ABSTRACT
We investigated the synergistic effect of combined treatment with red ginseng acidic polysaccharide (RGAP) from Panax ginseng C.A. Meyer and pidotimod in cyclophosphamide-treated mice. The combination of pidotimod and RGAP restored concanavalin A-induced splenic T cell proliferation and LPS-stimulated B cell proliferation significantly. The production of nitric oxide from peritoneal macrophages was increased by the combinations. NK cell activity was increased by RGAP alone or in combination with pidotimod. A synergistic increase in the level of serum IL-12 and interferongamm was observed when the combination of the two was used. RGAP alone or in combination with pidotimod modulated the level of serum C-reactive protein to a near-normal level. These results indicate that combinations of pidotimod and RGAP are synergistic and suggest that combination therapy using pidotimod and RGAP for improving immune activity may provide an additional benefit over the use of the two drugs by themselves.
Subject(s)
Adjuvants, Immunologic/pharmacology , Cyclophosphamide/antagonists & inhibitors , Cyclophosphamide/pharmacology , Immunosuppressive Agents/antagonists & inhibitors , Immunosuppressive Agents/pharmacology , Panax/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Pyrrolidonecarboxylic Acid/analogs & derivatives , Thiazolidines/pharmacology , Animals , Body Weight/drug effects , C-Reactive Protein/drug effects , C-Reactive Protein/metabolism , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Synergism , Killer Cells, Natural/drug effects , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/metabolism , Male , Mice , Mice, Inbred BALB C , Nitric Oxide/biosynthesis , Organ Size/drug effects , Pyrrolidonecarboxylic Acid/pharmacology , Spleen/cytology , Spleen/drug effects , Tetrazolium Salts , ThiazolesABSTRACT
We investigated the synergistic effect of pidotimod and red ginseng acidic polysaccharide (RGAP) from Panax ginseng C.A. Meyer on humoral immune response challenged by lipopolysaccharide (LPS) and sheep red blood cells (SRBC) in immunosuppressed mice. Combined treatment with pidotimod and RGAP significantly increased the number of plaque-forming cells in the spleen in response to both LPS and SRBC, while treatment with either pidotimod or RGAP individually had no such effect. IgG levels in serum were augmented for secondary responses to SRBC in co-treated mice, but not in mice treated with either drug alone. Microscopic studies revealed that architecture of the spleen, thymus, and lymph nodes was conserved. GPT and creatinine in serum as indicators of hepatic and renal functions showed no difference compared to the control group. These results indicate that combined treatment with pidotimod and RGAP has an immunostimulatory effect in a synergistic manner on antibody response to challenge with LPS and SRBC without toxic changes.
Subject(s)
Adjuvants, Immunologic/pharmacology , Antibody Formation/drug effects , Immunosuppression Therapy , Panax/chemistry , Polysaccharides/pharmacology , Pyrrolidonecarboxylic Acid/analogs & derivatives , Thiazolidines/pharmacology , Alanine Transaminase/blood , Animals , Antineoplastic Agents, Alkylating/pharmacology , Cell Count , Cyclophosphamide/pharmacology , Drug Synergism , Erythrocytes/drug effects , Erythrocytes/immunology , Female , Immunoglobulin E/biosynthesis , Immunoglobulin E/genetics , Immunoglobulin G/biosynthesis , Immunoglobulin G/genetics , Kidney Function Tests , Leukocytes/drug effects , Liver Function Tests , Lymph Nodes/immunology , Lymph Nodes/pathology , Mice , Mice, Inbred BALB C , Panax/toxicity , Plant Extracts/pharmacology , Polysaccharides/chemistry , Polysaccharides/toxicity , Pyrrolidonecarboxylic Acid/pharmacology , Pyrrolidonecarboxylic Acid/toxicity , Spleen/immunology , Spleen/pathology , Thiazolidines/toxicity , Thymus Gland/immunology , Thymus Gland/pathologyABSTRACT
2-Bromopropane (2-BP), a halogenated propane analogue, is a substitute for chlorofluorocarbones. The present study was carried out to investigate the potential adverse effects of 2-BP on pregnant dams and embryo-fetal development after maternal exposure on gestational days (GD) 6 through 19 in Sprague-Dawley rats. The test chemical was administered subcutaneously to pregnant rats at dose levels of 0, 250, 500, and 1000 mg/kg per day. All dams were subjected to caesarean section on GD 20 and their fetuses were examined for external, visceral and skeletal abnormalities. In the 1000 mg/kg group, maternal toxicity included an increase in the incidence of abnormal clinical signs, a suppression in the body weight and body weight gain, and a decrease in the food intake. Developmental toxicity included an increase in the fetal deaths, a decrease in the litter size, and a reduction in the fetal body weight. In addition, an increase in the incidence of fetal external, visceral, and skeletal abnormalities was seen. In the 500 mg/kg group, minimal developmental toxicity including decreased fetal body weight and increased fetal ossification delay was observed. There were no adverse effects on either pregnant dams or embryo-fetal development in the 250 mg/kg group. These findings suggest that a 14-day subcutaneous dose of 2-BP is embryotoxic and teratogenic at a maternally toxic dose (i.e., 1000 mg/kg per day) and is minimally embryotoxic at a nonmaternally toxic dose (i.e., 500 mg/kg per day) in Sprague-Dawley rats. In the present experimental conditions, the no-observed-adverse-effect level (NOAEL) of 2-BP is considered to be 500 mg/kg per day for dams and 250 mg/kg per day for embryo-fetal development.
