Wheeler L A, Soderberg F B, Goldman P
J Pharmacol Exp Ther. 1975 Jul;194(1):135-44.
The capacity of rats to reduce a 25-mg dose of p-nitrobenzoic acid (PNBA) was measured by quantifying the amount of this compound recovered in the urine as p-aminobenzoic acid (PABA) and its conjugates. It was found that germfree rats converted approximately 1% of PNBA to PABA; in conventional rats the conversion was approximately 25%. Various bacteria isolated from the rat cecum were selectively associated with germfree rats and it was demonstrated that these bacteria colonized their gastrointestinal tracts. In assoication with Lactobacillus plantarum, the conversion of PNBA to PABA increased to 3.9%. When these rats were further associated with Clostridium sp. and Streptoccocus faecalis, the conversion increased to approximately 12%. A general correlation was found between the capacity of constituents of the microflora to reduce PNBA in vitro and when associated with the germfree rat. Cecectomy, which removes a substantial portion of the microflora of the rat, decreases the capacity of the conventional rat to reduce PNBA. Similar experiments with p-nitrobenzenesulfonamide indicate that this compound is also largely reduced by the flora. Evidence that the reduction of the nitro group in these compounds is carried out by the intestinal microflora explains previous observations in which the reduction of these compounds in rats did not correlate with the activity of liver enzymes putative for these reactions.
通过对大鼠尿液中回收的对氨基苯甲酸(PABA)及其共轭物的量进行定量,来测定大鼠对25毫克对硝基苯甲酸(PNBA)的代谢能力。结果发现,无菌大鼠仅将约1%的PNBA转化为PABA;而在普通大鼠中,这一转化率约为25%。从大鼠盲肠分离出的各种细菌被选择性地与无菌大鼠关联,结果表明这些细菌在其胃肠道中定殖。与植物乳杆菌关联后,PNBA向PABA的转化率提高到了3.9%。当这些大鼠再与梭菌属和粪肠球菌关联时,转化率提高到了约12%。研究发现,微生物群落成分在体外以及与无菌大鼠关联时还原PNBA的能力之间存在普遍相关性。切除大鼠大部分微生物群落的盲肠切除术,会降低普通大鼠还原PNBA的能力。对对硝基苯磺酰胺进行的类似实验表明,该化合物也主要由微生物群落还原。这些化合物中硝基的还原是由肠道微生物群落完成的这一证据,解释了之前的一些观察结果,即在大鼠中这些化合物的还原与假定参与这些反应的肝脏酶的活性不相关。