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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. Glutamine synthetase, liver, kidney, proliferating cell nuclear antigen Cancer is one of the leading causes of morbidity and mortality worldwide. In 2012, approximately 14 million new cases have emerged globally and in 2015 cancer accounted for 8.8 million of deaths (Stewart and Wild 2014; WHO 2018). In 2017, about 1 688 780 new cancer diagnoses and 600 920 cancer deaths were estimated in the United States and the predicted number of cancer deaths in the European Union for 2017 was 1 373 500 (Malvezzi et al. 2017; Siegel et al. 2017). Liver cancer is the second most common cause of cancer death after lung cancer and the most common primary malignancy of the liver is the hepatocellular carcinoma (HCC) (Stuver and Trichopoulos 2008; WHO 2018). The aetiology and pathogenesis of HCC is very heterogeneous but there is a significant role of both intrinsic genetic factors and extrinsic influences such as viral infections (hepatitis B and C), alcohol or other chronic liver disease that predispose one to the HCC development (Ghouri et al. 2017). Almost 90% of HCC in humans arises from cirrhosis and there is a clear association between HCC and chronic inflammation or fibrosis (Seitz and Stickel 2006; Zhang and Friedman 2012). Nitrosamines are substances well known for their toxic properties, the effect of dimethylnitrosamnie (DMN) on liver damage was reported as early as in 1937 (Freund 1937). Currently, one of the most commonly used experimental models for liver damage ACTA VET. BRNO 2020, 89: 383–389; https://doi.org/10.2754/avb202089040383 Address for correspondence: MVDr. Ivana Veselá, Ph.D. University of Veterinary and Pharmaceutical Sciences Brno Palackého tř. 1946/1, 612 42 Brno, Czech Republic Phone: +420 541 562 303 E-mail: [email protected] http://actavet.vfu.cz/