ABSTRACT
Objective To investigate the effects of nitroquine on the development of different stages of Plasmodium yoelii in Anopheles stephensi. Methods An. stephensi mosquitoes were fed with conventional sucrose water or sucrose water containing 100 μmol/L nitroquine one day prior to P. yoelii infection. Following starvation for 24 hours, mosquitoes were fed with the blood of Kunming mice infected with P. yoelii, and the number of oocysts was observed in the stomach of An. stephensi. After 6 days and 14 days of infection, the mosquitoes were starved for 24 hours, and then fed with conventional sucrose water or nitroquine treated sucrose water. The An. stephensi mosquitoes were starved for 24 hours 6 and 14 days post-infection with P. yoelii, and then fed with conventional sucrose water or nitroquine-containing sucrose water, the numbers of P. yoelii sporozoites were examined in the hemolymph and salivary glands of An. stephensi. Results Following exposure to nitroquine-containing sucrose water one day prior to P. yoelii infections, the number of P. yoelii oocysts was significantly lower in the An. stephensi stomach on day 7 (119.2 ± 16.1 vs. 207.3 ± 21.8; t = 3.207, P < 0.05). After conventional sucrose water was ceased for 24 hours on day 6, and An. stephensi was fed with nitroquine-containing sucrose water, the number of P. yoelii sporozoites peaked in the hemolymph on day 14 in the nitroquine treatment group (952.3 ± 22.7) and on day 12 in the sucrose water treatment group (1 287.0 ± 39.0), and there was a significant difference in the number of sporozoites in the salivary glands between the nitroquine treatment group and the sucrose water treatment group (9 467.0 ± 1 304.0 vs. 10 533.0 ± 758.7; t = 0.707, P = 0.506) on day 17. After conventional sucrose water was ceased for 24 hours on day 14, and An. stephensi was fed with nitroquine-containing sucrose water, the number of sporozoites in the salivary glands was significantly greater in the nitroquine treatment group than in the sucrose water treatment group (21 900.0 ± 2 613.0 vs. 10 533.0 ± 732.3; t = 4.188, P < 0.05). Conclusions Nitroquine treatment exhibits diverse effects the development of different stages of P. yoelii, and nitroquine treatment may reduce the transmission of P. yoelii in uninfected An. stephensi.
ABSTRACT
After a single oral dosed mg/kg) of nitroquine to the mice infected with Plasmodium yoelii,the morphological changes of the parasites were studied with optical and electron microscopy.Enlarged nucleus and some red granules scattered over the cytoplasm in the late trophozoites were observed under optical microscope,which may correspond to the autophagocytic vacuo-les or membranous residual bodies seen under electron microscope.Thirty minutes after the drug administration,the number of mitochondria with matrix cavitation was increased,the endoplasmic reticulum dilated,and ribosomes separated,detached,or disaggregated.Then the pelliculous complex and nuclear membrane of the parasites proliferated to form multi-layered structure with spiral curv?s or myelin sheath-like structure in the cytoplasm.The nuclear membrane was swollen and proliferated and the perinuclear cisterna was widened.In the late stage of drug action,the structure of the parasites was broken down to form a large number of autophagocytes.The findings indicate that nitroquine interferes with the structure and function of the cell membrane,cytoplasm and nucleus of malaria parasites and exerts its anti-malarial effects from many aspects.
ABSTRACT
Objective To analyze the relationship between the TEP1 gene of Anopheles stephensi and melanotic encapsulation of Plasmodium yoelii induced by anti-malaria drug nitroquine. Methods Haemolymph samples from three groups of An. stephensi fed with sucrose solution, Plasmodium-infected blood and nitroquine, respectively, were collected at the 1st, 2nd, 3rd and 4th day after drug adminstration. Degenerate primers were designed according to the conserved amino acid sequence within TEPs of the mosquitoes. Fluorescent quantitation PCR was used to detect the variation of TEP1 gene transcript induced by nitroquine. The melanization of oocysts was observed by light microcopy. Results TEP1 gene was cloned, the predicted amino acid residues harbored a highly conserved canonical thioester motif GCGEQ. The fluorescent quantitation PCR revealed that nitroquine induced an up-regulation of TEP1 activity. The transcription of TEP1 gene in nitroquine treated group (2.423) was significantly higher than that of the infected blood-fed group(1.036) at the 3rd day after nitroquine treatment (P
ABSTRACT
The effects of nitroquine on the sporogonic development of Plasmo-dium yoelii were observed under electron microscopy. The female mosquitoes were fed directly with 10% sucrose solution containing 0.1%Nitroquine.It was found that the oocysts were smaller and markedly degenerated as compared with that of the control. The surface of the oocysts was rough and uneven. Under a transmission electron microscope, the cytoplasm of the affected oocysts contained vacuoles; the membane of mitochondria and uncleus was damaged; and the number of residual bodies increased.No sporoblast formation was seen in most of the affectes oocysts. The nuclear membrane of the degenerated sporozoites was thickened and the density of nuclear matrix decreased markedly as compared with that of the control. These results indicate that the nucleus and the membrane are mainly affected during the sporogonic development of P. yoelii by nitroquine.
ABSTRACT
Wistar rats -were given orally a single dose of nitroquine acetate ( 1 mg/kg) 24 hours after an intravenous inoculation of the sporoizoites of Plasmodium yoelii yoelii strain BY 265. Liver biopsies were taken and some animals were killed at regular intervals to observe the exoerythrocytic forms(EEF). Blood smears of some animals were made to observe the parasitemia. The results were , as follows.1. The density of the EEF in the livers of the treated animals was low but the number of degenerated EEF was high 48 hours after inoculation. At this time, the EEF was smaller in size with less number of nucleus, but with irregular nuclear masses. The EEF at 54, 65 and 72 hours were characterized by un- even size of the nuclei, which were disproportionate to the size of the parasites, and by much more irregular masses of nucleus. Some degenerated EEF infiltrated by WBC could be found. There was no matured tissue schizont within 72 hours after sporozoile inoculation.2. Only 1 out of the 8 treated animals became patent of parasitemia of low level with a prolonged prepatent period.The results indicate that nitroquine exerts a causal prophylactic effect on rodent malaria and interferes with the development of EEF by suppressing the ouclear division
ABSTRACT
The toxic effects of nitroquine-dapson compound(NQD) per os in mice and dogs were studied. The therapeutic index of NQD in mice(1911) is the highest among the six antimalarial preparations studied. The toxic effects(50mg/kg/ day for 3 successive days per os) in dogs were similar to those of nitroquine. They manifested themselves as the injury on the adrenal cortex and on the intestinal epithelium. When folic acid (4 mg/kg/day for 4 successive days) or folinic acid(0.3 mg/kg/day for 4 successive days) was administered intramuscularly to the toxicated animals, both the death rate and the incidence of diarrhea were greatly reduced. Pathological study confirmed that the injury on the intestinal epithelium was much milder and the goblet cell was much more numerous in the treated than in the untreated. The results suggest that folic acid or folinic acid can protect the less differentiated cells in the intestinal crypts, so that the clinical manifestations of NQD toxicity are reduced after treatment.
ABSTRACT
Objective To analyze the protein in hemolymph from adult female Anopheles stephensi (An. Stepheni) infected by Plasmodium yoelii after feeding with sucrose solution containing nitroquine or simple sucrose solution with two dimensional gel electrophoresis technique. Methods Hemolymphs from nitroquine fed, infected blood fed, and sucrose solution fed adult female An. stephensi were collected using the expulsion method on the third day after the feeding. Hemolymph protein concentration was examined with Bradford method. Then the hemolymph protein was analyzed by two dimensional electrophoresis. The protein spots were visualized by Coomassie brilliant blue staining. The spots were scanned and automatically analyzed by the ImageMaster VDS CL (Amersham Pharmacia) and ImageMaster 2D Elite software (Amersham Pharmacia). Results The protein concentration in the nitroquine fed group was always lower than that in the infected blood fed and sucrose solution fed groups. Two dimensional gel electrophoresis revealed 101 protein spots in nitroquine fed and 115 protein spots in the control with 51 matched, but unmatched 50 and 64 protein spots were detected in the treatment group and the control group, respectively. Different protein spots were mainly located at the molecular weight of (40-60)?10 3 and at the isoelectric points of basic end. Conclusion Two dimensional gel electrophoresis may directly reflect the difference of the protein. Both the difference of protein concentration and the protein spots may be involved in nitroquine induced melanotic encapsulation of Plasmodium yoelii oocysts.
ABSTRACT
This is a comprehensive review of the work done on the clinical and field application by a team of a new antimalarial nitroquine.A total of 198 acute cases of plasmodium falciparum infection (both chloroquine sensitive and chloroquine-resistant) were treated with nirtoquine-composite 50-70 mg?3d with satisfactory results.The effect of treating 510 acute cases of P.vivax with nitroquine-composite 50 mg?3d was slightly less as compared with routine chloroquine treatment.The prophylactic trials made in 2 chloroquine resistant p.falciparum endemic areas among a total population of 4540 showed that when uitroquine-composite was given in dose of 50 mg/d/15d or 75mg/2d/m gives satisfactory prophylactic effects.Ladoratoty experiments show that nitroquine is effective to the tissue,erythrocytic and sporogonic stages of malaria parasites.A resouable scheme of medicating nitroquine is proposed.