scholarly journals Naphthoquinone impairs reproductive functions in plasmodium berghei berghei-infected male swiss mice

2019 ◽  
Vol 8 (1) ◽  
pp. 1
Author(s):  
Nkereuwem Sunday Etukudoh ◽  
Opeyemi Oreofe Akindele ◽  
Olufadekemi Tolulope Kunle-Alabi ◽  
Adeyombo Folashade Bolarinwa

Background: Various antimalarial drugs adversely affect male reproductive functions. Naphtoquinones, a class of antimalarial drugs have been shown to effectively combat malaria parasites. However, the effects of naphtoquinone on reproductive functions remain elusive. The study determined the effects of naphthoquinone on reproductive functions of Plasmodium berghei berghei-infected male Swiss miceMethods: Thirty male Swiss mice were divided into 6 groups (n = 5) namely; Control, 1 mg/kg naphthoquinone, 2 mg/kg naphthoquinone, Plasmodium berghei berghei (Pbb)-infected, Pbb-infected+1 mg/kg naphthoquinone and Pbb-infected+2 mg/kg naphthoquinone. Parasitaemia was confirmed by microscopy. Naphthoquinone (i.p.) was administered for seven days following confirmation of parasitaemia. Thereafter, they were sacrificed. Serum levels of FSH, LH, testosterone and cortisol were assayed via ELISA. Sperm characteristics were evaluated by microscopy. Data were expressed as mean ± SEM and analysed using ANOVA at p<0.05.Results: Sperm motility reduced in the Pbb-infected compared with control. Sperm viability, motility and count reduced in naphthoquinone only groups and Pbb-infected+naphthoquinone groups compared with the control. Naphthoquinone groups and Pbb-infected alone decreased in LH and testosterone concentrations compared with the control.Conclusion: Naphthoquinone treatment impaired reproductive functions in Plasmodium berghei berghei-infected male Swiss mice.  

2015 ◽  
Vol 43 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Hiroyuki Matsuoka ◽  
Hiroyuki Tomita ◽  
Ryuta Hattori ◽  
Meiji Arai ◽  
Makoto Hirai

2015 ◽  
Vol 36 (6) ◽  
pp. 3699
Author(s):  
Rodrigo Arruda de Oliveira ◽  
Marco Antônio De Oliveira Viu ◽  
Maria Lúcia Gambarini

Handling equine semen during the refrigeration process reduces sperm viability, and consequently causes membrane lipid peroxidation, among other challenges. The present study aimed to evaluate the in vitro effects of glutathione (control, 1. 0, 1. 5, and 2. 5 mM) on equine semen in a refrigeration protocol of 16ºC for 36 hours. The following variables were evaluated after 0, 12, 24, and 36 hours refrigeration: total sperm motility, vigor, viability, and plasma and acrosomal membrane integrity. Motility was higher with 2. 5mM of glutathione (57. 8 ± 7. 3) after 12 hours of refrigeration compared to the control (53. 2 ± 8. 3) (P < 0. 05). After 36 hours of refrigeration, motility was higher with 1. 5 mM (43. 4 ± 12. 7) and 2. 5mM glutathione (45. 5 ± 6. 2), than it was with 1mM glutathione (38. 2 ± 9) and the control (35. 5 ± 18. 4) (P < 0. 05), respectively. Vigor was highest with 1. 5mM glutathione (3. 7 ± 0. 3) after 36 hours compared to the control (3. 2 ± 1. 1), (P < 0. 05). Viability differed between control and 1mM treatments (79. 5 ± 1. 8) only after 24 hours (75. 5 ± 9. 7) (P < 0. 05). Throughout the investigation, no significant differences were noted in plasma and acrosomal membrane integrity (P > 0. 05). The 1. 5 and 2. 5mM glutathione levels were more efficient in protecting sperm cells and yielded higher total motility values after 36 hours of refrigeration.


Author(s):  
I. S. Esua ◽  
U. U. Uno ◽  
U. B. Ekaluo

Background and Aim: Tramadol is a potent analgesic effective in the treatment of mild to severe pains. However, the use of the drug can pose a threat to other organs and systems. Therefore, this study evaluated the effect of graded doses of tramadol on sperm profile of male albino rats. Materials and Methods: Eighteen male rats were divided into three groups (A, B and C) using completely randomized design (CRD) with six rats in each group. Rats in group A served as the control group and were given just food and water while groups B and C were given tramadol at 50 and 100 mg/kg body weight (BW) respectively, daily for the period of 65 days. The treatment was administered via oral gavage and at the end of the treatments, the rats were sacrificed. Immediately after sacrifice, a puncture was made in the epididymis with a sterile pin and examined for semen pH. The epididymes were processed for epididymal sperm motility, viability, count and sperm head abnormality. Results: There was no significant difference in the weight of testes and semen pH. Sperm viability, sperm motility, sperm count and weight of epididymes significantly reduced (p<0.05) in tramadol treated animals when compared with the control. Results also indicated statistically significant (p<0.05) increase in sperm head abnormalities in rats treated with tramadol when compared with the control. Conclusion: The results obtained from this study reveal that tramadol has negative effects on weight of epididymes, sperm count, sperm viability, sperm motility and sperm head abnormalities in male albino rat as mammalian models in a dose dependent manner.


2020 ◽  
Author(s):  
Nelson V. Simwela ◽  
Katie R. Hughes ◽  
Michael T. Rennie ◽  
Michael P. Barrett ◽  
Andrew P. Waters

AbstractCurrent malaria control efforts rely significantly on artemisinin combinational therapies which have played massive roles in alleviating the global burden of the disease. Emergence of resistance to artemisinins is therefore, not just alarming but requires immediate intervention points such as development of new antimalarial drugs or improvement of the current drugs through adjuvant or combination therapies. Artemisinin resistance is primarily conferred by Kelch13 propeller mutations which are phenotypically characterised by generalised growth quiescence, altered haemoglobin trafficking and downstream enhanced activity of the parasite stress pathways through the ubiquitin proteasome system (UPS). Previous work on artemisinin resistance selection in a rodent model of malaria, which we and others have recently validated using reverse genetics, has also shown that mutations in deubiquitinating enzymes, DUBs (upstream UPS component) modulates susceptibility of malaria parasites to both artemisinin and chloroquine. The UPS or upstream protein trafficking pathways have, therefore, been proposed to be not just potential drug targets, but also possible intervention points to overcome artemisinin resistance. Here we report the activity of small molecule inhibitors targeting mammalian DUBs in malaria parasites. We show that generic DUB inhibitors can block intraerythrocytic development of malaria parasites in vitro and possess antiparasitic activity in vivo and can be used in combination with additive effect. We also show that inhibition of these upstream components of the UPS can potentiate the activity of artemisinin in vitro as well as in vivo to the extent that ART resistance can be overcome. Combinations of DUB inhibitors anticipated to target different DUB activities and downstream 20s proteasome inhibitors are even more effective at improving the potency of artemisinins than either inhibitors alone providing proof that targeting multiple UPS activities simultaneously could be an attractive approach to overcoming artemisinin resistance. These data further validate the parasite UPS as a target to both enhance artemisinin action and potentially overcome resistance. Lastly, we confirm that DUB inhibitors can be developed into in vivo antimalarial drugs with promise for activity against all of human malaria and could thus further exploit their current pursuit as anticancer agents in rapid drug repurposing programs.Graphical abstract


2018 ◽  
Vol 7 (4) ◽  
pp. 376-383
Author(s):  
Bankole Olukayode Olusola ◽  
◽  
Oderinde Abdulganiyu Olumuyiwa ◽  

Malaria, a hazardous infirmity caused by a parasitic malady of the red blood cells, is without question harming to the wellbeing. In the present investigation, the chemosuppresive and haematopoietic activities of 200 mg/kg and 400 mg/kg body weight of unrefined ethanolic concentrates of three Chinese green teas (BIA 849, TD 570 and GB/T19598) were assessed using the 4-day suppressive anti-plasmodial assay in mice Plasmodium berghei (NK65 strain) pre-infected mice. The effect of the extracts on weight of the animals was evaluated. It was observed that 200 mg/kg bw (body weight) of BIA 849 and GB/T19598 were as potent as 5 mg/kg bw of chloroquine, with percentage suppressions of 58.97 ± 5.04, 57.63 ± 5.62 and 57.50 ± 4.5, respectively. TD570 at 200 mg/kg bw was more effective in suppressing plasmodium. 400 mg/kg body weight of TD570 and GB/T19598 extracts were more potent than 5 mg/kg bw of chloroquine having 100 % chemosuppression. The chemosuppression of BIA 849 did not change altogether at 400 mg/kg bw. The haematological parameters, WBC, RBC and MCV did not significantly change in the groups treated with the tea extracts utilizing suppressive model of malaria treatment contrasted with the uninfected group and were comparable to those treated with chloroquine. Haemoglobin concentration nonetheless, varied significantly with respect to the uninfected group. Weight changes were most significant with 200 mg/kg bw of TD 570 treated group (32 % increase) on suppression. All in all, the green teas displayed high chemosuppressive and haematopoietic possibilities and are thusly prescribed as contender for additionally screening as elective antimalarial drugs


2021 ◽  
Vol 88 (1) ◽  
Author(s):  
Aboyeji L. Oyewole ◽  
Oluwole Akinola ◽  
Bamidele V. Owoyele

Various types of pain were reported by people with Plasmodium falciparum and were mostly attributed to a symptom of malarial infection. Neural processes of pain sensation during malarial infection and their contributions to malaria-related death are poorly understood. Thus, these form the focus of this study. Swiss mice used for this study were randomly divided into two groups. Animals in the first group (Pb-infected group) were inoculated with Plasmodium berghei to induce malaria whilst the other group (intact group) was not infected. Formalin test was used to assess pain sensitivity in both groups and using various antagonists, the possible mechanism for deviation in pain sensitivity was probed. Also, plasma and brain samples collected from animals in both groups were subjected to biochemical and/or histological studies. The results showed that Pb-infected mice exhibited diminished pain-related behaviours to noxious chemical. The observed parasite-induced analgesia appeared to be synergistically mediated via µ-opioid, α2 and 5HT2A receptors. When varied drugs capable of decreasing pain threshold (pro-nociceptive drugs) were used, the survival rate was not significantly different in the Pb-infected mice. This showed little or no contribution of the pain processing system to malaria-related death. Also, using an anti-CD68 antibody, there was no immunopositive cell in the brain to attribute the observed effects to cerebral malaria. Although in the haematoxylin and eosin-stained tissues, there were mild morphological changes in the motor and anterior cingulate cortices. In conclusion, the pain symptom was remarkably decreased in the animal model for malaria, and thus, the model may not be appropriate for investigating malaria-linked pain as reported in humans. This is the first report showing that at a critical point, the malaria parasite caused pain-relieving effects in Swiss mice.


2013 ◽  
Vol 25 (8) ◽  
pp. 1185 ◽  
Author(s):  
M. Alvarez-Rodríguez ◽  
M. Alvarez ◽  
L. Anel-López ◽  
C. Martínez-Rodríguez ◽  
F. Martínez-Pastor ◽  
...  

Egg yolk low-density lipoproteins (LDL) and soybean lecithin were evaluated as replacements for egg yolk in extenders used for the cryopreservation of brown-bear spermatozoa. The motility, viability and acrosomal status of post-thawed spermatozoa were analysed, and an egg-yolk extender was used as a control. The total antioxidant capacity of these extenders was tested. Soybean lecithin showed an effect that was dependent on the soybean concentration (2%, 3.5% and 5%) and source (Type A: 24% l-α-phosphatidylcholine, and Type B: 14–23% l-α-phosphatidylcholine). Only semen cryopreserved with 5% Type A soybean exhibited a sperm motility similar to that of semen cryopreserved in egg-yolk-based extender after thawing, although the sperm viability and acrosome status were not as high. Semen frozen in an extender containing LDL (10–15%) exhibited improved sperm viability in comparison with the control, but sperm motility was lower. The LDL-based extender exhibited a higher anti-oxidant activity than the egg-yolk extender and soy lecithin-based extenders. The extenders with higher anti-oxidant activity showed improvements in frozen sperm viability but lower semen motility. These results indicate that soybean lecithin did not have the same protective effect as egg yolk during the freezing of brown-bear spermatozoa but suggest that LDL (10–15%) could be a useful substitute for egg yolk in these extenders.


2013 ◽  
Vol 57 (7) ◽  
pp. 3131-3136 ◽  
Author(s):  
Michael P. Draper ◽  
Beena Bhatia ◽  
Haregewein Assefa ◽  
Laura Honeyman ◽  
Lynne K. Garrity-Ryan ◽  
...  

ABSTRACTWith increasing resistance to existing antimalarials, there is an urgent need to discover new drugs at affordable prices for countries in which malaria is endemic. One approach to the development of new antimalarial drugs is to improve upon existing antimalarial agents, such as the tetracyclines. Tetracyclines exhibit potent, albeit relatively slow, action against malaria parasites, and doxycycline is used for both treatment (with other agents) and prevention of malaria. We synthesized 18 novel 7-position modified tetracycline derivatives and screened them for activity against cultured malaria parasites. Compounds with potentin vitroactivity and other favorable drug properties were further tested in a rodent malaria model. Ten compounds inhibited the development of culturedPlasmodium falciparumwith a 50% inhibitory concentration (IC50) after 96 h of incubation of <30 nM, demonstrating activity markedly superior to that of doxycycline (IC50at 96 h of 320 nM). Most compounds showed little mammalian cell cytotoxicity and no evidence ofin vitrophototoxicity. In a murinePlasmodium bergheimodel, 13 compounds demonstrated improved activity relative to that of doxycycline. In summary, 7-position modified tetracyclines offer improved activity against malaria parasites compared to doxycycline. Optimized compounds may allow lower doses for treatment and chemoprophylaxis. If safety margins are adequate, dosing in children, the group at greatest risk for malaria in countries in which it is endemic, may be feasible.


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