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Efficacy of two novel 2,2'-bifurans to inhibit methicillin-resistant Staphylococcus aureus infection in male mice in comparison to vancomycin.

El-Sayed WM, Hussin WA, Ismail MA - Drug Des Devel Ther (2012)

Bottom Line: Treatment with bifurans did not cause any toxicity.Treatment of MRSA-infected animals with bifurans resulted in significant reductions in the viable bacterial count in blood, liver, kidney, and spleen.Similar to vancomycin, bifurans ameliorated most of the previous effects.

View Article: PubMed Central - PubMed

Affiliation: Departments of Biological Sciences and Chemistry, King Faisal University, Al-Hofuf, Saudi Arabia. waelelhalawany@hotmail.com

ABSTRACT
The therapeutic efficacy of two novel bifurans and vancomycin in an animal model of a methicillin-resistant Staphylococcus aureus (MRSA) infection was compared. Adult male CF-1 mice (25-35 g) were intraperitoneally injected with 200 μL/mouse containing 10(7) cell-forming units of MRSA. After 16 hours, animals were treated with 110 mg/kg of vancomycin, or 5 mg/kg of mononitrile bifuran (1A) or monocationic bifuran (1B) and killed after 8 hours. Treatment with bifurans did not cause any toxicity. Treatment of MRSA-infected animals with bifurans resulted in significant reductions in the viable bacterial count in blood, liver, kidney, and spleen. Colonies recovered from livers and kidneys of mice injected with 1A or 1B lost the initial resistance pattern and became susceptible to methicillin and ciprofloxacin. MRSA elevated the serum urea level and activities of alanine aminotransferase and γ-glutamyl transpeptidase. MRSA also elevated the hepatic level of malondialdehyde, and serum levels of tumor necrosis factor and interleukin-6. MRSA also reduced the glutathione content and activities of catalase and glutathione S-transferase in liver. Similar to vancomycin, bifurans ameliorated most of the previous effects. Compound 1B was superior to 1A, and sometimes both provided better antistaphylococcal agents than vancomycin against MRSA pathogenesis. The present findings along with our previous studies support further evaluation of the efficacy of these bifurans in clinical studies.

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Related in: MedlinePlus

Effect of bifurans on hepatic activities (nmol/minute/mg) of glutathione reductase (GR) and glutathione peroxidase (GPx) in MRSA-infected animals. Notes: Data are expressed as means ± standard error of mean, n = 5. aSignificant difference (P < 0.05) compared to uninfected control group; bsignificant difference (P < 0.05) compared to untreated infected group. Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.
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f5-dddt-6-279: Effect of bifurans on hepatic activities (nmol/minute/mg) of glutathione reductase (GR) and glutathione peroxidase (GPx) in MRSA-infected animals. Notes: Data are expressed as means ± standard error of mean, n = 5. aSignificant difference (P < 0.05) compared to uninfected control group; bsignificant difference (P < 0.05) compared to untreated infected group. Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.

Mentions: Challenging animals with bacteria elevated GSH reductase (GR) and GSH peroxidase (GPx) activities in liver. Treating infected animals with vancomycin or any of the bifurans under study significantly reduced the activities of the enzymes to normal control levels (Figure 5). Treating uninfected mice with compound 1B elevated GPx activity compared to control mice. None of the treatments significantly affected superoxide dismutase activity in liver (Table 4). Bacterial infection in mice resulted in a significant reduction in catalase activity compared to control uninfected mice. With the exception of this reduction in catalase activity, none of the treatments significantly affected hepatic catalase activity (Table 4). Challenging mice with bacteria also resulted in a significant reduction in GST activity compared to control. On treating infected mice with vancomycin, enzyme activity was elevated compared to infected untreated animals. Treatment of infected mice with either bifuran investigated did not significantly affect the enzyme activity (Table 4).


Efficacy of two novel 2,2'-bifurans to inhibit methicillin-resistant Staphylococcus aureus infection in male mice in comparison to vancomycin.

El-Sayed WM, Hussin WA, Ismail MA - Drug Des Devel Ther (2012)

Effect of bifurans on hepatic activities (nmol/minute/mg) of glutathione reductase (GR) and glutathione peroxidase (GPx) in MRSA-infected animals. Notes: Data are expressed as means ± standard error of mean, n = 5. aSignificant difference (P < 0.05) compared to uninfected control group; bsignificant difference (P < 0.05) compared to untreated infected group. Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3472655&req=5

f5-dddt-6-279: Effect of bifurans on hepatic activities (nmol/minute/mg) of glutathione reductase (GR) and glutathione peroxidase (GPx) in MRSA-infected animals. Notes: Data are expressed as means ± standard error of mean, n = 5. aSignificant difference (P < 0.05) compared to uninfected control group; bsignificant difference (P < 0.05) compared to untreated infected group. Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.
Mentions: Challenging animals with bacteria elevated GSH reductase (GR) and GSH peroxidase (GPx) activities in liver. Treating infected animals with vancomycin or any of the bifurans under study significantly reduced the activities of the enzymes to normal control levels (Figure 5). Treating uninfected mice with compound 1B elevated GPx activity compared to control mice. None of the treatments significantly affected superoxide dismutase activity in liver (Table 4). Bacterial infection in mice resulted in a significant reduction in catalase activity compared to control uninfected mice. With the exception of this reduction in catalase activity, none of the treatments significantly affected hepatic catalase activity (Table 4). Challenging mice with bacteria also resulted in a significant reduction in GST activity compared to control. On treating infected mice with vancomycin, enzyme activity was elevated compared to infected untreated animals. Treatment of infected mice with either bifuran investigated did not significantly affect the enzyme activity (Table 4).

Bottom Line: Treatment with bifurans did not cause any toxicity.Treatment of MRSA-infected animals with bifurans resulted in significant reductions in the viable bacterial count in blood, liver, kidney, and spleen.Similar to vancomycin, bifurans ameliorated most of the previous effects.

View Article: PubMed Central - PubMed

Affiliation: Departments of Biological Sciences and Chemistry, King Faisal University, Al-Hofuf, Saudi Arabia. waelelhalawany@hotmail.com

ABSTRACT
The therapeutic efficacy of two novel bifurans and vancomycin in an animal model of a methicillin-resistant Staphylococcus aureus (MRSA) infection was compared. Adult male CF-1 mice (25-35 g) were intraperitoneally injected with 200 μL/mouse containing 10(7) cell-forming units of MRSA. After 16 hours, animals were treated with 110 mg/kg of vancomycin, or 5 mg/kg of mononitrile bifuran (1A) or monocationic bifuran (1B) and killed after 8 hours. Treatment with bifurans did not cause any toxicity. Treatment of MRSA-infected animals with bifurans resulted in significant reductions in the viable bacterial count in blood, liver, kidney, and spleen. Colonies recovered from livers and kidneys of mice injected with 1A or 1B lost the initial resistance pattern and became susceptible to methicillin and ciprofloxacin. MRSA elevated the serum urea level and activities of alanine aminotransferase and γ-glutamyl transpeptidase. MRSA also elevated the hepatic level of malondialdehyde, and serum levels of tumor necrosis factor and interleukin-6. MRSA also reduced the glutathione content and activities of catalase and glutathione S-transferase in liver. Similar to vancomycin, bifurans ameliorated most of the previous effects. Compound 1B was superior to 1A, and sometimes both provided better antistaphylococcal agents than vancomycin against MRSA pathogenesis. The present findings along with our previous studies support further evaluation of the efficacy of these bifurans in clinical studies.

Show MeSH
Related in: MedlinePlus