Oral Manifestations of Chloroquine and Hydroxychloroquine: Differential Diagnoses

Chloroquine phosphate and hydroxychloroquine sulfate are organic compounds, known as aminoquinolines for containing an amino group attached to a quinoline ring. They have been used since World War II as antimalarial agents. The article search that made up this review was carried out in the PubMed database, using the keywords “Chloroquine”, “Hydroxychloroquine”, and “Oral Manifestations”, in the period including 2005 to 2020. The sample size was 7 female patients aged 40 to 66 years, with an age predominance of between 50 and 60 years old. The predominant lesion site was the hard palate with 6 cases. To reach the diagnosis of pigmented lesions in the oral cavity, meticulous anamnesis prior to physical examination is extremely important. In this pandemic and post-pandemic period, a more detailed investigation of the medications used by the patient in recent periods, such as chloroquine and hydroxychloroquine are essential to detect if the lesion was possibly caused by these drugs.

Autophagy inhibition by chloroquine sensitizes HT-29 colorectal cancer cells to concurrent chemoradiation

AIM:To investigate whether the inhibition of autophagy by chloroquine(CQ)sensitizes rectal tumors to radiation therapy(RT)or concurrent chemoradiation(chemoRT).METHODS:In vitro,HCT-116 and HT-29 colorectal cancer(CRC)cell lines were treated as following:(1)PBS;(2)CQ;(3)5-fluorouracil(5-FU);(4)RT;(5)CQ and RT;(6)5-FU and RT;(7)CQ and 5-FU;and(8)5-FU and CQ and RT.Each group was then exposed to various doses of radiation(0-8 Gy)depending on the experiment.Cell viability and proliferative capacity were measured by3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and clonogenic assays.Clonogenic survivalcurves were constructed and compared across treatment groups.Autophagy status was determined by assessing the LC3-Ⅱto LC3-Ⅰratio on western blot analysis,autophagosome formation on electron microscopy and identification of a perinuclear punctate pattern with GFPlabeled LC3 on fluorescence microscopy.Cell cycle arrest and cell death were evaluated by FACS and AnnexinⅤanalysis.All experiments were performed in triplicate and statistical analysis was performed by the student’s t test to compare means between treatment groups.RESULTS:RT(2-8 Gy)induced autophagy in HCT-116and HT-29 CRC cell lines at 4 and 6 h post-radiation,respectively,as measured by increasing LC3-Ⅱto LC3-Ⅰratio on western blot.Additionally,electron microscopy demonstrated autophagy induction in HT-29 cells24 h following irradiation at a dose of 8 Gy.Drug treatment with 5-FU(25μmol/L)induced autophagy and the combination of 5-FU and RT demonstrated synergism in autophagy induction.CQ(10μmol/L)alone and in combination with RT effectively inhibited autophagy and sensitized both HCT-116 and HT-29 cells to treatment with radiation(8 Gy;P<0.001 and 0.00001,respectively).Significant decrease in clonogenic survival was seen only in the HT-29 cell line,when CQ was combined with RT at doses of 2 and 8 Gy(P<0.5 and P=0.05,respectively).There were no differences in cell cycle progression or Annexin V staining upon CQ addition to RT.CONCLUSION:Autophagy inhibition by CQ increases CRC cell sensitivity to concurrent treatment with 5-FU and RT in vitro,suggesting that addition of CQ to chemoRT improves CRC treatment response.

Effects of Chloroquine on GFAP, PCNA and Cyclin D1 in Hippocampus and Cerebral Cortex of Rats with Seizures Induced by Pentylenetetrazole

The effects of chloroquine on glial fibrillary acidic protein （GFAP）, proliferation cell nuclear antigen （PCNA） and Cyclin D1 in hippocampus and cerebral cortex of rats with seizures induced by pentylenetetrazole （PTZ） were observed in the present study. Forty-eight male adult Sprague-Dawley （SD） rats were randomly divided into control group, chloroquine intervening group, and PTZ group. The behavior and electroencephalogram （EEG） were observed and recorded. GFAP and PCNA were examined with immunohistochemistry. The content of Cyclin D1 in hippocampus and cerebral cortex was inspected with Western blot. The results showed no seizure activity in the control group, severe seizure activity in the PTZ group （Ⅳ - Ⅴ degree）, and slight seizure activity （ Ⅰ -- Ⅲ degree） in the chloroquine intervening group （P〈0.05）. EEG recordings showed no epileptic spikes in the control group, high amplitude with fast frequency in the PTZ group, low amplitude and slow frequency in the chloroquine intervening group. The expression of GFAP and the positive index of PCNA in the PTZ group were higher than those of control group （P 〈0.05 and P〈0.01, respectively）. No differences in GFAP expression and PCNA index were observed between chloroquine intervening and control groups （P〉0.05）. The content of Cyclin D1 in hippocampus and cerebral cortex was significantly higher in the PTZ group than in control and chloroquine intervening groups （P〈 0.05）. Therefore, it is considered that chloroquine, by inhibiting the functions and proliferation of glial cells in the hippocampus and cerebral cortex, can alleviate the seizure activities. These results suggest that chloroquine may be an ideal anticonvulsant in preventing and treating epilepsy.

Chloroquine Relieves Acute Lung Injury in Rats with Acute Hemorrhagic Necrotizing Pancreatitis

Summary： This study preliminarily investigated the mechanism by which chloroquine （CQ） relieves acute lung injury （ALI） complicated in acute hemorrhagic necrotizing pancreatitis （AHNP）. Sixty male Wistar rats were randomized into sham-operated group （group A, n=10）, AHNP group （group B, n=10）, L-arginine-treated group （group C, n=10）, L-N-nitro-L-arginine methyl ester （NAME）-treated group （group D, n=10）, CQ-treated group （group E, n=10） and CQ＋L-NAME-treated group （group F, n=10）. TLR4 expression was measured by using real time-PCR and Western blotting respectively. The results showed that, in the group B, the expression of TLR4 and the levels of TNF-α and IL-6 in the lungs were significantly increased, and the nitric oxide （NO） concentration was reduced, as compared with those in the group A （P〈0.05 or P〈0.01）. Lung injury was aggravated with the increased expression of TLR4. When the inhibitor and stimulator of TLR4, namely L-Arg and L-NAME, were added respectively, lung injury was correspondingly relieved or aggravated （P〈0.05 or P〈0.01）. In the group E, TLR4 expres- sion was substantially lower and NO concentration higher than those in the group B （P〈0.05 or P〈0.01）. However, in the group F, NO concentration was markedly decreased, and the inhibitory effect of CQ on TLR4 expression and the relief of lung injury were weakened when compared with those in the group E （P〈0.05 or P〈0.01）. It was concluded that TLR4 may play an important role in the pathogenesis and development of ALl complicated in AHNP. CQ could relieve ALl by decreasing the TLR4 expression and increasing the NO release.

Adjuvant effect of a synthetic Aluminium-Magnesium Silicate on chloroquine phosphate, against Plasmodium berghei

Effect a synthetic Aluminium-Magnesium Silicate (AMS) has on chloroquine was tested. Thirty, Plasmodium berghei-infected mice, in three experimental groups (7 mg/kg, 5 mg/kg and 3 mg/kg) of 10 mice each, were treated. Two subgroups, in each experiment, were treated with chloroquine and with a chloroquine-AMS drug formulation, respectively. Five of the infected mice served as controls. Parasitaemia (%), Haemoglobin concentration (Hb), Red Blood Cells (RBC), rectal temperature and body weight were assessed. Parasitaemia of subgroups treated at 7 mg/kg were higher than that of the control. Also, at 7 mg/kg, there was mortality with chloroquine (20%) and with the chloroquine-AMS drug (80%). At 5 mg/kg and 3 mg/kg, the AMS significantly (P < 0.05) improved ability of chloroquine to reduce plamodial parasitaemia, from 2.46 ± 0.21 to 1.57 ± 0.25 and from 3.82 ± 0.06 to 2.12 ± 0.08. It also significantly (P < 0.05) improved means of Hb and RBC from 12.25 ± 0.27 and 88.99 ± 5.72 to 12.68 ± 0.18 and 92.91 ± 4.01 and from 10.18 ± 3.00 and 63.39 ± 18.02 to 12.98 ± 0.47 and 95.23 ± 5.32. Body weight increased at 5 mg/kg, from 29.06 ± 1.95 to 32.66 ± 2.10 kg (P < 0.05) while at 3 mg/kg, rectal temperature reduced from 37.35 ± 0.32 to 36.84oC ± 0.23oC (P < 0.05). These results suggest, AMS worsened chloroquine toxicity at 7 mg/kg but potentiated its antiplasmodial activities at the lower doses.

Role of Nociceptive Arcuate Nucleus Neurons in Chloroquine-induced Pruritic Behaviors in Mice

Despite its clinical importance, the underlying central mechanisms of pruritic behaviors are poorly understood. To investigate the role of nociceptive arcuate nucleus neurons in chloro-quine-induced pruritic behaviors in mice, we tested the effect of arcuate nucleus neurons and interscapular brown adipose tissue (IBAT) on itch produced by intradermal injection of chloroquine in the nape of the neck. Our results provide several lines of evidence for an important role of nociceptive arcuate nucleus neurons in chloroquine-induced pruritic behavior: (1) Intradermal microinjection of chloro-quine resulted in a dramatic increase in itch behaviors accompanied by the activation of c-Fos positive neurons in arcuate nucleus; (2) Microinjection of chloroquine significantly increased IBAT temperature in the mice. These findings suggested that chloroquine-induced pruritic behaviors were associated with the activity of nociceptive arcuate nucleus neurons.

Comparative study of chloroquine and quinine on malaria rodents and their effects on the mouse testis

Objective:To evaluate the effects of quinine and chloroquine against mole mice infected with Plasmodium berghei and their adverse effects on the mice testes.Methods:In this study,48 adult male mice,(20-23 g).aged 8 to 12 weeks were divided into four groups.This study was carried out from December 2009 until May 2010 in the School of Public Health,Tehran University of Medical Sciences.Results:The results showed that 58.33%of mice treated with chloroquine were completely recovered.Parasitemia was 4%on day 8 when compared to that on day 0,whereas it was 9%on day 9.There was no orchitis found in this group.The mortality of mice after exposing to quinine on day 5 was 8.3%,whereas from day 10 to day 14 it was 91.7%.We found 73%orchitis occurred in quinine treated group.There was a significant difference between quinine and chloroquine effects on the parasite and also mice testes(P<0.05).Conclusions:In this study,It can be concluded that male mice have full resistance to the quinine.Quinine does not only make male mice recover completely,but also cause inflammation on mice testicles tissue.

Identification of antimalarial targets of chloroquine by a combined deconvolution strategy of ABPP and MS-CETSA

Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an indispensable role, however, its mechanism of action(MoA) is not fully understood.Methods: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling(ABPP) and mass spectrometry-coupled cellular thermal shift assay(MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays.Results: We developed a novel clickable, photo-affinity chloroquine analog probe(CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photocrosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods.Conclusions: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled(ABPP)and label-free(MS-CETSA) methods.

Nano chloroquine delivery against Plasmodium berghei NK65 induced programmed cell death in spleen

Objective:To compare the protective effects of chitosan-trypolyphosphate(CS-TPP) nanoparticle conjugated chloroquine(CQ) with effect of CQ alone on the reversal of splenic damages and induction of apoptosis.Methods:Different researches have been carried out to explore the potential role of chitosan based drug delivery system against parasitic diseases.After successive Plasmodium berghei NK65 parasiste infection by intraperitoneal injection in Swiss mice and subsequent parasite development,the ROS generation,anti-apoptotic and pro apoptotic protein levels in spleen were measured.To analyze caspases,flow cytometry study was performed with annexin 桋-FITC and with PI staining.Results:The results revealed that ROS mediated caspase 3 and 9 activation and the induction of apoptosis occurred during the parasitic infection.However,CS-TPP conjugated CQ was relatively better in reversing the splenic damage compared with similar effects of CQ alone.Conclusions:This study indicates that Plasmodium berghei NK65 induces apoptosis in the spleen.The study further shows that CS-TPP nanoparticles conjugation with CQ have positive influence on the recovery of damaged host's system towards maintenance of normal homeostasis,and this is shown to be selective to CS-TPP conjugated CQ treated animals only.

Antimalarial activity of Ageratum conyzoides in combination with chloroquine and artesunate

Objective:To determine the suppressive and curative activity of aqueous leaf extract of Ageratum conyzoides(A.conyzoides) in combination with chloroquine and artesunate, respectively against Plasmodium berghei infection in mice.Methods:Using malaria(Plasmodium berghei) infected albino mice of both sexes,aqueous extracts of A.conyzoides in combination with chloroquine and artesunate were tested for antimalarial activity,respectively.Four-day suppressive test and Rane’s curative test were carried out.Results:Suppressive tests showed significant dose dependent reduction in parasitemia level produced by the extract-chloroquine and extract-artesunate combinations.Suppressive activities of both extract-drug combinations were greater than the individual drugs alone.Extract-chloroquine(100:5) produced the highest suppressive effect(98%suppression).Curative tests showed absolute survival in two extract-drug combinations.Two extract-drug combinations produced higher curative effects than the individual drugs alone.The highest dose combinations of extract-chloroquine(100:5) and extract-artesunate(100:5) produced absolute parasitemia clearance(cure) in the infected mice. Conclusions:The study indicated that aqueous extract of A.conyzoides had the ability to potentiate the antimalarial activity of chloroquine and artesunate against induced plasmodiasis in mice.It contributes a lot in the malaria endemic and poverty stricken tropics.

Combination of kaempferol and chloroquine induces glioma cell death via expansion and subsequent rupture of lysosomes

OBJECTIVE Chloroquine is considered as a potential chemotherapy and radiotherapy sensitizer,but the anticancer effect of chloroquine alone is limited.Since we found that the flavonoid kaempferol effectively sensitizes glioma cells to chloroquine-mediated cell death,we investigated the underlying mechanisms of glioma cell death induced by the combination of kaempferol and chloroquine.METHODS To examine the effect of kaempferol and/or chloroquine on various glioma cells,cell viability assay using calcein-AM and EthD-1was performed.The changes in the lysosomal structures following treatment with kaempferol and/or chloroquine were observed by electron microscopy and fluorescence microscopy using acridine orange or Lyso-tracker Red.The changes in cathepsin D proteins were analyzed by Western blotting,immunocytochemistry,and fluorescence microscopy using BODIPY FL-pepstatin.RESULTS Treatment with subtoxic doses of chloroquine,when combined with kaempferol,effectively induced cell death in various glioma cells,but not in normal astrocytes.While kaempferol treatment increased the numbers of lysosome,chloroquine treatment increased lysosomal masses.Combined treatment with kaempferol and chloroquine induced the expansion and subsequent rupture of lysosomes,leading to the spillage of the lysosomal contents into the cytosol.We found that while kaemfperol treatment increased the active mature forms of cathepsin D,chloroquine treatment completely blocked the processing of cathepsin D.The processing of cathepsin D was also blocked by the combined treatment,but the activity of cathepsin D,which was released from the lysosomes,was restored.The cell death induced by kaempferol and chloroquine in U251 MG cells was accompanied by mitochondrial dysfunction,ER stress,and DNA damage.CONCLUSION Disruption of lysosomal membrane integrity and a resultant release of lysosomal proteases may critically contribute to the irreparable damage of various organelles and glioma cell death by chloroquine plus kaempferol.

Polarographic Studies on Associations of Midecamycin and Chloroquine with Hydrogen Peroxide

The associations of each of midecamycin and chloroquine phosphate to hydrogen peroxide were studied by using linear-potential scan polarography. In a 0.15 mol/L KH 2PO 4-NaOH(pH 7.4) buffer, the association ratio of the association complex of midecamycin to hydrogen peroxide is 1∶1, and the apparent association constant is 7.18. While in a 0.04 mol/L NH 3·H 2O-NH 4Cl(pH 9.5) buffer, the association ratio and the apparent association constant of the association complex of chloroquine phosphate to hydrogen peroxide are 1∶1 and 45.4, respectively. The formation of the association complexes stabilizes H 2O 2 and results in the accumulation of H 2O 2, which is baneful to human body.

In vivo combination therapy of chloroquine and stigmasterol against Plasmodium berghei induced pathologies in mice

Objective:To investigate the effect of combination therapy of chloroquine and stigmasterol on Plasmodium berghei(thereafter referred to as P.berghei)malaria-induced organ pathologies.Methods:Thirty five mice weighing 20-30 g were placed into seven groups of five mice each and distributed as uninfected administered 100 mg/kg BW stigmasterol,uninfected administered only feed and water ad libitum,infected with P.berghei and-administered 50 mg/kg BW stigmasterol,100 mg/kg BW stigmasterol,100 mg/kg BW stigmasterol plus 5 mg/kg BW chloroquine,and 5 mg/kg BW chloroquine.The last group of mice served as P.berghei infected and not treated control.The levels of parasitemia,packed cell volume,and other biochemical parameters were measured.Results:Combination therapy of P.berghei infection with stigmasterol and chloroquine did not significantly(P>0.05)reduce parasitemia level while stigmasterol treatment alone significantly(P<0.05)reduced the parasitemia level.However,the P.berghei induced anemia was decreased significantly(P<0.05)upon treatment with a combination of chloroquine and stigmasterol as well as with stigmasterol alone.Furthermore,the combination of chloroquine and stigmasterol significantly(P<0.05)decreased the activities of serum alanine aminotransferase,aspartate aminotransferase,urea and spleen total proteins levels in P.berghei mice in comparison with the untreated group.Treatment of P.berghei infected mice with stigmasterol alone and in combination with chloroquine significantly(P<0.05)increased the level of serum creatinine while serum and spleen malondialdehyde levels were significantly(P<0.05)decreased.Levels of glutathione in spleen and kidney were insignificantly(P>0.05)altered upon treatment with both doses of stigmasterol as well as the combination therapy.Conclusions:This study concluded that the combination of stigmasterol and chloroquine could combat anemia and some organ pathologies associated with P.berghei infection.

Worldwide research trends on chloroquine:a bibliometric analysis from 2012 to 2021

Background:Chloroquine(CQ)is an antimalarial drug that was first synthesized by Hans Andersag,a German scientist,in 1934.Chloroquine has been widely researched and used over the years.The rapid development in the fields of modern science and technology has also contributed to the increase in interest in chloroquine.Hence,it is necessary to comprehensively summarize the research trends to understand the breakthroughs made in the field.Methods:The required data was compiled by analyzing the Web of Science Core Collection(WoSCC)database.The search period for studying global research trends in chloroquine research was set from 2012 to 2021 to ensure a comprehensive analysis over an extended timeframe.Data retrieval was performed on April 4,2022,focusing on articles and reviews published in English.The retrieval words were:(TS=(chloroquine))OR(TS=(aralen)).A total of 1,091 reviews and 7,259 articles were retrieved and analyzed.The data obtained from WoSCC was captured and analyzed using VOS viewer(version 1.6.16)and Citesspace(version 5.8.R5).Results:The number of literature reports on chloroquine published in the past 10 years has shown an annual increase.Among the countries,the United States has contributed the highest number of papers and ranks first in terms of both H-index and citation count.The League of European Research Universities is one of the largest research-focused university networks,and Malaria Journal stands out as a prominent journal publishing articles relevant to the field of study.A paper authored by Gautret and Philippe in 2020 achieved the highest citation score globally.The biosynthesis of chloroquine,mechanisms of drug resistance,and drug combinations are receiving growing attention.Conclusion:The research area of chloroquine has been significantly influenced by the American and China.The progress of chloroquine research is further propelled by fruitful collaborations among various countries.Researchers have extensively studied the anti-malarial effect,drug resistance mechanism,and autophagy of chloroquine for the development of a treatment method for COVID-19 based on chloroquine.Bibliometric analysis can be employed to identify hotspots,new directions,and frontiers in the field of chloroquine research.

Reversal of CQ11, a chloroquine derivative, on multidrug resistance in doxorubicin-resistant breast cancer cell line MCF/DOX

Objective： To investigate the reversal effect of CQ11, a chloroquine derivative, on multidrug resistance （MDR） in doxorubicin （DOX）-resistant human breast carcinoma cell line MCF/DOX. Methods： Cells of a human breast cancer cell line, MCF, and its DOX-resistant variant, MCF/DOX, were cultivated with DOX and/or CQ11. The cytotoxicity of drugs in vitro was assayed by MTT method. The accumulation of DOX in these cells was detected by fluorescence spectrophotometer. Results： MCF/DOX cells were 119 times more resistant to DOX in comparison with M CF cells. After simultaneous treatment with CQ 11 at the concentrations of 1.0, 2.5 and 5.0 μmol/L, the IC50 of DOX for MCF/DOX cells decreased from 3.1 ±0.47 μmot/L to 0.58 ± 0.032, 0.19 ± 0.012 and 0.081 ± 0.015 μmol/L, respectively, thus, increasing the DOX sensitivity by 5.3-fold （P 〈 0.01）, 16- fold （P 〈 0.01） and 38-fold （P 〈 0.01）, respectively. In the accumulation assay of DOX, simultaneous incubation of MCF/DOX cells with CQ11 significantly increased the DOX accumulation in MCF/DOX cells. No such results were found in parental MCF cells. Conclusion： CQ11 had strong MDR reversal effect by enhancing intracellular DOX accumulation in MCF/DOX cells, indicating that CQ11 may be a promising MDR chemosensitivity.

In vivo combination therapy of chloroquine and stigmasterol against Plasmodium berghei induced pathologies in mice

Objective:To investigate the effect of combination therapy of chloroquine and stigmasterol on Plasmodium(P.)berghei malaria-induced organ pathologies.Methods:Totally 35 mice weighing 20-30g were placed into 7 groups of 5 mice each and distributed as uninfected administered 100 mg/kg BW stigmasterol,uninfected administered only feed and water ad libitum,infected with P.berghei and administered 50 mg/Kg BW stigmasterol,100 mg/kg BW stigmasterol,100 mg/kg BW stigmasterol plus 5 mg/kg BW chloroquine,and 5 mg/kg BW chloroquine.The last group of mice served as P.berghei infected and not treated control.The levels of parasitemia,packed cell volume,and other biochemical parameters were measured.Results:Combination therapy of P.berghei infection with stigmasterol and chloroquine did not significantly(P>0.05)reduce parasitemia level while stigmasterol treatment alone significantly(P<0.05)reduced the parasitemia level.However,the P.berghei induced anemia was decreased significantly(P<0.05)upon treatment with a combination of chloroquine and stigmasterol as well as with stigmasterol alone.Furthermore,the combination of chloroquine and stigmasterol significantly(P<0.05)decreased the activities of serum alanine aminotransferase,aspartate aminotransferase,urea and level of spleen total proteins in P.berghei infected mice in comparison with the untreated group.Treatment of P.berghei infected mice with stigmasterol alone and in combination with chloroquine significantly(P<0.05)increased the level of serum creatinine while serum and spleen malondialdehyde levels were significantly(P<0.05)decreased.Levels of glutathione in spleen and kidney were insignificantly(P>0.05)altered upon treatment with both doses of stigmasterol as well as the combination therapy.Conclusions:This study concluded that the combination of stigmasterol and chloroquine could combat anemia and some organ pathologies associated with P.berghei infection.

Effects of Chloroquine and Naphthoquinone on Prothrombin Time and Activated Partial Thromboplastin Time of Swiss Mice

Concerns on the coagulation variables, Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) which are part of coagulation parameters used in assessing haemostatsis in haematology, led to the study of the effects of naphthoquinone and chloroquine on the PT and APTT of mice infected with Plasmodium berghei, and treated with graded concentrations of chloroquine and naphthoquinone. Using brain thromboplastin with calcium and rabbit brain cephalosporin ad kaolin respectively the experiment aimed at demonstrating the effect of chloroquine with purity of 99.79% and naphthoquinone with purity of 97.00%, upon a three-day intraperitoneal administration at concentrations of 0.1 mg/kg, 0.5 mg/kg, 1.0 mg/kg and 2.0 mg/kg. Result showed that the APTT and PT of naphthoquinone at 2.0 mg/kg, were 196.67 seconds, and 67.63 seconds respectively, while the APTT and PT of chloroquine were 3.63 seconds and 1.40 seconds respectively for the same concentration. Also, naphthoquinone showed lower APTT but sustained PT at concentrations below 1.50 mg/kg whereas both APTT and PT increased from concentrations above 1.50 mg/kg. On the other hand chloroquine showed a lowered APTT between 0.00 to 0.15 mg/kg while PT was sustained, but both APTT and PT increased from concentration of 0.15 mg/kg gradually. This study conclusively showed that chloroquine has a shorter APTT and PT than naphthoquinones, even though they elicited similar actions. Apart from this, naphthoquinone and chloroquine belonging to the same family, naphthoquinone could be more toxic than chloroquine at the dosages equivalent to 1.50 mg/kg, therefore, any administration of naphthoquinone above this dosage should be closely monitored to avoid any form of danger to the patient.

The Effect of Chloroquine on Pro-Inflammatory Cytokines Levels in Graves’ Disease: Historical Cohort from a Pilot Randomized Controlled Trial

Objectives: Analyzing the trend in the serum inflammatory cytokines levels in a historical cohort of patients treated with combination of chloroquine and methimazole. Material and methods: We analyzed the pro-inflammatory serum cytokines level [Interleukin-6(IL-6), Tumor Necrosis Factor alpha (TNF-α), Interleukin 1 alpha (IL-1 α) and Interferon gamma (INF-γ)] in the stored blood samples of 22 patients with Graves’ disease who previously randomized to receive either chloroquine and methimazole combination therapy or methimazole monotherapy. Total T3, T4 and TSH levels were measured by an enzyme linked immunosorbent assay (ELISA) method (DRG, New York, USA) and the result was published previously. In this study we used an ELISA method (Bender Medsystem Vienna Austria) to measure serum pro-inflammatory cytokines in the first 6 months of trial. Results: No significant differences in serum cytokines concentration were observed between the two treatment groups (p > 0.05). Although it was not statistically significant, serum INF-gamma concentration tended to be lower in the chloroquine group after four months of therapy (p = 0.12). Conclusion: In this study we found changes in the serum thyroid hormones level did not accompany concomitant changes in the serum cytokines levels in two treatment groups. Therefore it is possible that chloroquine reduce serum thyroid hormones levels independent of its immunomodulatory effect.

Determination of Effect of Home-Based Oral Chloroquine Treatment on Haematological Indices of <i>P. falciparum</i>Malaria in Children under 5 Years in Jos Metropolis

Background: The incidence of P. falciparum malaria is characterized by high rates of morbidity and mortality in under 5 children;a trend reportedly prevalent in tropical and subtropical countries including Nigeria, and recently observed in Jos metropolis, has to date defied all constructive, preventive and drug therapy intervention measures and consequently continues to constitute a serious public health problem in this most vulnerable group. Objective: The aim of this study was to determine certain haematological indicators of malaria parasite infection;their role in the clinical manifestation of P. falciparum malaria and effect of first line oral chloroquine treatment in children under 5 years attending Jos University Teaching hospital and OLA Hospital in Jos metropolis. Method: This is a cross-sectional study of 93 malaria and non-malaria children, age 1 - 59 months attending Jos University Teaching Hospital (JUTH), Jos and OLA hospital, Jos, North Central Nigeria. Malaria diagnosis was carried out using microscopical examination of Leishman’s stained thick and thin blood films and complete blood count was done using Beckman Coulter Analyzer. Results: The mean percentage lymphocyte value of chloroquine treated children (39.28% ± 7.45%) was significantly lower than the control (66.38% ± 2.27%). The mean granulocyte value of chloroquine treated children (51.07% ± 6.40%) was significantly higher than the control (26.69% ± 2.43%). Red Blood Cell (RBC) counts (4.01 ± 0.21 × 106/μL), Haemoglobin concentration (9.60 ± 0.51 g/dl) and Haematocrit (30.97% ± 1.43%) of chloroquine treated children were significantly higher than corresponding values in untreated malarious children, but not significantly different from values obtained in non-malaria control children. The RBC counts (2.92 ± 0.39 × 106/μL), Haemoglobin concentration (7.23 ± 1.01 g/dl) and Haematocrit (23.70% ± 3.37%) obtained for untreated malarious children were significantly lower than corresponding values in the non-malarious control children. Conclusion: The pattern of the results obtained in this study suggests that home-based, first-line oral chloroquine treatment 24 hours prior hospital admission decreases the lymphocytes production and elevated production of granulocytes with attendant consequences on their biological functions. The chloroquine treatment seems to protect the red blood cells against the destructive effect of malaria. The haemoglobin concentration of 7.23 ± 1.01 g/dl obtained in untreated malaria children when combined with results of red blood cells;differential analysis indicates a mild, normocytic, normochromic anaemia due to haemolysis. This study demonstrates the beneficial effects of first aid, home-based oral chloroquine use. Rational use of chloroquine needs to be re-evaluated and encouraged in this group of children.