Deltamethrin-induced thymus atrophy in male Balb/c mice

Essam Enan, Kent E Pinkerton, Janice Peake, Fumio Matsumura

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The action of deltamethrin, a potent type II synthetic pyrethroid insecticide, on the thymus of the Balb/c mouse was studied in vivo and in vitro. We found that deltamethrin produced atrophy in the thymus in a dose- and time-dependent fashion. The lowest effective dose was found to be 6 mg/kg, 24 hr after a single intraperitoneal treatment. Treated animals did not recover during the time-course of the experiment (35 days after treatment); however, deltamethrin did not affect the body weight of the treated animals during the course of the study. To determine if deltamethrin-induced [Ca2+](i) signaling could lead to thymic atrophy via programmed cell death, mice were treated with 25 mg deltamethrin/kg for 24 hr or the isolated thymocyte suspension was treated with 50 μM deltamethrin. A significant stimulation of inositol 1,4,5-triphosphate (IP3) and inositol 1,4-diphosphate (IP2) production was found after 24 hr of deltamethrin-1R (active isomer) treatment. An inactive stereoisomer of deltamethrin (i.e. 1S) did not cause a significant rise in the production of IP3 and IP2. In addition, deltamethrin-1R induced a transient increase of [Ca2+](i) mobilization in the thymocyte suspension after 10 min of in vitro treatment, and substantially reduced the rate of calcium-calmodulin (Ca/CaM)-dependent protein dephosphorylation in in vivo treated animals (25 mg deltamethrin/kg for 24 hr). The in vivo effects of deltamethrin treatment demonstrated induction of DNA fragmentation and cell death in thymocytes. Moreover, using a histochemical approach, it was evident that deltamethrin at 25 mg/kg was able to produce cell death in the thymus of treated animals 72 hr after treatment. In the present work, we found that cell death was apoptotic in nature as noted first by the inhibition of deltamethrin-induced cell death by aurintricarboxylic acid, an inhibitor of apoptosis, and second, by internucleosomal DNA fragmentation, a hallmark of apoptosis, produced by deltamethrin in treated animals as well in thymocyte suspensions. In addition, the involvement of the Ca/CaM-dependent protein phosphorylation-dephosphorylation cascade in the induction of apoptosis by deltamethrin was supported by the protective role of the calmodulin inhibitor trifluoperazine against the apoptotic effect of deltamethrin on thymocyte suspension. Our results suggest that deltamethrin induced thymus atrophy and altered the Ca/CaM-dependent protein kinase-phosphatase cascade, which might induce programmed cell death.

Original languageEnglish (US)
Pages (from-to)447-454
Number of pages8
JournalBiochemical Pharmacology
Volume51
Issue number4
DOIs
StatePublished - Feb 23 1996

Fingerprint

Thymus
Thymus Gland
Atrophy
Cell death
Thymocytes
Cell Death
Animals
Suspensions
Calmodulin
decamethrin
DNA Fragmentation
Apoptosis
Aurintricarboxylic Acid
Calcium
Trifluoperazine
Pyrethrins
Calcium-Calmodulin-Dependent Protein Kinases
Phosphorylation
Stereoisomerism
Inositol 1,4,5-Trisphosphate

Keywords

  • apoptosis
  • deltamethrin
  • mice
  • protein dephosphorylation
  • thymus atrophy

ASJC Scopus subject areas

  • Pharmacology

Cite this

Deltamethrin-induced thymus atrophy in male Balb/c mice. / Enan, Essam; Pinkerton, Kent E; Peake, Janice; Matsumura, Fumio.

In: Biochemical Pharmacology, Vol. 51, No. 4, 23.02.1996, p. 447-454.

Research output: Contribution to journalArticle

Enan, Essam ; Pinkerton, Kent E ; Peake, Janice ; Matsumura, Fumio. / Deltamethrin-induced thymus atrophy in male Balb/c mice. In: Biochemical Pharmacology. 1996 ; Vol. 51, No. 4. pp. 447-454.
@article{fae7fe18599048c4bea332b51d806126,
title = "Deltamethrin-induced thymus atrophy in male Balb/c mice",
abstract = "The action of deltamethrin, a potent type II synthetic pyrethroid insecticide, on the thymus of the Balb/c mouse was studied in vivo and in vitro. We found that deltamethrin produced atrophy in the thymus in a dose- and time-dependent fashion. The lowest effective dose was found to be 6 mg/kg, 24 hr after a single intraperitoneal treatment. Treated animals did not recover during the time-course of the experiment (35 days after treatment); however, deltamethrin did not affect the body weight of the treated animals during the course of the study. To determine if deltamethrin-induced [Ca2+](i) signaling could lead to thymic atrophy via programmed cell death, mice were treated with 25 mg deltamethrin/kg for 24 hr or the isolated thymocyte suspension was treated with 50 μM deltamethrin. A significant stimulation of inositol 1,4,5-triphosphate (IP3) and inositol 1,4-diphosphate (IP2) production was found after 24 hr of deltamethrin-1R (active isomer) treatment. An inactive stereoisomer of deltamethrin (i.e. 1S) did not cause a significant rise in the production of IP3 and IP2. In addition, deltamethrin-1R induced a transient increase of [Ca2+](i) mobilization in the thymocyte suspension after 10 min of in vitro treatment, and substantially reduced the rate of calcium-calmodulin (Ca/CaM)-dependent protein dephosphorylation in in vivo treated animals (25 mg deltamethrin/kg for 24 hr). The in vivo effects of deltamethrin treatment demonstrated induction of DNA fragmentation and cell death in thymocytes. Moreover, using a histochemical approach, it was evident that deltamethrin at 25 mg/kg was able to produce cell death in the thymus of treated animals 72 hr after treatment. In the present work, we found that cell death was apoptotic in nature as noted first by the inhibition of deltamethrin-induced cell death by aurintricarboxylic acid, an inhibitor of apoptosis, and second, by internucleosomal DNA fragmentation, a hallmark of apoptosis, produced by deltamethrin in treated animals as well in thymocyte suspensions. In addition, the involvement of the Ca/CaM-dependent protein phosphorylation-dephosphorylation cascade in the induction of apoptosis by deltamethrin was supported by the protective role of the calmodulin inhibitor trifluoperazine against the apoptotic effect of deltamethrin on thymocyte suspension. Our results suggest that deltamethrin induced thymus atrophy and altered the Ca/CaM-dependent protein kinase-phosphatase cascade, which might induce programmed cell death.",
keywords = "apoptosis, deltamethrin, mice, protein dephosphorylation, thymus atrophy",
author = "Essam Enan and Pinkerton, {Kent E} and Janice Peake and Fumio Matsumura",
year = "1996",
month = "2",
day = "23",
doi = "10.1016/0006-2952(95)02200-7",
language = "English (US)",
volume = "51",
pages = "447--454",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Deltamethrin-induced thymus atrophy in male Balb/c mice

AU - Enan, Essam

AU - Pinkerton, Kent E

AU - Peake, Janice

AU - Matsumura, Fumio

PY - 1996/2/23

Y1 - 1996/2/23

N2 - The action of deltamethrin, a potent type II synthetic pyrethroid insecticide, on the thymus of the Balb/c mouse was studied in vivo and in vitro. We found that deltamethrin produced atrophy in the thymus in a dose- and time-dependent fashion. The lowest effective dose was found to be 6 mg/kg, 24 hr after a single intraperitoneal treatment. Treated animals did not recover during the time-course of the experiment (35 days after treatment); however, deltamethrin did not affect the body weight of the treated animals during the course of the study. To determine if deltamethrin-induced [Ca2+](i) signaling could lead to thymic atrophy via programmed cell death, mice were treated with 25 mg deltamethrin/kg for 24 hr or the isolated thymocyte suspension was treated with 50 μM deltamethrin. A significant stimulation of inositol 1,4,5-triphosphate (IP3) and inositol 1,4-diphosphate (IP2) production was found after 24 hr of deltamethrin-1R (active isomer) treatment. An inactive stereoisomer of deltamethrin (i.e. 1S) did not cause a significant rise in the production of IP3 and IP2. In addition, deltamethrin-1R induced a transient increase of [Ca2+](i) mobilization in the thymocyte suspension after 10 min of in vitro treatment, and substantially reduced the rate of calcium-calmodulin (Ca/CaM)-dependent protein dephosphorylation in in vivo treated animals (25 mg deltamethrin/kg for 24 hr). The in vivo effects of deltamethrin treatment demonstrated induction of DNA fragmentation and cell death in thymocytes. Moreover, using a histochemical approach, it was evident that deltamethrin at 25 mg/kg was able to produce cell death in the thymus of treated animals 72 hr after treatment. In the present work, we found that cell death was apoptotic in nature as noted first by the inhibition of deltamethrin-induced cell death by aurintricarboxylic acid, an inhibitor of apoptosis, and second, by internucleosomal DNA fragmentation, a hallmark of apoptosis, produced by deltamethrin in treated animals as well in thymocyte suspensions. In addition, the involvement of the Ca/CaM-dependent protein phosphorylation-dephosphorylation cascade in the induction of apoptosis by deltamethrin was supported by the protective role of the calmodulin inhibitor trifluoperazine against the apoptotic effect of deltamethrin on thymocyte suspension. Our results suggest that deltamethrin induced thymus atrophy and altered the Ca/CaM-dependent protein kinase-phosphatase cascade, which might induce programmed cell death.

AB - The action of deltamethrin, a potent type II synthetic pyrethroid insecticide, on the thymus of the Balb/c mouse was studied in vivo and in vitro. We found that deltamethrin produced atrophy in the thymus in a dose- and time-dependent fashion. The lowest effective dose was found to be 6 mg/kg, 24 hr after a single intraperitoneal treatment. Treated animals did not recover during the time-course of the experiment (35 days after treatment); however, deltamethrin did not affect the body weight of the treated animals during the course of the study. To determine if deltamethrin-induced [Ca2+](i) signaling could lead to thymic atrophy via programmed cell death, mice were treated with 25 mg deltamethrin/kg for 24 hr or the isolated thymocyte suspension was treated with 50 μM deltamethrin. A significant stimulation of inositol 1,4,5-triphosphate (IP3) and inositol 1,4-diphosphate (IP2) production was found after 24 hr of deltamethrin-1R (active isomer) treatment. An inactive stereoisomer of deltamethrin (i.e. 1S) did not cause a significant rise in the production of IP3 and IP2. In addition, deltamethrin-1R induced a transient increase of [Ca2+](i) mobilization in the thymocyte suspension after 10 min of in vitro treatment, and substantially reduced the rate of calcium-calmodulin (Ca/CaM)-dependent protein dephosphorylation in in vivo treated animals (25 mg deltamethrin/kg for 24 hr). The in vivo effects of deltamethrin treatment demonstrated induction of DNA fragmentation and cell death in thymocytes. Moreover, using a histochemical approach, it was evident that deltamethrin at 25 mg/kg was able to produce cell death in the thymus of treated animals 72 hr after treatment. In the present work, we found that cell death was apoptotic in nature as noted first by the inhibition of deltamethrin-induced cell death by aurintricarboxylic acid, an inhibitor of apoptosis, and second, by internucleosomal DNA fragmentation, a hallmark of apoptosis, produced by deltamethrin in treated animals as well in thymocyte suspensions. In addition, the involvement of the Ca/CaM-dependent protein phosphorylation-dephosphorylation cascade in the induction of apoptosis by deltamethrin was supported by the protective role of the calmodulin inhibitor trifluoperazine against the apoptotic effect of deltamethrin on thymocyte suspension. Our results suggest that deltamethrin induced thymus atrophy and altered the Ca/CaM-dependent protein kinase-phosphatase cascade, which might induce programmed cell death.

KW - apoptosis

KW - deltamethrin

KW - mice

KW - protein dephosphorylation

KW - thymus atrophy

UR - http://www.scopus.com/inward/record.url?scp=0030065478&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030065478&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(95)02200-7

DO - 10.1016/0006-2952(95)02200-7

M3 - Article

C2 - 8619889

AN - SCOPUS:0030065478

VL - 51

SP - 447

EP - 454

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 4

ER -