12+

INTERACTION BETWEENSOME ANTIBIOTICS AND ANTIOXIDANTS

Introduction: The bactericidal action of many antibacterial agents has a common mechanism associated with the generation of hydroxyl radicals and the activation of oxidative stress. This is confirmed by the ratio between the degree of bactericidal effect and the level of hydroxyl radicals. The study of the effect of antioxidants on the antibacterial activity of chemotherapeutic agents can open new prospects for improving the treatment of infectious diseases.

Objectives: Study of the effect of antioxidants on the activity of chemotherapeutic agents in relation to opportunistic bacteria

Methods: The study examined the interaction of antibiotics (gentamicin, ciprofloxacin, ceftazidime) and antioxidants (ascorbic acid, N-acetylcysteine, methylethylpyridinol) in vitro and in vivo. We conducted a dynamic study of the effect of antioxidants at concentrations of 0.5, 1, 2 and 4 mM on the activity of antibacterial agents in vitro for three strains of Klebsiella pneumoniae and three strains of Escherichia coli. The effect of antioxidants on the effectiveness of antibacterial therapy was studied in Wistar rats with experimental bacterial peritonitis.

Results and discussion: In vitro studies have shown that all antioxidants reduce the activity of gentamicin. Methyl ethylpyridinol increases the effect of ciprofloxacin, ceftazidime. Ascorbic acid enhances the action of ceftazidime. Ascorbic acid, methylethylpyridinol and N-acetylcysteine (80 mg / kg) reduce the antibacterial activity of gentamicin (30 mg / kg) and ciprofloxacin (50 mg / kg) and do not change the intensity of peroxidation processes in combination with these antibacterial agents under experimental infection caused by K. pneumoniae. These antioxidants reduce the prooxidant effect of ciprofloxacin (50 mg / kg), without affecting its antibacterial activity in escherichiosis peritonitis. Ascorbic acid, methylethylpyridinol and N-acetylcysteine (80 mg / kg) do not reduce the nephrotoxic effect of gentamicin (30 mg / kg).

Conclusion: Antioxidants have anmultidirectional effect on the efficacy of antibacterial agents in vitro and under experimental bacterial peritonitis. Combination of antibiotics with antibacterial agents should be accompanied by preliminary in vitro studies. The rational combination of antibacterial agents and antioxidants increases the effectiveness of anti-infective chemotherapy and prevents the formation of resistant strains.

Иллюстрации

Table 1.  Antioxidants and antibiotics

Table 2. Interaction between antibacterial agents and antioxidants in vitro

Note. Antagonism: A ++ - within 24 hours of incubation; A + - in most cases, the dependence on the concentration of the antioxidant may be absent; A - episodic development of culture is higher than control, dependence on antioxidant concentration may be absent; 0 - no influence, the development of culture does not change, or there are point changes with respect to control. Synergy: S - episodic development of culture below control, dependence on antioxidant concentration may be absent; S + - in most cases, the dependence on the concentration of the antioxidant may be absent; S ++ - within 24 hours of incubation.

Table 3.  Biochemical indices of rats with bacterial peritonitis caused by Escherichia coli (with gentamicin administration)

Table 4. Biochemical indices of rats with bacterial peritonitis caused by Klebsiella pneumoniae (with gentamicinadministration)

 

Table 5. Biochemical indices of rats with bacterial peritonitis caused by Escherichia coli (with ciprofloxacinadministration)

Table 6. Biochemical indices of rats with bacterial peritonitis caused by Klebsiella pneumoniae(with ciprofloxacinadministration)

Table 7. Biochemical indices of rats with bacterial peritonitis caused by Escherichia coli (with ceftazidimeadministration)

Table 8. Biochemical indices of rats with bacterial peritonitis caused by Klebsiella pneumoniae (with ceftazidimeadministration)

DOI: 10.18413/2313-8971-2017-3-4-100-112
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