SUBJECTS: Female Dark Agouti (DA) rats.
METHODS: Three different dosages of (2 mg/kg of body weight, 3 mg/kg of body weight and 4 mg/kg of body weight) collagen and complete Freund's adjuvant suspension were tested. After 45 days, serum C-reactive protein, TNF-α, superoxide dismutase and total glutathione assays were done. Radiographic and histopathological changes in the joints were compared.
RESULTS: All three groups showed signs of arthritic changes, confirmed by histopathological and radiographic changes. Severe arthritic changes were seen in the rats injected with 4 mg/kg of body weight of collagen. There was a significant increase in C-reactive protein, TNF-α, super oxide dismutase and total glutathione levels in the plasma in arthritis rats and the changes were more significant with 4 mg/kg of collagen.
CONCLUSION: These results demonstrated that the optimal dose to inject to experimental animals in order to get server arthritic changes was 4 mg/kg of collagen with complete Freund's adjuvant suspension. Severe arthritis changes induced significant elevation in plasma C-reactive protein and TNF-α levels.
MATERIALS AND METHODS: Anti-cancer activity of a tocotrienol-rich fraction (TRF) and a tocotrienol-enriched fraction (TEF) isolated from palm oil, as well as pure vitamin E analogues (α-tocopherol, α-, δ- and γ-tocotrienols) were studied using highly aggressive triple negative MDA-MB-231 cells and oestrogen-dependent MCF-7 cells, both of human breast cancer cell lines. Cell population growth was evaluated using a Coulter particle counter. Cell death mechanism, poly(ADP-ribose) polymerase cleavage and levels of NF-κB were determined using commercial ELISA kits.
RESULTS: Tocotrienols exerted potent anti-proliferative effects on both types of cell by inducing apoptosis, the underlying mechanism of cell death being ascertained using respective IC50 concentrations of all test compounds. There was marked induction of apoptosis in both cell lines by tocotrienols compared to treatment with Paclitaxel, which was used as positive control. This activity was found to be associated with cleavage of poly(ADP-ribose) polymerase (a DNA repair protein), demonstrating involvement of the apoptotic cell death signalling pathway. Tocotrienols also inhibited expression of nuclear factor kappa-B (NF-κB), which in turn can increase sensitivity of cancer cells to apoptosis.
CONCLUSION: Tocotrienols induced anti-proliferative and apoptotic effects in association with DNA fragmentation, poly(ADP-ribose) polymerase cleavage and NF-κB inhibition in the two human breast cancer cell lines.