Liver antioxidant and aerobic status improves after metformin and melatonin administration in a rat model of high-fat diet and mammary carcinogenesis

Oxidative stress is involved in the development of various cancers. In the present study the effect of long-term administration of peroral antidiabetic metformin and pineal hormone melatonin on liver antioxidant and aerobic status in female Sprague-Dawley rats carrying mammary tumors induced by N-methyl-N-nitrosourea was evaluated. Both substances were administered in a preventive/curative manner (12 days before and 16 weeks after the carcinogen application). Carcinogen administration induced oxidative stress: the level of thiobarbituric acid reactive products (TBARS) as a marker of reactive oxygen species (ROS) generation in liver increased as well as the level of oxidatively modified protein content (OMP, aldehyde and ketone derivates). Metformin administration restored succinate dehydrogenase and lactate dehydrogenase activity and associated ROS production and OMP content to the level of intact rats, with predominant activation of superoxide dismutase (SOD) and glutathione reductase (GR). Melatonin alone and in combination with metformin decreased TBARS content too. OMP content decreased in all groups receiving chemoprevention. The rise in total antioxidant capacity after melatonin and particularly metformin and melatonin combination might result from the initiation of anaerobic metabolism and increasing SOD, GR and glutathione peroxidase (GPx) activity. Long-term administration of metformin and melatonin exerts antioxidant properties in liver, especially in combination.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Dietary Fat and Cancer—Which Is Good, Which Is Bad, and the Body of Evidence

A high-fat diet (HFD) induces changes in gut microbiota leading to activation of pro-inflammatory pathways, and obesity, as a consequence of overnutrition, exacerbates inflammation, a known risk factor not only for cancer. However, experimental data showed that the composition of dietary fat has a greater impact on the pathogenesis of cancer than the total fat content in isocaloric diets. Similarly, human studies did not prove that a decrease in total fat intake is an effective strategy to combat cancer. Saturated fat has long been considered as harmful, but the current consensus is that moderate intake of saturated fatty acids (SFAs), including palmitic acid (PA), does not pose a health risk within a balanced diet. In regard to monounsaturated fat, plant sources are recommended. The consumption of plant monounsaturated fatty acids (MUFAs), particularly from olive oil, has been associated with lower cancer risk. Similarly, the replacement of animal MUFAs with plant MUFAs decreased cancer mortality. The impact of polyunsaturated fatty acids (PUFAs) on cancer risk depends on the ratio between ω-6 and ω-3 PUFAs. In vivo data showed stimulatory effects of ω-6 PUFAs on tumour growth while ω-3 PUFAs were protective, but the results of human studies were not as promising as indicated in preclinical reports. As for trans FAs (TFAs), experimental data mostly showed opposite effects of industrially produced and natural TFAs, with the latter being protective against cancer progression, but human data are mixed, and no clear conclusion can be made. Further studies are warranted to establish the role of FAs in the control of cell growth in order to find an effective strategy for cancer prevention/treatment

Detrimental effects of fluvastatin on plasma lipid metabolism in rat breast carcinoma model

From clinical practice, obvious positive effects of statins on plasma lipid metabolism are well known. On the other hand, there are several experimental rodent studies, where these beneficial effects were not confirmed. The effects of fluvastatin on selected serum lipid parameters in a rat model of experimental breast cancer were determined. The drug was dietary administered at two concentrations of 20 and 200 mg/kg. At the end of the study (experiment duration - 18 weeks) the blood from each animal was collected and serum lipid parameters were evaluated. Fluvastatin in both treated groups significantly increased parameters of serum lipids (mostly in a dose dependent manner). Fluvastatin in both treated groups of animals significantly increased serum levels of triacylglycerols, total cholesterol, and LDL-, HDL-, VLDL-cholesterol when compared to the control group. Our results pointed out to the apparent harmful effects of fluvastatin on plasma lipid metabolism in rat mammary carcinogenesis. Based on our previous results, it seems that rats commonly used in cancer model studies are generally unresponsive to the hypocholesterolemic effects of statins