Comparison of Pharmacokinetics and Anti-Pulmonary Fibrosis-Related Effects of Sulforaphane and Sulforaphane <i>N</i>-acetylcysteine
Sulforaphane (SFN), belonging to the isothiocyanate family, has received attention owing to its beneficial activities, including chemopreventive and antifibrotic effects. As sulforaphane <i>N</i>-acetylcysteine (SFN-NAC), a major sulforaphane metabolite, has presented similar pharmacolog...
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| Online Access: | https://www.mdpi.com/1999-4923/13/7/958 |
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| author | Eun Suk Son Xiang Fei Jin-Ha Yoon Seung-Yong Seo Han-Joo Maeng Sung Hwan Jeong Yu Chul Kim |
| author_facet | Eun Suk Son Xiang Fei Jin-Ha Yoon Seung-Yong Seo Han-Joo Maeng Sung Hwan Jeong Yu Chul Kim |
| author_sort | Eun Suk Son |
| collection | DOAJ |
| description | Sulforaphane (SFN), belonging to the isothiocyanate family, has received attention owing to its beneficial activities, including chemopreventive and antifibrotic effects. As sulforaphane <i>N</i>-acetylcysteine (SFN-NAC), a major sulforaphane metabolite, has presented similar pharmacological activities to those of SFN, it is crucial to simultaneously analyze the pharmacokinetics and activities of SFN and SFN-NAC, to comprehensively elucidate the efficacy of SFN-containing products. Accordingly, the anti-pulmonary fibrotic effects of SFN and SFN-NAC were assessed, with simultaneous evaluation of permeability, metabolic stability, and in vivo pharmacokinetics. Both SFN and SFN-NAC decreased the levels of transforming growth factor-β1-induced fibronectin, alpha-smooth muscle actin, and collagen, which are major mediators of fibrosis, in MRC-5 fibroblast cells. Regarding pharmacokinetics, SFN and SFN-NAC were metabolically unstable, especially in the plasma. SFN-NAC degraded considerably faster than SFN in plasma, with SFN being formed from SFN-NAC. In rats, SFN and SFN-NAC showed a similar clearance when administered intravenously; however, SFN showed markedly superior absorption when administered orally. Although the plasma SFN-NAC concentration was low owing to poor absorption following oral administration, SFN-NAC was converted to SFN in vivo, as in plasma. Collectively, these data suggest that SFN-NAC could benefit a prodrug formulation strategy, possibly avoiding the gastrointestinal side effects of SFN, and with improved SFN-NAC absorption. |
| first_indexed | 2024-03-10T10:04:10Z |
| format | Article |
| id | doaj.art-fdf18cf82af84320abe1a307ac1c3836 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T10:04:10Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-fdf18cf82af84320abe1a307ac1c38362023-11-22T01:41:41ZengMDPI AGPharmaceutics1999-49232021-06-0113795810.3390/pharmaceutics13070958Comparison of Pharmacokinetics and Anti-Pulmonary Fibrosis-Related Effects of Sulforaphane and Sulforaphane <i>N</i>-acetylcysteineEun Suk Son0Xiang Fei1Jin-Ha Yoon2Seung-Yong Seo3Han-Joo Maeng4Sung Hwan Jeong5Yu Chul Kim6Department of Medicine, Gachon University Gil Medical Center, Incheon 21565, KoreaDepartment of Pharmacy, College of Pharmacy, Gachon University, Incheon 21936, KoreaDepartment of Pharmacy, College of Pharmacy, Gachon University, Incheon 21936, KoreaDepartment of Pharmacy, College of Pharmacy, Gachon University, Incheon 21936, KoreaDepartment of Pharmacy, College of Pharmacy, Gachon University, Incheon 21936, KoreaDepartment of Medicine, Gachon University Gil Medical Center, Incheon 21565, KoreaDepartment of Pharmaceutical Engineering, Inje University, Gimhae 50834, KoreaSulforaphane (SFN), belonging to the isothiocyanate family, has received attention owing to its beneficial activities, including chemopreventive and antifibrotic effects. As sulforaphane <i>N</i>-acetylcysteine (SFN-NAC), a major sulforaphane metabolite, has presented similar pharmacological activities to those of SFN, it is crucial to simultaneously analyze the pharmacokinetics and activities of SFN and SFN-NAC, to comprehensively elucidate the efficacy of SFN-containing products. Accordingly, the anti-pulmonary fibrotic effects of SFN and SFN-NAC were assessed, with simultaneous evaluation of permeability, metabolic stability, and in vivo pharmacokinetics. Both SFN and SFN-NAC decreased the levels of transforming growth factor-β1-induced fibronectin, alpha-smooth muscle actin, and collagen, which are major mediators of fibrosis, in MRC-5 fibroblast cells. Regarding pharmacokinetics, SFN and SFN-NAC were metabolically unstable, especially in the plasma. SFN-NAC degraded considerably faster than SFN in plasma, with SFN being formed from SFN-NAC. In rats, SFN and SFN-NAC showed a similar clearance when administered intravenously; however, SFN showed markedly superior absorption when administered orally. Although the plasma SFN-NAC concentration was low owing to poor absorption following oral administration, SFN-NAC was converted to SFN in vivo, as in plasma. Collectively, these data suggest that SFN-NAC could benefit a prodrug formulation strategy, possibly avoiding the gastrointestinal side effects of SFN, and with improved SFN-NAC absorption.https://www.mdpi.com/1999-4923/13/7/958sulforaphanesulforaphane <i>N</i>-acetylcysteineanti-pulmonary fibrosis effectpharmacokineticsmetabolic stability |
| spellingShingle | Eun Suk Son Xiang Fei Jin-Ha Yoon Seung-Yong Seo Han-Joo Maeng Sung Hwan Jeong Yu Chul Kim Comparison of Pharmacokinetics and Anti-Pulmonary Fibrosis-Related Effects of Sulforaphane and Sulforaphane <i>N</i>-acetylcysteine Pharmaceutics sulforaphane sulforaphane <i>N</i>-acetylcysteine anti-pulmonary fibrosis effect pharmacokinetics metabolic stability |
| title | Comparison of Pharmacokinetics and Anti-Pulmonary Fibrosis-Related Effects of Sulforaphane and Sulforaphane <i>N</i>-acetylcysteine |
| title_full | Comparison of Pharmacokinetics and Anti-Pulmonary Fibrosis-Related Effects of Sulforaphane and Sulforaphane <i>N</i>-acetylcysteine |
| title_fullStr | Comparison of Pharmacokinetics and Anti-Pulmonary Fibrosis-Related Effects of Sulforaphane and Sulforaphane <i>N</i>-acetylcysteine |
| title_full_unstemmed | Comparison of Pharmacokinetics and Anti-Pulmonary Fibrosis-Related Effects of Sulforaphane and Sulforaphane <i>N</i>-acetylcysteine |
| title_short | Comparison of Pharmacokinetics and Anti-Pulmonary Fibrosis-Related Effects of Sulforaphane and Sulforaphane <i>N</i>-acetylcysteine |
| title_sort | comparison of pharmacokinetics and anti pulmonary fibrosis related effects of sulforaphane and sulforaphane i n i acetylcysteine |
| topic | sulforaphane sulforaphane <i>N</i>-acetylcysteine anti-pulmonary fibrosis effect pharmacokinetics metabolic stability |
| url | https://www.mdpi.com/1999-4923/13/7/958 |
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