Styrax camporum, a typical species of the Brazilian cerrado, attenuates DNA damage, preneoplastic lesions and oxidative stress in experimental rat colon carcinogenesis

ABSTRACT

Styrax camporum Pohl, a typical species from the Brazilian cerrado, commonly known as “benjoeiro”, is used to treat gastroduodenal diseases. In previous studies carried out by our research group, hydroalcoholic extract of S. camporum stems (SCHE) exhibited antigenotoxic and antiproliferative effects. For a comparative analysis of the chemopreventive effect of SCHE, the aim of this study was to investigate the influence of SCHE against carcinogen 1,2-dimethylhydrazine (DMH)-induced DNA damage and pre-neoplastic lesions in Wistar rat colon. Animals were treated orally with SCHE at 250, 500 or 1000 mg/kg body weight in conjunction with a subcutaneous injection of DMH. DNA damage was assessed using the comet assay while tpre-neoplastic lesions by aberrant crypt foci (ACF) assay. The following hepatic oxidative stress markers were determined including activities of catalase (CAT) and glutathione S-transferase (GST) as well as levels of reduced glutathione (GSH) and malondialdehyde (MDA). Treatment with SCHE was not genotoxic or carcinogenic at the highest dose tested (1000 mg/kg b.w.). The extract effectively inhibited DNA damage and pre-neoplastic lesions induced by DMH administration at all concentrations tested. Measurement of CAT, and GST activities and levels of GSH showed that SCHE did not reduce oxidative processes. In contrast, treatment with SCHE (1000 mg/kg b.w.) decreased liver MDA levels. Taken together, these findings suggested the chemopreventive effect attributed to SCHE in colon carcinogenesis, may be related to its capacity to inhibit DNA damage as well as an antioxidant action associated with its chemical constituents egonol and homoegonol.

KEYWORDS:

• Styrax camporum
• comet assay
• oxidative stress
• aberrant crypt foci
• chemoprevention

List of abbreviations

AC - aberrant crypts; ACF - aberrant crypt foci; AOM – azoxymethane; B16F10 - murine melanoma; CAT – catalase; CDNB - 1-chlorine,2,4-dinitrobenzene; COX 1 - cyclooxygenase enzyme 1; COX 2 - cyclooxygenase enzyme 2; CRC - Colorectal cancer; DNA - deoxyribonucleic acid; DMH - 1,2-dimethylhydrazine; DNTB - 5,5ʹ-dithio-bis-2-nitrobenzoic; EDTA - ethylenediaminetetraacetic acid; GST - glutathione S-transferase; GSH - reduced glutathione; HeLa - human cervical adenocarcinoma; HepG2 - human hepatocellular carcinoma; H3P04 - phosphoric acid; H2O2 - hydrogen peroxide; iNOS - nitric oxide synthase; KCL - potassium chloride; MAM – methylazoxymethanol; MDA – malondialdehyde; MCF-7 - human breast adenocarcinoma; MO59J - human glioblastoma; NF-Kb - actor nuclear kappa B; NSAIDs - non-steroidal anti-inflammatory drugs; PBS - phosphate-buffered salt solution; RNA - ribonucleic acid; SCHE - hydroalcoholic extract of S. camporum stems; TCA - trichloroacetic acid; TBA - 2-thiobarbituric acid.

Acknowledgments

The authors are also grateful to the National Council for Scientific and Technological Development (CNPq, Brazil) for granting fellowships.

Disclosure statement

The authors declare that there is no conflict of interest

Additional information

Funding

This work was supported by the state funding agency São Paulo Research Foundation (FAPESP, Brazil; grant #2013/13903-9). P.F. Oliveira thanks FAPESP for the Doctoral scholarship (grant #2011/21310-2);São Paulo Research Foundation [grant #2011/21310-2,grant #2013/13903-9]