Oxidant-scavenging activities of ampicillin and sulbactam and their effects on neutrophil functions

Abstract

Luminol-enhanced luminescence is a method used to measure formation of reactive oxygen intermediates important in the ability of neutrophils to kill microbes. Several studies have demonstrated that under some conditions of incubation, ampicillin can inhibit neutrophil-derived luminol-enhanced luminescence. We evaluated the mechanism(s) by which ampicillin inhibited the luminescent response of stimulated neutrophils.We also investigated sulbactam, a 13-lactamase inhibitor which has been given in combination with ampicillin and other beta-lactam antibiotics to increase their spectra, for possible similar effects. Both ampicillin and sulbactam attenuated luminol-enhanced luminescence by approximately 40%. Superoxide production was not prevented by added ampicillin, nor was superoxide scavenged by it. Myeloperoxidase reacts with H202 and Clto generate OCl-, which is believed to be the oxidizer of luminol that is primarily responsible for enhancement of neutrophil-derived luminescence. Hydroxyl radicals (HO'), which may also oxidize luminol, resulting in luminescence, can be formed from 02 and H202 via either myeloperoxidase-dependent (involving intermediate OCI-) or myeloperoxidase-independent (through a metal ion catalyst) reactions. Ampicillin scavenged H202 and OCl-and prevented 95% of Fenton reaction-generated HO' from reacting with 5,5-dimethyl-1-pyrroline-N-oxide. Sulbactam was found to scavenge OCl-and HO0, but less avidly than ampicillin did.Neither ampicillin nor sulbactam inhibited myeloperoxidase activity. Sublethal concentrations of sulbactam had no significant effect on neutrophil killing of Staphylococcus aureus and Escherichia coli. Our results demonstrate a mechanism(s) by which ampicillin inhibits luminol-enhanced luminescence from stimulated neutrophils, namely, through scavenging of the oxidant(s) primarily responsible for the generation of luminescence.

Antibiotics Commonly Used to Treat Mastitis and Respiratory Burst of Bovine Polymorphonuclear Leukocytes

“…This suggestion was also made by Briheim and Dahlgren ( 1 ) . The lack of access of ampicillin to all cellular compartments in which ROS were generated has been mentioned previously by Gunther et al (12). The lack of effects at low concentrations and inhibitory effects at high and even supratherapeutic concentrations are in agreement with results that have been reported previously (6,8,25,31).…”

Protective role of ceftriaxone plus sulbactam with VRP1034 on oxidative stress, hematological and enzymatic parameters in cadmium toxicity induced rat model

“…But due to the presence of VRP1034 in ceftriaxone plus sulbactam, this combination showed synergistic effect that enhanced the free radical scavenging and chelating properties. Various studies reported that ceftriaxone and sulbactam individually showed free radical scavenging properties (Lapenna et al , 1995; Gunther et al , 1993). Our previous findings also showed that ceftriaxone plus sulbactam with VRP1034 was an effective drug for removal of arsenic intoxication in rats (Dwivedi et al , 2011).…”

“…Besides this property, cephalosporins are known as a thioether containing class of antibiotics, which are rather effective in preventing free radical-mediated oxidation of sulfhydryl groups in the antibiotics. Various studies reported that ceftriaxone and sulbactam individually showed free radical scavenging property (Lapenna et al , 1995; Gunther et al, 1993). It is well known that sulbactam acts as oxidant scavenger and inhibits in vitro neutrophil function (Santos and Arbo, 1989).…”

Modulatory effect of three antibiotics on uterus bovine contractility in vitro and likely therapeutic approaches in reproduction

“…The use of antibiotics was justified by their antimicrobial activity and for some of these (penicillins, quinolones, rifamycins, and macrolides) by their anti-inflammatory action and stimulatory effect on the immune system ( [22][23][24][25][26][27][28][29][30]; M. Albrizio et al, unpublished data, 2014). Moreover, the antibiotics, such as penicillins and quinolones, can also affect the oxidative state of the organism and the production of reactive oxygen species [30][31][32][33][34]. Several studies have reported that antibiotic therapy is able to directly modulate the contractility of smooth muscles [35][36][37][38][39] also.…”