Protective Effects of Dietary Capsaicin on the Initiation Step of a Two-Stage Hepatocarcinogenesis Rat Model

Abstract

Capsaicin (CPS), an ingredient of Capsicum plants, has anti-inflammatory, antioxidant and antitumoral properties. The mechanisms of CPS on hepatocarcinogenesis preclinical bioassays are not described. Thus, the protective effects CPS were evaluated in the early stages of chemically-induced hepatocarcinogenesis. Male Wistar rats received diet containing 0.01% or 0.02% CPS for 3 weeks. Afterwards, animals received a dose of hepatocarcinogen diethylnitrosamine (DEN, 100 mg/kg body weight). From weeks 4–12, groups had their diet replaced by a 0.05% phenobarbital supplemented one to promote DEN-induced preneoplastic lesions. Animals were euthanized 24 h after DEN administration (n = 5/group) or at week 12 (n = 9/group). The estimated CPS intake in rats resembled human consumption. At the end of week 3, dietary 0.02% CPS attenuated DEN-induced oxidative damage and, consequently, hepatocyte necrosis by reducing serum alanine aminotransferase levels, liver CD68-positive macrophages, lipid peroxidation, while increasing antioxidant glutathione system. Additionally, 0.02% CPS upregulated vanilloid Trpv1 receptor and anti-inflammatory epoxygenase Cyp2j4 genes in the liver. Ultimately, previous 0.02% CPS intake decreased the number of GST-P-positive preneoplastic lesions at week 12. Thus, CPS attenuated preneoplastic lesion development, primarily by diminishing DEN-induced oxidative liver injury. Findings indicate that CPS is a promising chemopreventive agent when administered after and during the early stages of hepatocarcinogenesis.

Acknowledgments

The authors to thank Dr. Isamery Machado de Sarmiento and Wismar Sarmiento for their assistance in the writing the manuscript. Luis M. Sarmiento-Machado joined ICSB/UNESP program (ISB, 42052/2017).

Disclosure statement

The authors report no conflict of interest.

Author Contributions

L. M. S. Machado, G. R. Romualdo, M. B. Tablas and J. R. Zapaterini contributed to data acquisition, analysis, interpretation and article draft. L. F. Barbisan, A. A. H. Fernandes and F. S. Moreno authorships were based on conception, design, and revision of the manuscript. All authors approved the final version of the manuscript.

Additional information

Funding

Guilherme R. Romualdo, Joyce R. Zapaterini and Mariana B. Tablas were recipients of fellowships from the São Paulo Research Foundation (FAPESP #2016/12015-0 and #2018/19432-1) and Coordination for the Improvement of Higher Education Personnel (CAPES), respectively. Luis F. Barbisan was recipient of a researcher fellowship from National Council for Scientific and Technological Development (CNPq, #304128/2015-5).