrothion, which was previously shown not to cause primary immune suppression. Rats were administered fenitrothion orally at 20 and 30 mg/kg daily for 2 or 8 days, with matched vehicle controls (n = 6/group). Urine was collected for 6 and 24 h, before treatment and on Day 2 and Day 8. Urine was assayed for corticosterone, separately for the first 6 h of collection and for the whole 24 h sample. Animals were euthanized on Day 3 or Day 9 and lymphoid tissue samples were collected, weighed and examined histologically. Treated rats showed neurologic signs following treatment. Findings also included time- and dose-dependent decreases in body weight and spleen and thymus weight decreases supra-proportional to body weight on Day 9. Histologic changes were mild at a dose of 20 mg/kg, but significant at 30 mg/kg, consisting of lymphocytolysis at Day 3 and lymphoid depletion at Day 9. Urine corticosterone levels were increased on Day 2 and Day 8, in the 6-h samples, but not the 24-h ones, at both dose levels. Based on the results, urine corticosterone appears to be a sensitive biomarker of systemic stress caused by fenitrothion. Other chemical stressors should be evaluated in a similar manner in order to fully validate urine corticosterone measurement as a stress biomarker. |
| Databáze: | OpenAIRE |
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