Sesamol attenuates bleomycin-induced pulmonary toxicity and fibrosis in experimental animals

被引:2
作者
Kaushik, Swati [1 ]
Bhargava, Poorva [1 ]
Sharma, Jatin [1 ]
Arava, Sudheer [2 ]
Nag, Tapas C. [3 ]
Arya, Dharamvir S. [1 ]
Bhatia, Jagriti [1 ,4 ]
机构
[1] All India Inst Med Sci, Dept Pharmacol, Cardiovasc Res Lab, New Delhi, India
[2] All India Inst Med Sci, Dept Pathol, New Delhi, India
[3] All India Inst Med Sci, Dept Anat, New Delhi, India
[4] All India Inst Med Sci, Dept Pharmacol, Cardiovasc Res Lab, New Delhi 110029, India
关键词
bleomycin; pulmonary fibrosis; pulmonary toxicity; sesamol; TGF-beta; NECROSIS-FACTOR-ALPHA; ACTIVATED PROTEIN-KINASE; TGF-BETA; OXIDATIVE STRESS; TNF-ALPHA; LUNG; MECHANISMS; APOPTOSIS; CELLS; INTERLEUKIN-6;
D O I
10.1002/jbt.23472
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Sesamol, a lignan obtained from roasted seeds of Sesamum indicum, has high antioxidant and anti-inflammatory activity. In this study, we have investigated the effect of sesamol on Bleomycin (BLM) induced pulmonary toxicity as well as fibrosis in Wistar rats. Lung toxicity was induced by administration of BLM, 0.015U/g ip, twice weekly for 28 days whereas lung fibrosis was induced by BLM, 0.015 U/g ip, every 5th day for 49 days. Sesamol administration was started 7 days before first dose of BLM in both the models. It was observed that sesamol 50mg/kg most effectively attenuated pulmonary toxicity by reducing oxidative stress, inflammation and apoptosis. This dose was further evaluated for its anti-fibrotic effect. It was observed that there was a significant reduction in fibrosis. Lung collagen content was markedly reduced. Furthermore, expression of pro-fibrotic proteins, TGF-beta/SMAD and alpha-SMA, was reduced and that of anti-fibrotic protein, AMPK, was markedly increased. Even though the combination of sesamol with pirfenidone exhibited no additional protection than either drug alone, it is evident from our study that our test drug, sesamol is comparable in efficacy to pirfenidone. Thus, sesamol has promising therapeutic potential in treatment of pulmonary toxicity and fibrosis.
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页数:18
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