Two diallyl sulphides derived from garlic inhibit meticillin-resistant Staphylococcus aureus infection in diabetic mice.
The inhibitory effect of diallyl sulphide (DAS) and diallyl disulphide (DADS) against meticillin-resistant Staphylococcus aureus (MRSA) infection in diabetic mice was studied. The influence of these agents on the plasma levels of fibronectin, C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-alpha), and on the activity of plasminogen activator inhibitor-1 (PAI-1), antithrombin III (AT-III) and protein C, in MRSA-infected diabetic mice was examined. To induce diabetes, mice were treated intraperitoneally with streptozotocin for 5 consecutive days. Ten clinical MRSA isolates obtained from infected patients were used in this study. Diabetic mice were infected by injecting 200 microl MRSA/PBS suspension containing 10(7) c.f.u. via the tail vein. At day 4 post-infection, 200 microl DAS or DADS was administrated twice orally with an interval of 12 h. Eight hours after each administration, the blood and organs of mice were collected. Results showed that DAS and DADS significantly decreased MRSA viability in the kidney (P<0.05), with administration of each agent twice showing a greater inhibitory effect than when given once (P<0.05). MRSA infection in diabetic mice significantly elevated the plasma levels of IL-6 and TNF-alpha (P<0.05). DAS or DADS given once did not affect the plasma levels of IL-6 and TNF-alpha (P>0.05); however, DAS or DADS given twice significantly decreased the plasma levels of both IL-6 and TNF-alpha (P<0.05). DAS and DADS treatments also significantly reduced the plasma levels of CRP, fibronectin and fibrinogen (P<0.05). DAS or DADS treatment did not affect PAI-1 activity (P>0.05), but DAS or DADS given twice significantly increased AT-III activity (P<0.05). DADS given twice elevated protein C activity (P<0.05). MRSA infection significantly increased malondialdehyde levels in the kidney and spleen (P<0.05), and these levels were significantly decreased by treatment with DAS or DADS (P<0.05). These data suggest that DAS and DADS could provide multiple protective functions against MRSA infection in diabetic mice.
Tsao
Shih-Ming
SM
Department of Infection, Chung Shan Medical University Hospital, Taichung City, Taiwan, Republic of China.
Liu
Wen-Hu
WH
Department of Nutritional Science, Chung Shan Medical University, Taichung City, Taiwan, Republic of China.
Yin
Mei-Chin
MC
Department of Nutritional Science, Chung Shan Medical University, Taichung City, Taiwan, Republic of China.
D000498:Allyl Compounds / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D000990:Antithrombin III / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D015169:Colony Count, Microbial; D016207:Cytokines / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D004195:Disease Models, Animal; D004220:Disulfides / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D005340:Fibrinogen / Q000032:analysis; D005353:Fibronectins / Q000097:blood; D005737:Garlic / Q000737:chemistry*; D006801:Humans; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D016106:Methicillin Resistance; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011486:Protein C / Q000032:analysis; D013154:Spleen / Q000473:pathology; D013203:Staphylococcal Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013311:Streptozocin; D013440:Sulfides / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*
D000498:Allyl Compounds; D000900:Anti-Bacterial Agents; D016207:Cytokines; D004220:Disulfides; D005353:Fibronectins; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D013440:Sulfides; D008315:Malondialdehyde; C028009:diallyl disulfide; D013311:Streptozocin; C038491:allyl sulfide; D000990:Antithrombin III; D005340:Fibrinogen; D002097:C-Reactive Protein