Impact of experimental type 1 diabetes mellitus on systemic and coagulation vulnerability in mice acutely exposed to diesel exhaust particles

Abderrahim Nemmar, Deepa Subramaniyan, Javed Yasin, Badreldin H. Ali

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Epidemiological evidence indicates that diabetic patients have increased susceptibility to adverse cardiovascular outcomes related to acute increases in exposures to particulate air pollution. However, mechanisms underlying these effects remain unclear.Methods: To evaluate the possible mechanisms underlying these actions, we assessed the systemic effects of diesel exhaust particles (DEP) in control mice, and mice with streptozotocin-induced type 1 diabetes. Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4 mg/kg) or saline, and several cardiovascular endpoints were measured 24 h thereafter.Results: DEP caused leukocytosis and a significant increase in plasma C-reactive protein and 8-isoprostane concentrations in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. The arterial PO2 as well as the number of platelets and the thrombotic occlusion time in pial arterioles assessed in vivo were significantly decreased following the i.t. instillation of DEP in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. Both alanine aminotransferase and aspartate transaminase activities, as well as the plasma concentrations of plasminogen activator inhibitor and von Willebrand factor were significantly increased in DEP-exposed diabetic mice compared to diabetic mice exposed to saline or DEP-exposed non-diabetic mice. The in vitro addition of DEP (0.25-1 μg/ml) to untreated mouse blood significantly and dose-dependently induced in vitro platelet aggregation, and these effects were exacerbated in blood of diabetic mice.Conclusion: This study has shown that systemic and coagulation events are aggravated by type 1 diabetes in mice, acutely exposed to DEP and has described the possible mechanisms for these actions that may also be relevant to the exacerbation of cardiovascular morbidity accompanying particulate air pollution in diabetic patients.

Original languageEnglish
Article number14
JournalParticle and Fibre Toxicology
Volume10
Issue number1
DOIs
Publication statusPublished - Apr 15 2013

Fingerprint

Vehicle Emissions
Experimental Diabetes Mellitus
Medical problems
Coagulation
Type 1 Diabetes Mellitus
8-epi-prostaglandin F2alpha
Platelets
Air pollution
Blood
Air Pollution
Alanine Transaminase
Plasmas
Plasminogen Inactivators
von Willebrand Factor
Streptozocin
Aspartate Aminotransferases
C-Reactive Protein
Animals
Leukocytosis
Agglomeration

Keywords

  • Air pollution
  • Diesel exhaust particles
  • Mice
  • Platelet aggregation
  • Streptozotocin
  • Thrombosis
  • Type 1 diabetes

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Toxicology
  • Medicine(all)

Cite this

Impact of experimental type 1 diabetes mellitus on systemic and coagulation vulnerability in mice acutely exposed to diesel exhaust particles. / Nemmar, Abderrahim; Subramaniyan, Deepa; Yasin, Javed; Ali, Badreldin H.

In: Particle and Fibre Toxicology, Vol. 10, No. 1, 14, 15.04.2013.

Research output: Contribution to journalArticle

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abstract = "Background: Epidemiological evidence indicates that diabetic patients have increased susceptibility to adverse cardiovascular outcomes related to acute increases in exposures to particulate air pollution. However, mechanisms underlying these effects remain unclear.Methods: To evaluate the possible mechanisms underlying these actions, we assessed the systemic effects of diesel exhaust particles (DEP) in control mice, and mice with streptozotocin-induced type 1 diabetes. Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4 mg/kg) or saline, and several cardiovascular endpoints were measured 24 h thereafter.Results: DEP caused leukocytosis and a significant increase in plasma C-reactive protein and 8-isoprostane concentrations in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. The arterial PO2 as well as the number of platelets and the thrombotic occlusion time in pial arterioles assessed in vivo were significantly decreased following the i.t. instillation of DEP in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. Both alanine aminotransferase and aspartate transaminase activities, as well as the plasma concentrations of plasminogen activator inhibitor and von Willebrand factor were significantly increased in DEP-exposed diabetic mice compared to diabetic mice exposed to saline or DEP-exposed non-diabetic mice. The in vitro addition of DEP (0.25-1 μg/ml) to untreated mouse blood significantly and dose-dependently induced in vitro platelet aggregation, and these effects were exacerbated in blood of diabetic mice.Conclusion: This study has shown that systemic and coagulation events are aggravated by type 1 diabetes in mice, acutely exposed to DEP and has described the possible mechanisms for these actions that may also be relevant to the exacerbation of cardiovascular morbidity accompanying particulate air pollution in diabetic patients.",
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N2 - Background: Epidemiological evidence indicates that diabetic patients have increased susceptibility to adverse cardiovascular outcomes related to acute increases in exposures to particulate air pollution. However, mechanisms underlying these effects remain unclear.Methods: To evaluate the possible mechanisms underlying these actions, we assessed the systemic effects of diesel exhaust particles (DEP) in control mice, and mice with streptozotocin-induced type 1 diabetes. Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4 mg/kg) or saline, and several cardiovascular endpoints were measured 24 h thereafter.Results: DEP caused leukocytosis and a significant increase in plasma C-reactive protein and 8-isoprostane concentrations in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. The arterial PO2 as well as the number of platelets and the thrombotic occlusion time in pial arterioles assessed in vivo were significantly decreased following the i.t. instillation of DEP in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. Both alanine aminotransferase and aspartate transaminase activities, as well as the plasma concentrations of plasminogen activator inhibitor and von Willebrand factor were significantly increased in DEP-exposed diabetic mice compared to diabetic mice exposed to saline or DEP-exposed non-diabetic mice. The in vitro addition of DEP (0.25-1 μg/ml) to untreated mouse blood significantly and dose-dependently induced in vitro platelet aggregation, and these effects were exacerbated in blood of diabetic mice.Conclusion: This study has shown that systemic and coagulation events are aggravated by type 1 diabetes in mice, acutely exposed to DEP and has described the possible mechanisms for these actions that may also be relevant to the exacerbation of cardiovascular morbidity accompanying particulate air pollution in diabetic patients.

AB - Background: Epidemiological evidence indicates that diabetic patients have increased susceptibility to adverse cardiovascular outcomes related to acute increases in exposures to particulate air pollution. However, mechanisms underlying these effects remain unclear.Methods: To evaluate the possible mechanisms underlying these actions, we assessed the systemic effects of diesel exhaust particles (DEP) in control mice, and mice with streptozotocin-induced type 1 diabetes. Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4 mg/kg) or saline, and several cardiovascular endpoints were measured 24 h thereafter.Results: DEP caused leukocytosis and a significant increase in plasma C-reactive protein and 8-isoprostane concentrations in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. The arterial PO2 as well as the number of platelets and the thrombotic occlusion time in pial arterioles assessed in vivo were significantly decreased following the i.t. instillation of DEP in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. Both alanine aminotransferase and aspartate transaminase activities, as well as the plasma concentrations of plasminogen activator inhibitor and von Willebrand factor were significantly increased in DEP-exposed diabetic mice compared to diabetic mice exposed to saline or DEP-exposed non-diabetic mice. The in vitro addition of DEP (0.25-1 μg/ml) to untreated mouse blood significantly and dose-dependently induced in vitro platelet aggregation, and these effects were exacerbated in blood of diabetic mice.Conclusion: This study has shown that systemic and coagulation events are aggravated by type 1 diabetes in mice, acutely exposed to DEP and has described the possible mechanisms for these actions that may also be relevant to the exacerbation of cardiovascular morbidity accompanying particulate air pollution in diabetic patients.

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KW - Diesel exhaust particles

KW - Mice

KW - Platelet aggregation

KW - Streptozotocin

KW - Thrombosis

KW - Type 1 diabetes

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