Impact experimental type 1 diabetes mellitus coagulation vulnerability mice exposed diesel exhaust | ANMA – Associazione Nazionale del Medico Competente e d'Azienda

Particle and Fibre Toxicology. Vol. 10, Iss. 12, 14, 15, 16, 17, April 2013

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 and Badreldin H Ali

Riassunto

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.

Commento

Vari studi epidemiologici hanno dimostrato, negli ultimi anni, la presenza di un collegamento tra il particolato atmosferico urbano ed una maggiore morbilità e mortalità per patologie cardiovascolari, anche a basse concentrazioni di inquinanti atmosferici. Una caratteristica importante di questa correlazione è rappresentata dal fatto che gli effetti avversi del particolato atmosferico sembrano essere più marcati nelle persone con patologie cardiovascolari già esistenti o con fattori di rischio come il diabete mellito. In relazione al diabete, è stato dimostrato che l'esposizione cronica a PM2.5 aggrava la resistenza all'insulina ed aumenta l'infiammazione nel tessuto adiposo. Lo scopo del presente studio è stato quello di quantificare gli effetti dell'esposizione al particolato atmosferico in cavie da laboratorio, con diabete di tipo 1, sui principali parametri cardiovascolari quali la trombosi arteriolare, l'aggregazione piastrinica, i marcatori di infiammazione, lo stress ossidativo e la fibrinolisi.

Keywords

Air pollution, Diesel exhaust particles, Mice, Platelet aggregation, Streptozotocin, thrombosis, Type 1 diabetes

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