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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 serum activities (mU/mL) of alanine aminotransferase (sALT) and γ-glutamyl transpeptidase (GGT) 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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f3-dddt-6-279: Effect of bifurans on serum activities (mU/mL) of alanine aminotransferase (sALT) and γ-glutamyl transpeptidase (GGT) 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: None of the tested bifurans caused any change in the activity of serum alanine aminotransferase, indicating no hepatotoxicity at the dosing regimen used. MRSA infection caused a significant elevation in the activity of the enzyme in serum (Figure 3). Bifurans were as effective as vancomycin in reducing the serum activity of the enzyme compared to infected untreated animals. Similar findings were reported for γ-GT, another enzyme investigated as a marker of disorders in many organs. Bifurans were more efficacious than vancomycin in reducing the elevated activity of the enzyme (Figure 3). The MRSA infection significantly elevated the serum urea level in mice, but compounds 1A and 1B were able to restore normal levels (Table 3), while vancomycin did not affect the urea level in infected animals.


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 serum activities (mU/mL) of alanine aminotransferase (sALT) and γ-glutamyl transpeptidase (GGT) 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

f3-dddt-6-279: Effect of bifurans on serum activities (mU/mL) of alanine aminotransferase (sALT) and γ-glutamyl transpeptidase (GGT) 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: None of the tested bifurans caused any change in the activity of serum alanine aminotransferase, indicating no hepatotoxicity at the dosing regimen used. MRSA infection caused a significant elevation in the activity of the enzyme in serum (Figure 3). Bifurans were as effective as vancomycin in reducing the serum activity of the enzyme compared to infected untreated animals. Similar findings were reported for γ-GT, another enzyme investigated as a marker of disorders in many organs. Bifurans were more efficacious than vancomycin in reducing the elevated activity of the enzyme (Figure 3). The MRSA infection significantly elevated the serum urea level in mice, but compounds 1A and 1B were able to restore normal levels (Table 3), while vancomycin did not affect the urea level in infected animals.

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