Elisa Pierpaoli1, Fiorenza Orlando2, Oscar Cirioni3, Oriana Simonetti4, Andrea Giacometti3, Mauro Provinciali5. 1. Advanced Technology Center for Aging Research, Scientific Technological Area, IRCCS-INRCA, Via Birarelli 8, Ancona 60121, Italy. 2. Experimental Animal Models for Aging Unit, Scientific Technological Area, IRCCS-INRCA, Via Birarelli 8, Ancona 60121, Italy. 3. Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Via Conca 10A, Ancona 60126, Italy. 4. Clinic of Dermatology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche - Ospedali Riuniti, Via Conca 10A, Ancona 60126, Italy. 5. Advanced Technology Center for Aging Research, Scientific Technological Area, IRCCS-INRCA, Via Birarelli 8, Ancona 60121, Italy; Experimental Animal Models for Aging Unit, Scientific Technological Area, IRCCS-INRCA, Via Birarelli 8, Ancona 60121, Italy. Electronic address: m.provinciali@inrca.it.
Abstract
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of skin and soft-tissue infection worldwide. An adequate immune response acts as a first line of defence against infections and therefore plays an essential role in the maintenance of health. Tocotrienols (T3s), the lesser known isomers of vitamin E, possess many biological properties and have been recognized as immunomodulators. PURPOSE: The aim of this study was to investigate whether the in vivo supplementation with a mixture of 87.1% δ- and 12.9% γ-T3s extract from seeds of Bixa orellana, (T3s) could be effective in increasing the effect of daptomycin (DAP) in a mouse model of wound infection due to MRSA. STUDY DESIGN/ METHODS: Bacteria were inoculated onto full-thickness wound on the dorsal side of BALB/c mice at 5 × 106 CFU per mouse. Mice were randomized into five groups: an uninfected group, an infected-untreated group, a T3s-pretreated group with no antibiotics given after challenge, a T3s-pretreated group plus DAP given after challenge, a group only given DAP after challenge. Main outcome measures were: bacterial load on the wounds, analysis of Natural Killer (NK) cytotoxicity, immunological phenotype and markers of tissue repair. RESULTS: Our results showed that bacterial load in wounds from mice receiving T3s or DAP alone was 1- or 3-log10 lower, respectively, compared with the infected-untreated group. T3s plus daptomycin showed the highest efficacy, achieving a 4-log10 decrease in bacterial load. This higher antimicrobial effect was associated with increased levels of NK cytotoxicity and markers of wound repair. CONCLUSION: These data suggest that treatment with T3s may be useful for the management of infected wounds as immune adjuvants in combination with DAP.
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of skin and soft-tissue infection worldwide. An adequate immune response acts as a first line of defence against infections and therefore plays an essential role in the maintenance of health. Tocotrienols (T3s), the lesser known isomers of vitamin E, possess many biological properties and have been recognized as immunomodulators. PURPOSE: The aim of this study was to investigate whether the in vivo supplementation with a mixture of 87.1% δ- and 12.9% γ-T3s extract from seeds of Bixa orellana, (T3s) could be effective in increasing the effect of daptomycin (DAP) in a mouse model of wound infection due to MRSA. STUDY DESIGN/ METHODS: Bacteria were inoculated onto full-thickness wound on the dorsal side of BALB/c mice at 5 × 106 CFU per mouse. Mice were randomized into five groups: an uninfected group, an infected-untreated group, a T3s-pretreated group with no antibiotics given after challenge, a T3s-pretreated group plus DAP given after challenge, a group only given DAP after challenge. Main outcome measures were: bacterial load on the wounds, analysis of Natural Killer (NK) cytotoxicity, immunological phenotype and markers of tissue repair. RESULTS: Our results showed that bacterial load in wounds from mice receiving T3s or DAP alone was 1- or 3-log10 lower, respectively, compared with the infected-untreated group. T3s plus daptomycin showed the highest efficacy, achieving a 4-log10 decrease in bacterial load. This higher antimicrobial effect was associated with increased levels of NK cytotoxicity and markers of wound repair. CONCLUSION: These data suggest that treatment with T3s may be useful for the management of infected wounds as immune adjuvants in combination with DAP.
Authors: David O Oluwole; Lucy Coleman; William Buchanan; Tao Chen; Roberto M La Ragione; Lian X Liu Journal: Pharmaceutics Date: 2022-05-09 Impact factor: 6.525
Authors: Nurul 'Izzah Ibrahim; Sok Kuan Wong; Isa Naina Mohamed; Norazlina Mohamed; Kok-Yong Chin; Soelaiman Ima-Nirwana; Ahmad Nazrun Shuid Journal: Int J Environ Res Public Health Date: 2018-10-25 Impact factor: 3.390