Selvan R S, Venkateswaran K S, Rao A R
Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Immunopharmacol Immunotoxicol. 1989;11(2-3):347-77. doi: 10.3109/08923978909005375.
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.
槟榔碱是一种疑似致癌/促癌生物碱，对其在小鼠模型系统中的免疫调节作用进行了详细筛选。雄性小鼠的口服半数致死量（LD50）值为371毫克/千克体重，而雌性小鼠为309毫克/千克体重。两性的皮下LD50值均为97毫克/千克体重。雄性（120毫克/千克体重）和雌性（109毫克/千克体重）小鼠的腹腔内LD50值仅观察到微小差异。每天以亚毒性剂量水平（5、10和20毫克/千克体重）对雄性小鼠进行皮下注射槟榔碱，持续1、2和3周。在体重显著下降的组中（两性均为20毫克/千克体重），还注意到胸腺重量减轻。脾脏、肠系膜淋巴结（MLN）、肝脏和肾脏的重量有中度减轻。20毫克/千克体重时的组织病理学效应包括胸腺皮质淋巴细胞耗竭，以及脾脏和MLN中的B和T淋巴细胞区域。与肾上腺束状带肥大一致，血清皮质酮浓度随剂量增加而升高，在20毫克/千克体重时显著升高。虽然总蛋白、白蛋白、葡萄糖、酸性磷酸酶和血红蛋白浓度未改变，但在高剂量时观察到谷草转氨酶（SGOT）和谷丙转氨酶（SGPT）水平升高。白细胞和红细胞计数呈剂量依赖性下降。在20毫克/千克体重时，观察到胸腺细胞数量显著减少，对脾脏和MLN细胞数量有中度影响。大鼠胸腺细胞在体外暴露于槟榔碱会导致双相耗氧反应，耗氧量逐渐增加，在10^(-5) M时达到最大值，在10^(-3) M时急剧下降。外源性添加的底物如葡萄糖、丙酮酸和乳酸可延缓10^(-3) M槟榔碱诱导的耗氧量下降。这些观察结果证明了槟榔碱对淋巴器官的影响，这可能是由于其直接作用或通过皮质酮的升高所致。
