The effect of C60 "micronized fullerene was tested by a manual and automatised (Analyzer Bioscreen C(R)) micromethod on the microbial growth of 22 collection strains: E. coli (5), P. aeruginosa (2), S. Typhimurium (6), S. aureus (2), L. monocytogenes (2), E. hirae (1), B. cereus (1), B. subtilis (1), B. pumilus (1) et C. albicans (1). No effect on microbial growth was observed with C60 "micronized fullerene (43.2 microg/ml) on all strains studied: no difference was found with doubling time, slope and growth rate constant. The results of cytotoxicity obtained with animal models or in vitro cultures as human monocyte, leukocyte or macrophage confirm the absence of effect of C60 fullerene at a concentration compatible with microbial or biological models. This study is included in research program headed "Therapeutics perspectives of fullerenes.
The sensitivity of rat brain astrocytes and human fibroblasts in culture to unconjugated bilirubin was investigated. Medium containing 6 μmol/1 bilirubin and increasing concentrations of human serum albumin giving ratios of 0.5–1.5 that resulted in an increase of the free bilirubin concentrations. The LDH activity in the culture medium was an index of cytolysis and the MTT assay was used as an index of mitochondrial impairment. The ratios producing half-maximum cell lysis after 24, 48, and 72h, were 1.1, 0.9 and 0.85, for astrocytes, and 1.2, 0.75 and 0.75, for fibroblasts. Mitochondrial activity decreased after 24 h for ratio = 0.7 and partly recovered at 48 h. Mitochondrial activity was more impaired in fibroblasts than in astrocytes above ratio = 0.7. The cytotoxic effects were linked to the free bilirubin concentration. We conclude that astrocytes are less sensitive to bilirubin cytotoxic effects than are fibroblasts.
Abstract High amounts of micronized C60 have been injected intraperitoneally into Swiss mice. Until the fourteenth day, they were still alive without any behaviour trouble. C60 was well absorbed, and found localized in spleen and liver. Inside the liver, C60 was
Thyroid hormone (TH) metabolism is altered in cases of unconjugated hyperbilirubinemia. These effects might involve inhibition of TH uptake by their target cells. Astrocytes, which are in close contact with the membranes of brain capillaries, might be the first brain cells to come into contact with bilirubin. Cultured rat brain astrocytes were used as a model to study the effects of bilirubin and bilirubin analogues on TH uptake. The initial uptake of [125I]T3 and [125I]T4 was inhibited by unconjugated bilirubin, biliverdin, ditaurobilirubin and bilirubin glucuronides. The inhibition of T3 uptake by the bilirubin analogues was competitive. The Ki values were: unconjugated bilirubin (31 μM), biliverdin (48 μM), ditaurobilirubin (2.5 μM) and bilirubin glucuronides (1.2 μM). This last value is similar to the Km of T3 transport (0.4 μM), indicating that bilirubin glucuronides have a high affinity for the TH transport system. By contrast, the uptakes of [3H]tryptophan and [3H]glutamine were not inhibited. These results suggest that the astrocyte plasma membrane bears specific bilirubin-interaction sites that are closely related to the TH transport system. However, uptake of [14C]bilirubin by cultured astrocytes was a non-saturable process. Binding of bilirubin to the astrocyte plasma membrane may inhibit the TH uptake and impair their metabolism and their action on the intracellular targets.