S-allyl cysteine attenuated CCl4-induced oxidative stress and pulmonary fibrosis in rats.
This study examined effects of S-allyl cysteine (SAC) on carbon tetrachloride (CCl4)-induced interstitial pulmonary fibrosis in Wistar rats. CCl4 (0.5 ml/kg) was intraperitoneally injected into rats twice a week for 8 weeks, and SAC (50, 100, or 200 mg/kg), N-acetyl cysteine (NAC, 200 or 600 mg/kg), or L-cysteine (CYS, 600 mg/kg) were orally administrated to rats everyday for 8 weeks. SAC significantly reduced the increases of transforming growth factor beta, lipid peroxides, AST, and ALT in plasma, induced by CCl4. Although CCl4 is mainly metabolized by hepatic cytochrome P450, CCl4 induced systemic inflammation and some organ fibrosis. SAC dose-dependently and significantly attenuated CCl4-induced systemic inflammation and fibrosis of lung. SAC also inhibited the decrease of thiol levels, the increase of inducible nitric oxide synthase expression, the infiltration of leukocytes, and the generation of reactive oxygen species in lungs. Although NAC and CYS attenuated CCl4-induced pulmonary inflammation and fibrosis, the order of preventive potency was SAC > NAC > CYS according to their applied doses. These results indicate that SAC is more effective than other cysteine compounds in reducing CCl4-induced lung injury, and might be useful in prevention of interstitial pulmonary fibrosis.
Mizuguchi
Shinjiro
S
Department of Cardiovascular Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan. m1381731@med.osaka-cu.ac.jp
Takemura
Shigekazu
S
Minamiyama
Yukiko
Y
Kodai
Shintaro
S
Tsukioka
Takuma
T
Inoue
Kiyotoshi
K
Okada
Shigeru
S
Suehiro
Shigefumi
S
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004792:Enzyme Precursors / Q000032:analysis; D005978:Glutathione / Q000032:analysis; D006909:Hydroxyproline / Q000032:analysis; D008099:Liver / Q000473:pathology; D008168:Lung / Q000737:chemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D009569:Nitric Oxide / Q000652:urine; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000097:blood; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1
D004792:Enzyme Precursors; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; C065299:S-allylcysteine; D002251:Carbon Tetrachloride; D052247:Nitric Oxide Synthase Type II; D020780:Matrix Metalloproteinase 9; D005978:Glutathione; D003545:Cysteine; D006909:Hydroxyproline