Comparison of Pharmacokinetics and Anti-Pulmonary Fibrosis-Related Effects of Sulforaphane and Sulforaphane N-acetylcysteine

• Published in: Pharmaceutics Vol. 13; no. 7; p. 958
• Main Authors: Son, Eun Suk, Fei, Xiang, Yoon, Jin-Ha, Seo, Seung-Yong, Maeng, Han-Joo, Jeong, Sung Hwan, Kim, Yu Chul
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 25.06.2021; MDPI
• Subjects: anti-pulmonary fibrosis effect; Antibodies; Bioavailability; Cancer; Collagen; Drug dosages; Enzymes; Experiments; Fibroblasts; Growth factors; Liver; metabolic stability; Metabolism; Metabolites; Permeability; Pharmacokinetics; Plasma; Proteins; Pulmonary fibrosis; Reagents; sulforaphane; sulforaphane N-acetylcysteine; United States > US; Japan
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics13070958

Sulforaphane (SFN), belonging to the isothiocyanate family, has received attention owing to its beneficial activities, including chemopreventive and antifibrotic effects. As sulforaphane N-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.