Green tea extract inhibits paraquat-induced pulmonary fibrosis by suppression of oxidative stress and endothelin-l expression.
Paraquat-induced pulmonary fibrosis involves two factors, direct injury by oxygen free radicals and indirect injury by inflammatory cells and fibroblasts. Endothelin-1 (ET-1) has been shown to act as a mediator of pulmonary fibrosis, and its formation increases during oxidative stress. We investigated whether green tea extract (GTE), which has antioxidant properties, inhibits paraquat-induced pulmonary fibrosis and whether ET-1 is involved in this process. Paraquat (0.3 mg/kg) was instilled into the right lungs of rats, following which the rats were either not further treated (Group P, n = 7), or they were administered 1% GTE mixed with feed (Group PG; n = 7) or the ET(A) receptor antagonist ZD2574 (10 mg/kg through gavage; Group PZ; n = 7) for two weeks. As control, we used rats instilled with saline (Group N; n = 6). Two weeks after paraquat instillation, we assayed the degree of pulmonary fibrosis by light microscopic morphometry and hydroxyproline content; lipid peroxidation as a marker of oxidative stresses by measurement of malondialdehyde (MDA); ET-1 by immunohistochemistry; and prepro-ET-1 mRNA expression by reverse transcription-polymerase chain reaction. Compared with Group N, significant pulmonary fibrosis was observed in Group P, accompanied by increases in MDA, ET-1, and prepro-ET-1 mRNA expression. Compared with Group P, Group PG showed significant decreases in pulmonary fibrosis, along with decreases in MDA, ET-1, and prepro-ET-1 mRNA expression. We also observed significant decreases in pulmonary fibrosis in Group PZ compared with Group P. These findings suggest that GTE inhibits paraquat-induced pulmonary fibrosis by suppression of oxidative stress and ET-1 expression.
Kim
Hak-Ryul
HR
Department of Internal Medicine, College of Medicine, Wonkwang University, Iksan, Republic of Korea.
Park
Byung-Kyu
BK
Oh
Yeon-Mok
YM
Lee
Yun-Song
YS
Lee
Dong-Soon
DS
Kim
Hyun-Kuk
HK
Kim
Joo-Young
JY
Shim
Tae-Sun
TS
Lee
Sang-Do
SD
D000818:Animals; D028241:Camellia sinensis; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D006540:Herbicides / Q000633:toxicity; D007150:Immunohistochemistry; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000633:toxicity; D010936:Plant Extracts / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D012313:RNA / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D019332:Endothelin-1; D006540:Herbicides; D010936:Plant Extracts; C465546:green tea extract AR25; D008315:Malondialdehyde; D012313:RNA; D010269:Paraquat