RESUMO
Diabetic patients are more susceptible to developing wound infections resulting in poor and delayed wound healing. Bacteriophages, the viruses that target-specific bacteria, can be used as an alternative to antibiotics to eliminate drug-resistant bacterial infections. Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) are among the most frequently identified pathogens in diabetic foot ulcers (DFUs). The aim of this study was assessment of bacteriophage and gentamicin combination effects on bacterial isolates from DFU infections. Specific bacteriophages were collected from sewage and animal feces samples and the phages were enriched using S. aureus and P. aeruginosa cultures. The lytic potential of phage isolates was assessed by the clarity of plaques. We isolated and characterized four lytic phages: Stp2, Psp1, Stp1, and Psp2. The phage cocktail was optimized and investigated in vitro. We also assessed the effects of topical bacteriophage cocktail gel on animal models of DFU. Results revealed that the phage cocktail significantly reduced the mortality rate in diabetic infected mice. We determined that treatment with bacteriophage cocktail effectively decreased bacterial colony counts and improved wound healing in S. aureus and P. aeruginosa infections, especially when administrated concomitantly with gentamicin. The application of complementary therapy using a phage cocktail and gentamicin, could offer an attractive approach for the treatment of wound diabetic bacterial infections.
Assuntos
Bacteriófagos , Diabetes Mellitus , Infecções por Pseudomonas , Infecções Estafilocócicas , Humanos , Camundongos , Animais , Staphylococcus aureus , Pseudomonas aeruginosa , Gentamicinas/farmacologia , Gentamicinas/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções por Pseudomonas/terapia , Infecções por Pseudomonas/microbiologia , Modelos Animais de Doenças , Diabetes Mellitus/tratamento farmacológicoRESUMO
BACKGROUND: Peripheral neuropathy is a common complication of diabetes mellitus. It has been shown that hyperglycemia may contribute to its development but the exact pathophysiology underlying this complication is not fully understood. Since oral magnesium supplementation can normalize hyperglycemia induced by diabetes in rats, this study was designed to examine the effect of oral magnesium administration on thermal hyperalgesia in streptozocin-induced diabetic rats. MATERIAL AND METHODS: Twenty-four male adult wistar rats were divided equally into control, magnesium-treated control, diabetic and magnesium-treated diabetic groups. In magnesium-treated diabetic rats, magnesium sulfate (10g/l) was added into the drinking water once diabetes was established (10 days after STZ injection) and continued for 8 weeks. Mg-treated control animals received magnesium sulfate in the same dose and over the same time period. The other two groups; control and diabetic animals, only received tap water. At the end of the 8 weeks, thermal pain threshold was assessed by tail flick test and magnesium and glucose plasma levels were measured in all groups. RESULT: A significant decrease (p<0.001) in thermal pain threshold and plasma magnesium levels and an increase in plasma glucose levels (p<0.001) were seen in diabetic rats 8 weeks after diabetes induction. After 8 weeks of oral magnesium, thermal hyperalgesia was normalized and plasma magnesium and glucose levels were restored towards normal. CONCLUSION: It is concluded that oral magnesium administration given at the time of diabetes induction may be able to restore thermal hyperalgesia, magnesium deficiency and hyperglycemia and in diabetic rats.