关键词: 猪链球菌2型, 肝脏药物代谢酶, 肝微粒体蛋白, 药物毒性

Abstract:

【Objective】 The effect of Streptococcus suis infection on both phase I (oxidative) and phase II (conjugative) microsomal enzyme activities was investigated in a well-characterized mice infection model. 【Method】 One hundred and twenty ICR mouse were used and divided randomly into infection groups (HA9801 group and SS2-H group) and negative control group. Each infected mouse was inoculated intraperioneally with one ml inoculum containing 1/2LD50 of each strain. One control group of mice was injected with one ml of sterile water. Body weight were weighed every day and the levels of liver microsomal protein, activities of cytP450, cytb5, NCCD, ERND, AND, AH and GSH-S-T were determined on 3, 5, 10, 15 days, respectively. 【Result】 Intraperitoneal injection of Streptococcus suis resulted in a time-dependent modulation of hepatic drug- metabolizing enzymes activities in mice. The activities of some drug-metabolizing enzymes of infected groups were significantly lowered compared with the negative control group during different infectious days, especially on 10 day post-infection, the lowest levels of cytP450, cytb5, NCCD, AH and ERND were achieved. While between the two infected groups, there was no obvious difference in the levels of all the enzymes tested except the levels of cytP450 and cyt b5 at the early stage. 【Conclusion】 The present study is the first to show that the infection by S. suis can decrease the activities of some hepatic drug-metabolizing enzymes in mice. If such a response also occurs in humans, this has the potential to produce serious complications with drug and endogenous substrate metabolism in patients with an infectious disease. The results also suggest that drugs with narrow therapeutic indices are dangerous during therapeutic schedule and should be administered with caution during infectious diseases caused by S. suis or other bacteria and viruses.

Key words: S.suis, drug-metabolizing enzymes, liver microsomal protein, drug toxicity