Natural substances offer interesting bioactivity patterns including antiproliferative, antioxidant or cytotoxic effects. However, the safety profile of many of them has not been extensively determined. In this study, the cytotoxic effect of Aeruginosin-865, resveratrol and capsaicin at different concentrations was tested on normal mouse cells (NIH/3T3) and tumour fibroblasts (WEHI-13VAR) as well as on liver-and kidney-derived cells from fallow deer. A lactate dehydrogenase cytotoxicity assay kit was used to measure cell death in response to treatment with the test substances. It was found that NIH/3T3 cells tolerated Aeruginosin-865 (10-200 M) and resveratrol (5-100 M) treatment without any cytotoxic effect, while capsaicin exerted a cytotoxic effect only at the highest tested concentration (200 M). Mouse fibrosarcoma cells were more sensitive to the cytotoxic effect of all three compounds where Aeruginosin-865 (100-200 M) and resveratrol (50-100 M) showed high-dose cytotoxicity and capsaicin showed low-and high-dose cytotoxicity (25 M and 200 M). The three tested compounds at the highest concentrations were found to be cytotoxic to both liver-and kidney-derived cells from fallow deer. Overall, the results indicate that the cytotoxic effects of the three tested natural substances on cells derived from fallow deer and mouse tumour fibroblasts differ significantly from those exerted on normal fibroblasts. The results demonstrate the potential of these natural compounds as therapeutic agents and pave the way for future in vivo toxicological investigations.
Diethylnitrosamine (DEN) is proven to be toxic to kidneys and liver and to act as a potent carcinogen mainly in liver. Capsaicin (CAP) is an alkaloid produced by Capsicum genus plants and is considered to be a protective agent against toxicity and carcinogenicity of many substances including DEN. The aim of this study was to assess the toxicity of DEN and CAP in liver and kidneys in mice. The experiment started after two weeks of acclimatisation and was conducted according to the Czech animal welfare protection legal guidelines. At the end of the experiment the mice were sacrificed and the toxicity of DEN and CAP in liver and kidneys were analysed. The histopathological examination of the liver revealed multifocal lymphoplasmacytic reaction in parenchyma in DEN treated group. CAP used as both preventive and therapeutic agent caused reduction in number and extent of lesions. In CAP group mitotic figures were found indicating xenobiotic-induced hepatotoxicity or regenerative changes. In the kidneys DEN revealed also multifocal lymphoplasmacytic reaction that has been mitigated by CAP. Moreover histopathological observation of the kidney in DEN group has revealed granular dystrophy of the renal tubules which has not been presented in CAP treated mice. Levels of ALT, AST activity, total protein and albumin concentration was not statistically different among control and experimental groups. In this study mild protective effect of CAP on DEN-induced hepatotoxicity and nephrotoxicity was shown only in histopathological changes. The toxicity of CAP itself is questionable and further studies should be performed to verify its chemopreventive potential.
Diethylnitrosamine is well known for its toxic and carcinogenic properties affecting mainly liver and kidneys. Capsaicin has been proven in previous years as a promising protective agent against many health problems affecting modern people. In this study we used diethylnitrosamine induced mouse experimental model of liver and kidney damage to assess the potential chemopreventive effect of capsaicin in vivo. Fifty female ICR mice were randomly divided into five groups intraperitoneally administered 1% ethanol solution in controls, capsaicin to assess its toxicity, diethylnitrosamine alone, and diethylnitrosamine and capsaicin in combination in different manners in two groups. After 14 weeks all mice were sacrificed, complete necropsy was performed and liver and kidneys were used for further examination. Slides of both organs stained with haematoxylin and eosin were histologically evaluated and immunohistochemical detection of proliferating cell nuclear antigen and glutamine synthetase in the liver tissue was performed. Histological evaluation of the liver and kidneys revealed toxic damage of diethylnitrosamine treated animals, whereas mice that received the combination of the substances showed milder lesions. Proliferating cell nuclear antigen expression was lower in diethylnitrosamine treated animals compared to the control and capsaicin groups, pointing to a disruption of the proliferative activity of hepatocytes in the juvenile liver. Glutamine synthetase expression did not differ between the groups, indicating that no tumours were induced by any of the substances used in our study. In conclusion, our experiment demonstrated the toxic properties of diethylnitrosamine in mice liver and kidneys, with the promising beneficial effect of capsaicin.
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