Alterations in rat gut bacteria and intestinal epithelial cells following experimental exposure of antimicrobials

Abstract

The intestinal bacteria are known to play a significant role in intestinal homoeostasis and the mucosal immune system. In vitro interactions of Ampicillin (0.5-2.0 mg mL À1 ), Amphotericin-B (25-200 mg mL À1 ) and Ciprofloxacin (50-500 ng mL À1 ) with Escherichia coli, Pseudomonas sp. (Gram-negative), Lactobacillus sp., Staphylococcus sp. (Gram-positive), total mixed population of gut bacteria and intestinal epithelial cells were studied. In vitro exposure of Ciprofloxacin showed significant dose-dependent inhibition throughout the growth phase in bacteria. Similar patterns of concentration-dependent changes in membrane transport enzymes and structural constituents, dehydrogenase activity associated with respiratory and energy-producing processes and esterase activity test linked to the general heterotrophic activity of the cell were observed in both bacteria and epithelial cells. The antibiotic effects were in the order of Amphotericin-B o Ampicillin o Ciprofloxacin. Validation studies were conducted using rat intestinal loops filled with different concentrations of antibiotics and incubated for 30 min. In situ changes in epithelial cell membrane enzymes and constituents also indicated similar trends as observed following in vitro exposures. The findings suggest that these antibiotics exert similar cytotoxic effects on intestinal epithelial cells and gut bacteria. Thus, gut bacteria can be used for in vitro screening of gastrointestinal-cellular toxicity caused by antibiotics.

Experimental impact of aspirin exposure on rat intestinal bacteria, epithelial cells and cell line

“…The suitability is due to their easy handling, quicker response and the presence of most of biochemical pathways similar to those present in the cells of higher animals. [9][10][11][36][37][38] Similarities in most of the tested responses and effects of aspirin between IEC, IEC-6 cell line and bacteria as observed in the present study further strengthen the notion that gut bacteria and the IEC-6 cell line can be used as an alternate to animals for screening of GI cellular toxicity caused by new NSAIDs.…”

The effect of aqueous extract of caraway seed (<i>Carum carvi</i>) on cholecystokinin hormone in male rat

“…The presence of antimicrobial compounds stops combining of pathogenic microorganisms, leads to the growth and reproduction of beneficial intestinal bacteria, and thereby enhances the process of digestion of fat metabolism (18,19). On the other hand, intestinal micro-flora (Gut Microflora) could lead to the expression of genes involved in lipid metabolism (20)(21)(22).…”

Antibiotic Driven Changes in Gut Motility Suggest Direct Modulation of Enteric Nervous System

“…If treatment continues for an extended period of time, the reduction in intracellular Na + and diminished pump activity is maintained by altered transcriptional activities. When amphotericin B was tested in a cocktail with ampicillin and ciprofloxacin on a rat intestinal epithelial preparation in vitro , comparable concentration-dependent inhibition of alkaline phosphatase and an increase in Ca 2+ Mg 2+ ATPase was observed (Upreti et al, 2008 ). These authors predicted that these changes could hinder ion transport and possibly induce cytotoxic responses (Jornot et al, 2005 ; Upreti et al, 2008 ).…”

“…We speculate that, although we did not test antifungal agents, if our antibiotics compromised neuronal membrane integrity in a similar manner, the consequence may have been an influx of calcium ions from the calcium rich extracellular solution. At the lowest doses, the absence of changes to membrane excitability (and gut motility) may be due to normal metabolic processing by cellular organelles, like the mitochondria and endoplasmic reticulum, effectively removing excess calcium ions (Upreti et al, 2008 ). At slightly higher doses of antibiotics, the increased intracellular calcium may affect neuronal function, to produce the most distinct changes to parameters of gut motility.…”