Influence of the Uvr repair system on the mutagenicity of antiparasitic drugs

Espinosa-Aguirre, J.J.; Santos, J. Ramírez; Nava, Carlos

doi:10.1016/0165-1218(89)90132-8

Cited by 11 publications

(5 citation statements)

References 14 publications

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“…The efficacy of chloroquine in the therapy of porphyria cutanea tarda (69) could be mediated by NO, which has been reported to inhibit heme synthesis (2). On the other hand, an increased NO production may account for some side effects of chloroquine, mainly observed after treatment with high doses of drug or during parenteral administration: inhibition of platelet aggregation (70), transient hypotension (71), reduced forearm vascular resistance (72), in vivo vasodilation (73), mutagenic effects (74), and neuropathies (75). If so, NOS inhibitors could be associated to high dosage chloroquine treatment to prevent the onset of several toxic effects of the drug.…”

Section: Discussionmentioning

confidence: 99%

Chloroquine stimulates nitric oxide synthesis in murine, porcine, and human endothelial cells.

Ghigo

Aldieri²,

Todde³

et al. 1998

J. Clin. Invest.

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Nitric oxide (NO) is a free radical involved in the regulation of many cell functions and in the expression of several diseases. We have found that the antimalarial and antiinflammatory drug, chloroquine, is able to stimulate NO synthase (NOS) activity in murine, porcine, and human endothelial cells in vitro: the increase of enzyme activity is dependent on a de novo synthesis of some regulatory protein, as it is inhibited by cycloheximide but is not accompanied by an increased expression of inducible or constitutive NOS isoforms. Increased NO synthesis is, at least partly, responsible for chloroquine-induced inhibition of cell proliferation: indeed, NOS inhibitors revert the drug-evoked blockage of mitogenesis and ornithine decarboxylase activity in murine and porcine endothelial cells. The NOS-activating effect of chloroquine is dependent on its weak base properties, as it is exerted also by ammonium chloride, another lysosomotropic agent.

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Section: Discussionmentioning

confidence: 99%

Chloroquine stimulates nitric oxide synthesis in murine, porcine, and human endothelial cells.

Ghigo

Aldieri²,

Todde³

et al. 1998

J. Clin. Invest.

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“…Positive mutagenic effects (either weak positive or positive) reported by several authors showed that CQ is capable of inducing mutation in the Salmonella strains TA97, TA97a, TA153 and TA1538, which are used to detects the frameshift mutations. During the mutagenicity assay, most studies did not find any significant differences in the revertant numbers either with or without metabolic activation [21,[28][29][30]. CQ also can interact with DNA and produce an intercalated complex that may induced frameshift mutation by shifting the reading frame [48,49].…”

Section: Reviewmentioning

confidence: 99%

“…While many authors have reported CQ to induce mutagenic effects in bacterial systems [ 20 – 22 , 24 , 27 – 30 , 32 ], few authors had found weak or no mutagenic associations in certain bacterial strains [ 14 , 23 , 25 , 28 , 31 – 33 ]. Positive mutagenic effects (either weak positive or positive) reported by several authors showed that CQ is capable of inducing mutation in the Salmonella strains TA97, TA97a, TA153 and TA1538, which are used to detects the frameshift mutations.…”

Section: Reviewmentioning

confidence: 99%

“…This indicates that CQ is a direct-acting mutagen. In addition to Salmonella strains, CQ showed mutagenic effects in Escherichia coli EE97, EE102, DG1669 strains, and WP2, WP2hcr, WP6 and WP67 strains [ 21 , 28 – 30 ]. CQ also can interact with DNA and produce an intercalated complex that may induced frameshift mutation by shifting the reading frame [ 48 , 49 ].…”

Section: Reviewmentioning

confidence: 99%

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Mutagenic, Genotoxic and Immunomodulatory effects of Hydroxychloroquine and Chloroquine: a review to evaluate its potential to use as a prophylactic drug against COVID-19

et al. 2020

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Hydroxychloroquine (HCQ) and Chloroquine (CQ) are two anti-malarial drugs that are now being extensively used by front-line healthcare workers and other common people as a prophylactic drug against the Corona Virus Disease − 19 (COVID-19) in India and as well as in many parts of the world. While only a few in vitro studies have pointed to some efficacy of these drugs as a prophylactic against COVID-19, to date, there are no clinical studies that have established any clinical efficacy of these drugs as a prophylactic. These drugs are commonly used for the treatment of Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) because of its immunomodulatory effects. Previously, we have evaluated the genetic toxicology of different drugs and chemicals including antimalarial drug CQ both in vitro and in vivo. Thus, we recognize the need to critically review the mutagenic, genotoxic, and immunomodulatory effects of these drugs, to find out whether it is safe to use as a prophylactic drug against COVID-19. Existing literature suggests that CQ can induce mutagenic and genotoxic effects in multiple test systems and both the drugs have immunomodulatory effects. There was no data available to evaluate the mutagenicity and genotoxicity for HCQ. However, during metabolism about 60% of both the drugs remain unchanged and about 40% of the drugs are metabolized into two metabolites, desethylchloroquine and bisdesethylchloroquine by the action of the cytochrome P450 (CYP) enzymes in the liver. Both HCQ and CQ are immunomodulatory drugs and have the potential to suppress normal immune system activation. In this review, we have elucidated the mechanism of immunomodulation by both HCQ and CQ and highlighted the mutagenic and genotoxic effects from the available literature. This article is written with the sole objective that the reader will be able to recognize the adverse effects of these drugs when consumed by healthy individuals as a prophylactic. Current literature indicates that healthy individuals should refrain from the use of these drugs until further investigation.

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“…Genotoxic effects of chloroquine on Escherichia coli was studied by Espinosa-Aguirre et al 33 . The result showed that chloroquine was genotoxic in Escherichia coli pol A+/pol A−.…”

Section: Structure Of Chloroquinementioning

confidence: 99%

Untitled

2012

IJPSR

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Influence of the Uvr repair system on the mutagenicity of antiparasitic drugs

Cited by 11 publications

References 14 publications

Chloroquine stimulates nitric oxide synthesis in murine, porcine, and human endothelial cells.

Chloroquine stimulates nitric oxide synthesis in murine, porcine, and human endothelial cells.

Mutagenic, Genotoxic and Immunomodulatory effects of Hydroxychloroquine and Chloroquine: a review to evaluate its potential to use as a prophylactic drug against COVID-19

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