Effects of primaquine and chloroquine on oxidative stress parameters in rats

Giovanella, Francianne; Ferreira, Gabriela K.; Prá, Samira Dal Toé De; Carvalho-Silva, Milena; Gomes, Lara M.; Scaini, Giselli; Gonçalves, Renata C.; Michels, Monique; Galant, Letícia Selinger; Longaretti, Luiza Martins; Dajori, Ana Luiza F; Andrade, Vanessa Moraes de; Dal‐Pizzol, Felipe; Streck, Emílio L.; Souza, Renan P.

doi:10.1590/0001-3765201520140637

Cited by 26 publications

(21 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, prolonged duration of chloroquine administration led to retinopathy in rats [29,30] . More recently, it was proved that chloroquine increased the oxidative stress as it might adversely affect the DNA in rat brain [31] .…”

Section: Differentmentioning

confidence: 99%

Does Oral Chloroquine Affect the Hippocampus in Rats? A Clue to Chloroquine Induced Neuropsychiatric Adverse Effects

Al-Neklawy

2020

Ain Shams Medical Journal

View full text Add to dashboard Cite

Background: Chloroquine is widely used in medicine. The main indication for its usage is treatment of malaria. Reports about psychiatric side effects of chloroquine are rare. However, the list of recorded chloroquine induced neuropsychiatric disorders shows wide range of symptoms. Aim of the work: In this study, the effect of oral chloroquine on the hippocampus of rats was assessed. Material and methods: Twenty seven male adult albino rats were randomly divided into four groups. Group I (control group): nine rats were divided into I-a and I-b subgroups. Group II (chloroquine for two weeks): six rats received 4ml of distilled water solution/day containing chloroquine in a dose of 80 mg/kg bwvia oral gavage for two weeks. Group III (chloroquine for three weeks): six rats received chloroquine as in group II for three weeks. Group IV (chloroquine for four weeks): six rats received chloroquine as in group II for four weeks. After sacrifice, the hippocampi were retrieved, fixed, and processed for paraffin sections. H&E and Bielschowsky silver stains were applied and immunehistochemical staining for GFAP was performed to examine the distribution of astrocytes. Results: Examination of different regions of the hippocampal formation revealed dark, shrunken cells, with pyknotic nuclei and pericellular spaces in all treated groups. Neurofibrillary tangles were also seen in some stained sections. Moreover, an increase in the density of astrocytes was also observed. Morphometrically, there was a decrease in the thickness of both pyramidal and granular layers of cornu ammonis and dentate gyrus respectively in all treated groups as compared with control group. All these changes appeared in group II, and were clearer in both groups III and IV. Conclusion: It was concluded that oral administration of chloroquine caused duration dependent neuronal damage in the hippocampus of rats giving a possible explanation for chloroquine induced neuropsychiatric adverse effects.

show abstract

Section: Differentmentioning

confidence: 99%

Does Oral Chloroquine Affect the Hippocampus in Rats? A Clue to Chloroquine Induced Neuropsychiatric Adverse Effects

Al-Neklawy

2020

Ain Shams Medical Journal

View full text Add to dashboard Cite

show abstract

“…Considering that both ATM and p53 are sensitive to oxidative stress, (59, 60) these findings indicate that activation of the ATM-p53 signaling by CHQ might be triggered by oxidative DNA damage. Interestingly, while activating key mediators of DDR, CHQ has an intrinsic repair-inhibiting activity manifest in different types of normal and neoplastic cells in vitro (30, 58) and in vivo (61). Although the exact mechanisms of CHQ–mediated inhibition of DNA repair remain unknown, they are likely to reflect the causative relationship between impaired autophagy and deficient DNA repair (62).…”

Section: Functional Pleiotropy Of Chloroquine: the Balance Of Good Anmentioning

confidence: 99%

Re-purposing Chloroquine for Glioblastoma: Potential Merits and Confounding Variables

2018

View full text Add to dashboard Cite

There is a growing evidence that antimalarial chloroquine could be re-purposed for cancer treatment. A dozen of clinical trials have been initiated within the past 10 years to test the potential of chloroquine as an adjuvant treatment for therapy–refractory cancers including glioblastoma, one of the most aggressive human cancers. While there is considerable evidence for the efficacy and safety of chloroquine the mechanisms underlying the tumor suppressive actions of this drug remain elusive. Up until recently, inhibition of the late stage of autophagy was thought to be the major mechanism of chloroquine-mediated cancer cells death. However, recent research provided compelling evidence that autophagy-inhibiting activities of chloroquine are dispensable for its ability to suppress tumor cells growth. These unexpected findings necessitate a further elucidation of the molecular mechanisms that are essential for anti-cancer activities of CHQ. This review discusses the versatile actions of chloroquine in cancer cells with particular focus on glioma cells.

show abstract

“…CQ also can interact with DNA and produce an intercalated complex that may induced frameshift mutation by shifting the reading frame [48,49]. This also indicates it's DNA damage and inhibition of DNA repair potentials reported by several authors [19,34,38,39,45]. CQ is further reported to induce sex-linked recessive lethal mutation in Drosophila melanogaster [26].…”

Section: Reviewmentioning

confidence: 95%

“…CQ has also been reported to induce oxidative stress in animal models [51]. For instance, when CQ administered intraperitoneally in rats, it induced DNA breaks in the kidney within 1 to 2 weeks and in the liver within 2 to 3 weeks [45]. Chromosomal Aberrations (CA) have also been long considered to be a predictor for cancer.…”

Section: Reviewmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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.

show abstract

Effects of primaquine and chloroquine on oxidative stress parameters in rats

Cited by 26 publications

References 42 publications

Does Oral Chloroquine Affect the Hippocampus in Rats? A Clue to Chloroquine Induced Neuropsychiatric Adverse Effects

Does Oral Chloroquine Affect the Hippocampus in Rats? A Clue to Chloroquine Induced Neuropsychiatric Adverse Effects

Re-purposing Chloroquine for Glioblastoma: Potential Merits and Confounding Variables

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

Contact Info

Product

Resources

About