Green Tea Extract Inhibits Paraquat-Induced Pulmonary Fibrosis by Suppression of Oxidative Stress and Endothelin-l Expression

Abstract

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.

The Preventive Role of Gemfibrozil on Bleomycin-Induced Lung Injury and Fibrosis in Rats

“…In addition, it was shown that curcumin, as an antioxidant compound, was inhibited by the development pulmonary fibrosis, which is a good reason for its use (5). Green tea extract administration is effective in pulmonary fibrosis by reduction of MDA and hydroxyproline levels and endothelin expression (39). In an animal model of liver fibrosis, it has been recognized that decreased PPAR-α and increased TGF-β expressions was associated with development of hepatic fibrosis (40).…”

Efektivitas Ekstrak Teh Hijau, Kulit Manggis Dan Biji Pinang Pada Penanganan Keracunan Paraquat Pada Kambing

“…Pemanfaatan teh hijau, kulit manggis, dan biji pinang untuk intoksikasi paraquat telah dilakukan dan menunjukkan hasil positif (Higuchi et al 2003;Kim et al 2006;Tanaka 2007). Namunpemanfaatan teh hijau, kulit manggis dan biji pinang untuk intoksikasi (keracunan) paraquat pada ternak ruminansia khususnya di Indonesia belum pernah dilakukan.…”

“…Pada keracunan paraquat,EGCG berfungsi menghambat produksi microsomal malondialdehyde (MDA) dalam hati,mereduksi Fe yang berlebihan pada Fe-lipid peroxidation sebagai efek paraquat sehingga mengurangi kerusakan organ dan membersihkan radikal DMPO-OOH spin dalam microsomeparaquat system (Higuchi et al 2003). Teh hijau dapat menurunkan fibrosis paruparu pada tikus dengan menekan proses stres oksidatif dan ekspresi endothelin-1 (Kim et al 2006).…”

“…Hasil penelitian secara in vivo menunjukkan ekstrak teh hijau, kulit manggis dan biji pinang dapat digunakan sebagai obat pada kasus keracunan paraquat pada kambing. Di Mesir dan Korea teh hijau telah diuji dan terbukti mengurangi efek toksik paraquat pada tikus (El-Sayed dan Rizk 2009; Kim et al 2006). Gambar 5.…”

Protective effect of 4,4'-diaminodiphenylsulfone against paraquat-induced mouse lung injury

“…In addition, endothelin-1 (ET-1) has been reported to participate in the pathogenesis of bleomycin-induced and idiopathic pulmonary fibrosis (Kähler et al, 2000;Kaehler et al, 2002). Furthermore, lung ET-1 expression was shown to be upregulated during PQ-induced pulmonary fibrosis (Kim et al, 2006).…”