Influence of arecoline on immune system: I. Short term effects on general parameters and on the adrenal and lymphoid...

Arecoline, a suspected carcinogenic/cocarcinogenic alkaloid was screened to explore in detail its immunomodulatory influence in murine model system. The oral LD50 value for male mice was 371 mg/kg bw whereas it was 309 mg/kg bw for female mice. The subcutaneous LD50 value for both sexes was 97 mg/kg bw. Only a marginal difference was observed in intraperitoneal LD50 values between male (120 mg/kg bw) and female (109 mg/kg bw) mice. Arecoline was administered subcutaneously to male mice at subtoxic dose levels (5, 10, and 20 mg/kg bw) for 1, 2 and 3 weeks on a daily basis. In groups where significant decreases in body weight were present (at 20 mg/kg bw for both sexes), reductions in thymus weight were also noted. Spleen, mesenteric lymph nodes (MLN), liver, and kidney showed moderate reductions in their weights. Histopathological effects at 20 mg/kg bw included lymphocyte depletion of the thymic cortex, and the B and T lymphocyte areas in spleen and MLN. In concordance with the zona fasciculata hypertrophy of adrenals, corticosterone concentration in serum increased depending on the dose with a significant elevation at 20 mg/kg bw. While total protein, albumin, glucose, acid phosphatase and hemoglobin concentrations were not altered, increases in SGOT and SGPT levels were observed at the high dose. The white and red blood cell counts decreased in a dose-dependent manner. Marked reduction in cell number of thymus, and moderate effect on cellularity of spleen and MLN, were observed at 20 mg/kg bw. In vitro exposure of rat thymocytes to arecoline resulted in a biphasic oxygen consumption response with progressive increase in oxygen consumption, reaching a maximum value at 10(-5) M and decreasing sharply at 10(-3) M. Exogenously added substrates such as glucose, pyruvic acid and lactic acid retarded the fall in the oxygen consumption induced at 10(-3) M arecoline. These observations demonstrate the effects of arecoline on lymphoid organs, which may be due to its direct action or through the elevation of corticosterone.