Synergistic effects of glutamine and ciprofloxacin in reduction of Pseudomonas aeruginosa-induced septic shock severity.
BACKGROUND
Systemic inflammatory response induced by over expressing inflammatory mediators is the main pathogenic mechanism of septic shock. Glutamine (Gln) has been demonstrated to inhibit pro-inflammatory cytokine release through enhanced heat shock protein (HSP) expression.


OBJECTIVE
To assess the effect of co-administration of Gln and antibiotic ciprofloxacin in reduction of septic shock severity caused by Pseudomonas aeruginosa in mice.


METHODS
Six- to eight-week old male BALB/c mice were used. At first, P. aeruginosa susceptibility to ciprofloxacin was determined. Then, 75% lethal dose (LD 75) of P. aeruginosa in a 10-day period was assessed. For determining survival rate, fifty mice were divided into 5 groups which included control (+), control (-), Gln, ciprofloxacin, and "glutamine+ciprofloxacin" group. All mice, except for control (-), were given an LD75 dose of P. aeruginosa and after 30 min each group received its special treatment: control (-) and control (+) groups received only 500λ phosphate buffer saline (PBS). Gln group received 500λ Ala-Gln, Cip group received 500λ ciprofloxacin. The Cip+Gln group received 500λ Gln and ciprofloxacin. Finally serum TNF-α, IL-10 and HSP-70 concentrations were measured and the severity of liver necrosis was examined.


RESULTS
Glutamine in combination with ciprofloxacin significantly increased survival rate and serum HSP-70 and IL-10 concentration and significantly decreased serum TNF-α concentration and the liver necrosis severity in comparison to control (+) group.


CONCLUSIONS
Gln has synergistic effects with ciprofloxacin in reduction of P. aeruginosa-induced septic shock.
Department of Microbiology; Faculty of Sciences, Zanjan Islamic Azad University, Zanjan, Iran.
Ebrahim
E
Mazloomi
Nima Hosseini
NH
Jazani
Mohammad
M
Sohrabpour
Behrouz
B
Ilkhanizadeh
Shahram
S
Shahabi
D000818:Animals; D002939:Ciprofloxacin / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005973:Glutamine / Q000627:therapeutic use*; D018840:HSP70 Heat-Shock Proteins / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D018840:HSP70 Heat-Shock Proteins; C556062:IL10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; D016753:Interleukin-10; D002939:Ciprofloxacin