Nonsteroidal anti-inflammatory drug diclofenac accelerates the emergence of antibiotic resistance via mutagenesis.

Overuse of antimicrobial agents are generally considered to be a key factor in the occurrence of antibiotic resistance bacteria (ARB). Nevertheless, it is unclear whether ARB can be induced by non-antibiotic chemicals such as nonsteroidal anti-inflammatory drug (NSAID). Thus, the objective of this study is to investigate whether NSAID diclofenac (DCF) promote the emergence of antibiotic resistance in Escherichia coli K12 MG1655. Our results suggested that DCF induced the occurrence of ARB which showed hereditary stability of resistance. Meanwhile, gene variation was identified on chromosome of the ARB, and DCF can cause bacterial oxidative stress and SOS response. Subsequently, transcriptional levels of antioxidant (soxS, sodA, sodC, gor, katG, ahpF) and SOS (recA, lexA, uvrA, uvrB, ruvA, ruvB, dinB, umuC, polB) system-related genes were enhanced. However, the expression of related genes cannot be increased in high-dosage treatment compared with low-dosage samples because of cytotoxicity and cellular damage. Simultaneously, high-dosage DCF decreased the mutation frequency but enhanced the resistance of mutants. Our findings expand our knowledge of the promoting effect on the emergence of ARB caused by DCF. More attention and regulations should be given to these potential ecological and health risks for widespread DCF.

[Influence of match-pair of huanglian-rougui on rat intestinal absorption of total huanglian alkali].

OBJECTIVE: To research the principle of match-pair of huanglian-rougui. METHOD: A rat intestinal model in vitro had been applied to investigate the absorption and transport characteristics of total huanglian alkali across intestinal mucosa, as well as the influence of match-pair of huanglian-rougui on its intestinal absorption. The identification of alkalis in primitive solution, serosal solution and intestinal homogenate were analyzed by TLC. RESULT: The transport and uptake characteristic of total alkali in huanglian solution was similar to berberine. The uptake and transport of total alkali across intestinal mucosa was concentration-and time-dependent. Transport directions had strong effects on the transport of total alkali. The amount of total alkali transport from serosal side to mucosal side was much more than that from mucosal side to serosal side. After matching with rougui as some ration, the intestinal absorption of total alkali increased significantly comparing with huanglian alone, and there was an optimal ration among match-pair of huanglian-rougui. CONCLUSION: Chemical reaction in vitro and intestinal absorption were the key factors of match-pair of huanglian-rougui.