Protein binding of chloroquine in the presence of aspirin.

Adelusi, S. A.; Salako, L.A.

doi:10.1111/j.1365-2125.1982.tb01402.x

Cited by 6 publications

(1 citation statement)

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“…These concentrations were much higher than were needed for inhibition of TB in MPs. However, human monocytic phagocytes concentrate CQ rapidly as much as 100-fold, and at the concentrations achieved in plasma during therapy of rheumatoid arthritis, they accumulate CQ at concentrations of 150 p.g/ml and higher (1,12). Furthermore, TB have acidic surfaces which could further increase CQ concentrations within infected phagolysosomes (14).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of tubercle bacilli in cultured human macrophages by chloroquine used alone and in combination with streptomycin, isoniazid, pyrazinamide, and two metabolites of vitamin D3

Crowle

May

1990

Antimicrob Agents Chemother

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Intracellular tubercle bacilli (TB) reside in vacuoles in infected human macrophages (MPs). The Tubercle bacilli (TB) in infected human macrophages (MPs) reside in vacuoles (4). These vacuoles might be phagolysosomes, which would be acidic and have several acid-dependent enzymes and activities (18). The presumed vacuolar acidity is thought to affect the activities of certain anti-TB drugs. It is supposed to decrease that of streptomycin (SM) (7) and increase that of pyrazinamide (PZA) (21,22,27).Chloroquine (CQ) is a drug which is widely used against malaria and certain kinds of chronic inflammatory diseases (3, 28). It is also used experimentally to study the acidic vacuoles of animal cells (16,24), because it is a lysosomotropic base (13, 28) which can increase the pH of these vacuoles and inhibit their acid-dependent activities (16,24). Thus, it inhibits malaria parasites by concentrating in the parasite's food vacuoles (lysosomes), raising their pH, and interfering with their digestive functions. This deprives the parasites of critical nutrients (13). Similarly, CQ can raise the pH of phagolysosomes in mammalian cells and affect their digestive functions (16,18,24). If TB do live in acid phagolysosomes in MPs and CQ can raise the pH of these vacuoles, then this drug should increase the anti-TB effectiveness of SM and lower that of PZA. This was tested in the experiments described here. While CQ enhanced the effectiveness of SM, as expected, it did not suppress that of PZA. Also, unexpectedly, it was itself able to inhibit TB in MPs, and it enhanced the anti-TB activity of another drug, isoniazid (INH), whose activity is not pH sensitive.(

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Section: Resultsmentioning

confidence: 99%