In vivo assessment of genotoxic, antigenotoxic and anticarcinogenic activities of Solanum lycocarpum fruits glycoalkaloidic extract

The fruits of Solanum lycocarpum, known as wolf-fruit, are used in folk medicine, and because of that we have evaluated both the genotoxic potential of its glycoalkaloidic extract (SL) and its influence on the genotoxicity induced by methyl methanesulfonate. Furthermore, the potential blocking effect of SL intake in the initial stage of colon carcinogenesis in Wistar rats was investigated in a short-term (4-week) bioassay using aberrant crypt foci (ACF) as biomarker. The genotoxic potential was evaluated using the Swiss mice peripheral blood micronucleus test. The animals were treated with different doses of SL (15, 30 and 60 mg/kg b.w.) for 14 days, and the peripheral blood samples were collected at 48 h, 7 days and 14 days after starting the treatment. For antigenotoxicity assessment, MMS was administered on the 14 th day, and after 24 h the harvesting of bone marrow and liver cells was performed, for the micronucleus and comet assays, respectively. In the ACF assay, male Wistar rats were given four subcutaneous injections of the carcinogen 1,2-dimethylhydrazine (DMH, 40 mg/kg b.w.), twice a week, during two weeks to induce ACF. The treatment with SL (15, 30 and 60 mg/kg b.w.) was given for four weeks during and after carcinogen treatment to investigate the potential beneficial effects of SL on DMH-induced ACF. The results demonstrated that SL was not genotoxic in the mouse micronucleus test. In animals treated with SL and MMS, the frequencies of micronucleus and extensions of DNA damage were significantly reduced in comparison with the animals receiving only MMS. Regarding the ACF assay, SL significantly reduced the frequency of ACF induced by DMH.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Frequencies of micronucleated polychromatic erytrocytes (MNPCEs) and polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) obtained from bone marrow of Swiss mice after treatment with SL and/or MMS, and their respective controls.

<p>MMS: methyl methanesulfonate (40 mg/kg b.w.); SL: <i>Solanum lycocarpum</i> fruits glicoalkaloid extract.</p>a<p>Significantly different of the control group (<i>P</i><0.05).</p>b<p>Significantly different of the MMS group (<i>P</i><0.05).</p><p>12000 polychromatic erythrocytes were analyzed per treatment.</p><p>Frequencies of micronucleated polychromatic erytrocytes (MNPCEs) and polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) obtained from bone marrow of Swiss mice after treatment with SL and/or MMS, and their respective controls.</p

Mean percentage of DNA damage by the comet assay and cell viability by Trypan blue exclusion dye method in the liver cells of Swiss mice after treatment with SL and/or MMS, and their respectives controls.

<p>MMS: methyl methanesulfonate (40 mg/kg b.w.); SL: <i>Solanum lycocarpum</i> fruits glicoalkaloid extract.</p>a<p>Significantly different of the control group (<i>P</i><0.05).</p>b<p>Significantly different of the MMS group (<i>P</i><0.05).</p><p>600 nucleoids were analyzed per treatment.</p><p>Mean percentage of DNA damage by the comet assay and cell viability by Trypan blue exclusion dye method in the liver cells of Swiss mice after treatment with SL and/or MMS, and their respectives controls.</p

Photomicrograph of methylene blue-stained, whole-mount preparations of colon from Wistar rats treated with DMH with ACF contaning one (A) and five (B) aberrant crypts/focus.

<p>Photomicrograph of methylene blue-stained, whole-mount preparations of colon from Wistar rats treated with DMH with ACF contaning one (A) and five (B) aberrant crypts/focus.</p

Initial body weight, final body weight, body weight gain and water consumption of Swiss mice after treatment for 14 days with SL and/or MMS, and their respective controls.

<p>MMS: methyl methanesulfonate (40 mg/kg b.w.); SL: <i>Solanum lycocarpum</i> fruits glicoalkaloid extract.</p><p>Initial body weight, final body weight, body weight gain and water consumption of Swiss mice after treatment for 14 days with SL and/or MMS, and their respective controls.</p

HPLC chromatogram of the alkaloidic extract of <i>Solanum lycocarpum</i> fruits.

<p>Zorbax-SB (5 µm), 250×4.6 mm column; mobile phase of acetonitrile and phosphate buffer 0.01 M (36.5∶63.5); flow rate of 1.0 mL/min and detection at 200 nm. SLN = Solasonine; SLM = Solamargine.</p

Mean number (± SD) of aberrant crypt foci (ACF) and aberrant crypt in the distal colon of rats in response to SL during and after DMH treatment.

<p>DMH :1,2 dimethylhydrazine (160 mg/kg b.w.); SL: <i>Solanum lycocarpum</i> fruits glicoalkaloid extract.</p>a<p>Significantly different of the DMH group (<i>P</i><0.05).</p><p>300 fields sequential/distal segment of the colon were analyzed per treatment.</p><p>Negative control animals and SL 60 mg/kg b.w. no showed ACF and aberrant crypt.</p><p>Mean number (± SD) of aberrant crypt foci (ACF) and aberrant crypt in the distal colon of rats in response to SL during and after DMH treatment.</p

Núcleos de Ensino da Unesp: artigos 2008

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