Abstract
Bioactive compounds such as benzoquinone derivates presented in fermented wheat germ extract (FWGE) have several positive effects on overall health status of humans and animals alike. Since available data regarding the antioxidant activity of FWGE are limited, the aim of our study was to investigate its effects on the cellular redox homeostasis applying primary hepatocyte cell cultures of rat origin. Cultures were challenged to lipopolysaccharide (LPS) treatment for 2 or 8 hours to trigger inflammatory response. Further, culture media were concomitantly supplemented with or without FWGE (Immunovet®, 0.1% and 1%). In order to monitor the metabolic activity of the cell cultures, CCK-8 test was applied, while reactive oxygen species (ROS) production was measured using Amplex Red method. Malondialdehyde concentration of culture media as a specific marker of lipid peroxidation and the activity of glutathione peroxidase in cell lysates were also determined to monitor the redox status of the cultures. Based on our findings, it can be concluded that FWGE did not show cytotoxic effects in any applied concentration in cell cultures. Furthermore, FWGE efficiently decreased cellular ROS production and lipid peroxidation rate in case of LPS-induced inflammatory response. However, without LPS treatment, higher concentration of FWGE increased the rate of both ROS and malondialdehyde synthesis. This observation may refer to the prooxidant activity of high dose FWGE, which is an important beneficial effect regarding tumor cells. However, in case of noninflamed hepatocytes, considering the results of glutathione peroxidase activity, the application of the product did not result in severe oxidative distress. In accordance with the abovementioned findings, FWGE as a redox modulator, applied in the appropriate concentration, can serve as a promising candidate in the supplementary therapy of patients suffering from various inflammatory diseases, decreasing the free radical generation, thus avoiding the occurrence of cytotoxic effects.
Highlights
Based on its various beneficial biological effects, fermented wheat germ extract (FWGE) is successfully used in human medicine, mainly in the supportive therapy of people suffering from cancer
The FWGE stimulates the immune response against tumor cells by decreasing the MHC-I expression in the cell membrane and rendering cancer cells more effectively be recognized by natural killer (NK)
FWGE impedes the activity of ribonucleotide reductase enzyme, directly decelerating the production of nucleotides needed for the DNA synthesis [6]
Summary
Based on its various beneficial biological effects, fermented wheat germ extract (FWGE) is successfully used in human medicine, mainly in the supportive therapy of people suffering from cancer. FWGE increases tumor necrosis factor α (TNFα) production by macrophages, leading to improved immune response towards tumor cells, inhibition of angiogenesis, and increased apoptosis of the target cells [2]. By the inhibition of hexokinase enzyme, it is able to decrease cellular ATP production and hinder the synthesis of pentoses, which are necessary for cell division [5]. As a result of all the mentioned effects, FWGE is able to effectively decrease the proliferation of several malignant tumor types and to increase the apoptosis of these cells. These findings were initially confirmed in studies on HT-29 colorectal adenocarcinoma and HL-60 leukaemia cell lines [2]. The decreased velocity of tumor growth and metastasis formation was described in case of numerous forms of tumors, such as in melanoma, in neuroblastoma, and in different cervical, testicular, or thyroid cancer types [6]
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