Deniz Satar1, Salim Satar2, Ufuk Ozgu Mete3, Jeffrey R Suchard4, Metin Topal2, Emre Karakoc5, Mehmet Kaya3. 1. Pathology Department, Adana Numune Education and Research Hospital, Adana, Turkey. 2. Department of Emergency Medicine, Cukurova University School of Medicine, Adana, Turkey. 3. Department of Histology and Embryology, Cukurova University School of Medicine, Adana, Turkey. 4. Department of Emergency Medicine, University of California Irvine Medical Center, Orange, California. 5. Department of Medical Intensive Care, Cukurova University School of Medicine, Adana, Turkey.
Abstract
BACKGROUND: Organophosphate (OP) insecticides are widely used in both agricultural and landscape pest control, and the potential for human exposure to these compounds is significant. OBJECTIVES: The aims of this study were to investigate the effects of acute poisoning with the OP methamidophos and the effects of antidotal therapy with atropine and pralidoxime on rat thyroid tissue ultrastructure. METHODS: In this single-blind, ex vivo study, male Wistar albino rats weighing 220 to 230 g were divided into 4 treatment groups. Group 1 received a median lethal dose of methamidophos (30 mg/kg) via oral gavage. Group 2 received saline via oral gavage and served as the control group for group 1. Group 3 received methamidophos (30 mg/kg) via oral gavage, and after 8 minutes atropine 0.05 mg/kg and pralidoxime chloride (2-FAM) (40 mg/kg) were administered intraperitoneally (IP). Atropine was titrated to reverse signs of cholinergic excess. Group 4 received saline via oral gavage followed by IP injections and served as the control for group 3. Rat thyroid tissues were examined using electron microscopy, and the histologic changes were examined by a histopathologist who was blinded to treatment. All rats were euthanized by intracardiac blood collection. The rats in groups 1 and 2 were euthanized 8 minutes after treatment. The rats in groups 3 and 4 were euthanized 96 hours after treatment. RESULTS: Thirty-four male rats (aged 16 weeks) were included in the study. The rats were grouped accordingly: group 1 (n = 10); group 2 (n = 7); group 3 (n = 10); and group 4 (n = 7). The mean (SD) pseudocholinesterase (FCE) activity was significantly lower in the methamidophos-treated rats (group 1) compared with the corresponding control group (group 2) (32.6 [17.0] vs 579.4 [59.0] U/L, respectively; P < 0.001). PCE activity was significantly higher in rats treated with atropine and 2-PAM (group 3) (392.5 [39.4] U/L; P < 0.001) compared with those not receiving antidotal therapy (group 1). Group 1 experienced changes in thyrocytes and organelles that were not detected in the antidote-treated rats in group 3. These changes included follicular cell nuclei exhibiting an increase in chromatin content, pyknotic nuclei, mitochondrial degeneration, dilated granular endoplasmic reticulum cisternae, reduced microvilli, and intraluminal cellular debris. Within follicular cells, formation of vacuoles filled with fine granular material was noted. CONCLUSION: Acute OP poisoning was associated with histopathologic effects in rat thyroid tissue that appeared to be mitigated by antidotal therapy in this small animal study. More extensive studies using immunohistochemical methods are needed.
BACKGROUND:Organophosphate (OP) insecticides are widely used in both agricultural and landscape pest control, and the potential for human exposure to these compounds is significant. OBJECTIVES: The aims of this study were to investigate the effects of acute poisoning with the OP methamidophos and the effects of antidotal therapy with atropine and pralidoxime on rat thyroid tissue ultrastructure. METHODS: In this single-blind, ex vivo study, male Wistar albino rats weighing 220 to 230 g were divided into 4 treatment groups. Group 1 received a median lethal dose of methamidophos (30 mg/kg) via oral gavage. Group 2 received saline via oral gavage and served as the control group for group 1. Group 3 received methamidophos (30 mg/kg) via oral gavage, and after 8 minutes atropine 0.05 mg/kg and pralidoxime chloride (2-FAM) (40 mg/kg) were administered intraperitoneally (IP). Atropine was titrated to reverse signs of cholinergic excess. Group 4 received saline via oral gavage followed by IP injections and served as the control for group 3. Rat thyroid tissues were examined using electron microscopy, and the histologic changes were examined by a histopathologist who was blinded to treatment. All rats were euthanized by intracardiac blood collection. The rats in groups 1 and 2 were euthanized 8 minutes after treatment. The rats in groups 3 and 4 were euthanized 96 hours after treatment. RESULTS: Thirty-four male rats (aged 16 weeks) were included in the study. The rats were grouped accordingly: group 1 (n = 10); group 2 (n = 7); group 3 (n = 10); and group 4 (n = 7). The mean (SD) pseudocholinesterase (FCE) activity was significantly lower in the methamidophos-treated rats (group 1) compared with the corresponding control group (group 2) (32.6 [17.0] vs 579.4 [59.0] U/L, respectively; P < 0.001). PCE activity was significantly higher in rats treated with atropine and 2-PAM (group 3) (392.5 [39.4] U/L; P < 0.001) compared with those not receiving antidotal therapy (group 1). Group 1 experienced changes in thyrocytes and organelles that were not detected in the antidote-treated rats in group 3. These changes included follicular cell nuclei exhibiting an increase in chromatin content, pyknotic nuclei, mitochondrial degeneration, dilated granular endoplasmic reticulum cisternae, reduced microvilli, and intraluminal cellular debris. Within follicular cells, formation of vacuoles filled with fine granular material was noted. CONCLUSION: Acute OP poisoning was associated with histopathologic effects in rat thyroid tissue that appeared to be mitigated by antidotal therapy in this small animal study. More extensive studies using immunohistochemical methods are needed.