Curcumin enhances non-inflammatory phagocytic activity of RAW264.7 cells.

Present study was performed to assess the effect of curcumin treatment on macrophage functions using RAW264.7 cells, a murine macrophage cell line. Phagocytic activity of RAW264.7 cells was enhanced by the treatment with curcumin for 48 hours while the nitric oxide synthesis from RAW264.7 cells following lipopolysaccharide exposure was blocked. The incubation of RAW264.7 cells with curcumin dose-dependently inhibited the stimulatory responses of macrophage triggered by lipopolysaccharide; the enhanced secretion of inflammatory cytokines such as TNF-alpha and IL-1beta and the up-regulated expression of surface antigens like CD14 and CD40. Curcumin alone, however, was able to increase the basal level of TNF-alpha secretion and elevated markedly the expression of CD14 and slightly CD40. The marked enhancement of both phagocytic activity and CD14 was detectable as early as 75min after curcumin treatment which is the minimum time period required for the phagocytosis and CD14 measurement, suggesting a signaling pathway distinct from that triggered by apoptotic cells. In conclusion, this study elucidates that curcumin treatment enhances the phagocytic activity with blocking nitric oxide synthesis, a scavenger function of macrophages in non-inflammatory condition. In addition, this enhancement of phagocytic activity is triggered directly by the signals from curcumin itself not by apoptotic cells.

Role of metabolism by flavin-containing monooxygenase in thioacetamide-induced immunosuppression.

Thioacetamide has been known to cause immune suppression. The object of the present study is to investigate the role of metabolic activation by flavin-containing monooxygenases (FMO) in thioacetamide-induced immune response. To determine whether the metabolites of thioacetamide produced by FMO causes the immunosuppression, methimazole, an FMO inhibitor, was used to block the FMO pathway. Antibody-forming cell (AFC) response measured in BALB/c mice sensitized with sheep red blood cells (SRBCs) was compared between the groups treated with thioacetamide in the presence or absence of methimazole pretreatment. The pretreatment abolished the decrease in AFC number observed in the mice treated with thioacetamide alone. In addition, when spleen cells isolated from untreated mice were exposed to thioacetamide with a drug-metabolizing system, liver microsome and NADPH, for 4 h in vitro prior to the stimulation with mitogens, such as lipopolysaccharide (LPS) or concanavalin A (Con A), spleen cell proliferation was also decreased. The inhibitory effect of thioacetamide on cell growth was not detectable without the liver microsome. Moreover, the thioacetamide-suppressed proliferation of spleen cells in the presence of the metabolic activation system was prevented when coincubated with either SKF-525A, a cytochrome P450 (P450) inhibitor, or methimazole. We also found that the level of interleukin-2 (IL-2) in the culture supernatant was decreased by thioacetamide treatment and that the decrease of IL-2 level can be prevented by either SKF-525A or methimazole coincubation. Since IL-2 is one of the responsible factors that determine the proliferation level of lymphocytes, the change of IL-2 production was consistent with that of lymphoproliferation. In conclusion, thioacetamide-induced immunosuppression was, at least in part, due to the metabolites produced by FMO as well as by P450.

Skeletal muscle atrophy induced by intramuscular repeated dose of botulinum toxin type A in rats.

Botulinum toxin type A was intramuscularly administered to Sprague-Dawley rats once a day for 28 days at doses of 1, 3, and 9 ng kg-1 day-1 to investigate the possibility of unanticipated toxicity of repeated dose. A dose-related decrease in body weight gain was noted and lasted throughout the 4-week recovery period. Paralytic gait was a common clinical sign observed in the animals dosed at >or=3 ng kg-1 day-1 and muscle atrophy at 9 ng kg-1 day-1. Decreased creatinine was monitored in both males and females treated at 9 ng kg-1 day-1. Microscopic examination of the quadriceps femoris muscle, the test article application site, confirmed the muscle atrophy with a decrease in myofiber diameter and an increase of myofiber nuclei and intermyofiber connective tissue. Although antibody against botulinum toxin type A was detected in the sera from both males and females at 9 ng kg-1 day-1, no immunogenicity-related changes or lesions were noted. In conclusion, no other side effects of the botulinum toxin type A injection except the decrease in body weight gain and the muscle atrophy at the administration site were noted in the 28-day intramuscular repeated dose study.