Protective effects of the bioactive natural product N-trans-Caffeoyldopamine on hepatotoxicity induced by isoniazid and rifampicin

https://doi.org/10.1016/j.bmcl.2015.09.003Get rights and content

Abstract

In our searching for novel antioxidants from natural sources, N-trans-Caffeoyldopamine which was from natural product was found to be a potential compound for its remarkable antioxidant activity. Isoniazid (INH) and Rifampicin (RFP) is widely used for the treatment of Tuberculosis (TB) as the first line drugs, have been known to be potentially hepatotoxic and may lead to drug-induced liver injury.

Oxidative stress has been regarded as the major mechanism of the hepatotoxicity. Therefore, in this study, the possible protective effects of N-trans-Caffeoyldopamine was investigated in the hepatotoxicity caused by INH and RFP in rats. Results showed that serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and hepatic malondialdehyde (MDA) content were reduced dramatically, and hepatic superoxide dismutase (SOD) activity and glutathione (GSH) content were restored remarkably by N-trans-Caffeoyldopamine co-administration, as compared to the INH–RFP treated rats (p <0.01). Moreover, the histopathological damage of liver and the number of apoptotic hepatocytes were also significantly ameliorated by the treatment. It is therefore suggested that N-trans-Caffeoyldopamine can provide a definite protective effect against acute hepatic injury caused by INH and RFP in rats, which may mainly be associated with its antioxidative effect. Mechanisms studies indicated that it inhibited the lipid peroxidation through the cytochrome P450 2E1 (CYP2E1) downregulation.

Section snippets

Acknowledgments

This study was supported by the Fundamental Research Funds for the Central Universities of China (lzujbky-2014-150, lzujbky-2015-57, lzujbky-2015-61), as well as the Foundation of The Health Industry research project of Gansu province (GWGL2014-45).

References and notes (16)

  • M. Shiino et al.

    Bioorg. Chem.

    (2003)
  • F.F. Yin et al.

    J. Pharm. Sci.

    (2015)
    V. Pérez Alvarez et al.

    J. Appl. Toxicol.

    (2001)
  • M. Tarasankar et al.

    Int. J. Pharm. Pharm. Sci.

    (2012)
    E. Sude et al.

    Nutr. Metab.

    (2008)
  • K. Sano et al.

    Antimicrob. Agents Chemother.

    (2004)
    A. Fagerlund et al.

    Food Chem.

    (2009)
    E. Yakup et al.

    Pediatr. Int.

    (2010)
    S. Attri et al.

    Hum. Exp. Toxicol.

    (2010)
  • T. Toshiyuki et al.

    Bioorg. Med. Chem. Lett.

    (2011)
  • C.G. Fraga et al.

    J. Clin. Biochem. Nutr.

    (2010)
    J.B. Park

    J. Agric. Food Chem.

    (2007)
  • Zh.R. Wu et al.

    Food Chem.

    (2012)
  • K. Fujioka et al.

    J. Agric. Food Chem.

    (2006)
    F. Aladedunye et al.

    Food Chem.

    (2012)
There are more references available in the full text version of this article.

Cited by (18)

  • Grape seed procyanidin extract ameliorates lead-induced liver injury via miRNA153 and AKT/GSK-3β/Fyn-mediated Nrf2 activation

    2018, Journal of Nutritional Biochemistry
    Citation Excerpt :

    Surprisingly, we have not observed significant changes in the expression of CYP2E1, as an origin of increased oxidative stress, in the livers of PbAc-treated rats. This result was inconsistent with many studies reporting increased CYP2E1 expression during hepatotoxicity [40–42]. The presence of CYP2E1 at basal levels may have been sufficient to induce hepatic damage in our experiments, but whether CYP2E1 plays a role in PbAc-induced hepatotoxicity warrants further investigation.

  • Metallothionein protects against isoniazid-induced liver injury through the inhibition of CYP2E1-dependent oxidative and nitrosative impairment in mice

    2017, Food and Chemical Toxicology
    Citation Excerpt :

    It has been revealed that inhibition of CYP2E1 activity can ameliorate INH/RFP liver toxicity (Shih et al., 2013a, 2013b). And several agents can exert hepatoprotective effects against INH hepatotoxicity by reducing the free radical generation and lipid peroxidation via the suppression of hepatic CYP2E1 activity or down-regulation of CYP2E1 expression (Yue et al., 2009; Palanisamy and Manian, 2012; Wu et al., 2015). Conversely, enhanced induction of CYP2E1 exacerbated INH hepatotoxicity in human hepatocytes was also observed (Shen et al., 2008).

  • Medical plant extracts and natural compounds with a hepatoprotective effect against damage caused by antitubercular drugs: A review

    2016, Asian Pacific Journal of Tropical Medicine
    Citation Excerpt :

    It is therefore, suggested that N-trans-Caffeoyldopamine can provide a definite protective effect against acute hepatic injury caused by INH/RIF in rats, which may mainly be associated with its antioxidative effect. This compound inhibited LPO through the CYP4502E1 down-regulation [96]. On the other hand, the triterpenes Oleanolic Acid (OA, 3-β-hydroxy-olea-12-en-28-oic acid) and Ursolic Acid (UA, 3-β-hydroxyurs-12-en-28-oic acid) possess an important hepatoprotective effect against the liver damage caused by EtOH, CCl4, d-galactosamine, acetaminophen, cadmium, bromobenzene, phalloidin, thioacetamide and other hepatotoxic substances [97–100].

  • Transcriptome profiling and pathway analysis of hepatotoxicity induced by tris (2-ethylhexyl) trimellitate (TOTM) in mice

    2016, Environmental Toxicology and Pharmacology
    Citation Excerpt :

    Both enzymes are responsible for not only drug metabolism but also the catalysis of many poisons and carcinogens (Gonzalez, 2005; Oesch-Bartlomowicz and Oesch, 2005). Some chemical drug commonly used in clinic, such as acetaminophen, isoniazid and rifampicin, induced obvious hepatotoxicity via upregulating the cytochrome P450, mainly CYP2E1 and CYP1A2 (Hassan et al., 2015; Jing et al., 2015; Wu et al., 2015), while natural antioxidants can target these defective genes to alleviate the drug-induced poisoning (Al-Sayed and Abdel-Daim, 2014; Fan et al., 2014; Wang et al., 2014; Nguyen et al., 2015). In this study, three main pathways (Drug metabolism – cytochrome P450, metabolism of xenobiotics by cytochrome P450 and chemical carcinogenesis) were enriched by KEGG analysis.

View all citing articles on Scopus
View full text