Pulmonary effects of inhaled limonene ozone reaction products in elderly rats.
d-Limonene is an unsaturated volatile organic chemical found in cleaning products, air fresheners and soaps. It is oxidized by ozone to secondary organic aerosols consisting of aldehydes, acids, oxidants and fine and ultra fine particles. The lung irritant effects of these limonene ozone reaction products (LOP) were investigated. Female F344 rats (2- and 18-month-old) were exposed for 3 h to air or LOP formed by reacting 6 ppm d-limonene and 0.8 ppm ozone. BAL fluid, lung tissue and cells were analyzed 0 h and 20 h later. Inhalation of LOP increased TNF-alpha, cyclooxygenase-2, and superoxide dismutase in alveolar macrophages (AM) and Type II cells. Responses of older animals were attenuated when compared to younger animals. LOP also decreased p38 MAP kinase in AM from both younger and older animals. In contrast, while LOP increased p44/42 MAP kinase in AM from younger rats, expression decreased in AM and Type II cells from older animals. NF-kappaB and C/EBP activity also increased in AM from younger animals following LOP exposure but decreased or was unaffected in Type II cells. Whereas in younger animals LOP caused endothelial cell hypertrophy, perivascular and pleural edema and thickening of alveolar septal walls, in lungs from older animals, patchy accumulation of fluid within septal walls in alveolar sacs and subtle pleural edema were noted. LOP are pulmonary irritants inducing distinct inflammatory responses in younger and older animals. This may contribute to the differential sensitivity of these populations to pulmonary irritants.
Sunil
Vasanthi R
VR
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08854, USA. sunilvr@eohsi.rutgers.edu
Laumbach
Robert J
RJ
Patel
Kinal J
KJ
Turpin
Barbara J
BJ
Lim
Ho-Jin
HJ
Kipen
Howard M
HM
Laskin
Jeffrey D
JD
Laskin
Debra L
DL
D000280:Administration, Inhalation; D000336:Aerosols; D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D053138:Cyclohexenes / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D000077222:Limonene; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008962:Models, Theoretical; D010126:Ozone / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D011485:Protein Binding / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013047:Specific Pathogen-Free Organisms; D013482:Superoxide Dismutase / Q000378:metabolism; D013729:Terpenes / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D014157:Transcription Factors / Q000378:metabolism
D000336:Aerosols; D000975:Antioxidants; D053138:Cyclohexenes; D018836:Inflammation Mediators; D013729:Terpenes; D014157:Transcription Factors; D010126:Ozone; D000077222:Limonene; D013482:Superoxide Dismutase; D020928:Mitogen-Activated Protein Kinases