C60 fullerene and its nanocomplexes with anticancer drugs modulate circulating phagocyte functions and dramatically increase ROS generation in transformed monocytes.

BACKGROUND: C60 fullerene-based nanoformulations are proposed to have a direct toxic effect on tumor cells. Previous investigations demonstrated that C60 fullerene used alone or being conjugated with chemotherapeutic agents possesses a potent anticancer activity. The main aim of this study was to investigate the effect of C60 fullerene and its nanocomplexes with anticancer drugs on human phagocyte metabolic profile in vitro. METHODS: Analysis of the metabolic profile of phagocytes exposed to C60 fullerene in vitro revealed augmented phagocytic activity and down-regulated reactive nitrogen species generation in these cells. Additionally, cytofluorimetric analysis showed that C60 fullerene can exert direct cytotoxic effect on normal and transformed phagocytes through the vigorous induction of intracellular reactive oxygen species generation. RESULTS: Cytotoxic action as well as the pro-oxidant effect of C60 fullerene was more pronounced toward malignant phagocytes. At the same time, C60 fullerenes have the ability to down-regulate the pro-oxidant effect of cisplatin on normal cells. These results indicate that C60 fullerenes may influence phagocyte metabolism and have both pro-oxidant and antioxidant properties. CONCLUSIONS: The antineoplastic effect of C60 fullerene has been observed by direct toxic effect on tumor cells, as well as through the modulation of the functions of effector cells of antitumor immunity.

Sex-based differences in phagocyte metabolic profile in rats with monosodium glutamate-induced obesity.

The important component of obesity pathogenesis is inflammatory activation of innate immune cells within adipose tissue and in other body locations. Both the course of obesity and innate immune reactivity are characterized by sex-associated differences. The aim of the work was a comparative investigation of metabolic profiles of phagocytes from different locations in male and female rats with MSG-induced obesity. The administration of monosodium glutamate (MSG) caused obesity, with sex-associated differences, that was more severe in male rats. Obesity was associated with pro-inflammatory activation of CD14+ phagocytes from adipose tissue in female, but not in male rats, which was demonstrated by decreased phagocytosis activity along with increased ROS generation. Phagocytes from the peritoneal cavity and peripheral blood of obese female rats exhibited neutral metabolic profile, whereas those cells from obese male rats displayed a pro-inflammatory metabolic profile. Thus, the manifestation of obesity-induced inflammation was characterized by different patterns of metabolic profile of phagocytes in male and female rats. Identified immune cell characteristics expand our knowledge of obesity immunobiology and may help to develop more effective preventive and therapeutic interventions for obese patients of different sexes.