Article

The effects of quinine therapy on the seminal fluid analysis and histology of testes of male rats

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Abstract

The effects of intra muscular (IM) administration of quinine (Qu) on the seminal fluid analysis and testicular histology was studied. Thirty adult male Sprague-Dawley rats were randomly divided into five experimental groups (6 rats per group). Group 1 (control) were given clean drinking water and rat chow, group 2 were given intra-muscular (IM) quinine injection 10mg/kg body weight + water + rat chow. Group 3 and 4 were given, IM quinine 10mg/kg body weight + water + rat chow and graded proportions of extract of Telfairia occidentalis of 4.5g, and 6.0g, respectively. While Group 5 were given rat chow + water + 6.0g of Telfairia occidentalis. The results show a destruction in the testicular histology, decreased sperm count, activity and morphology of Group 2 administered with quinine only, which was statistically significant (P<0.05), and there was also a dose-dependent improvement in the parameters studied in the Group (3 and 4) given extract of Telfairia occidentalis. Group 5 did not show any Testicular destruction but showed an increase in sperm count, morphology and activity but was not statistically significant (P>0.05). This shows that Qu therapy has a destructive effect on the histology of testes and decreased the sperm count, activity and morphology but these effects could be reversed by the administration of extract of Telfairia occidentalis.

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... Antimalarials are said to be efficient due to their oxidant effect [26]. Antiplasmodial drugs quinine [27], chloroquine [28], pyrimethamine [29], artemisinin-based combination treatments [30], have been well documented. P. amarus, the plant used in our present study, which presented significant antimalarial activity, has also been reported to induce antifertility. ...
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Objective To evaluate the antiplasmodial activity of Phyllanthus (P.) amarus crude ethanol leaf extract and its effects on semen quality in male BALB/c mice. Methods A total of 36 adult mice were divided into six groups, with 6 mice each. Five groups were infected with Plasmodium (P.) berghei , and one group was left uninfeceted. Of the five infected groups, one group was left untreated, three groups were treated with varying doses (100, 250 and 400 mg/kg) of P. amarus crude ethanol leaf extract orally for 4 days, and another group was treated with standard drug, artemether and lumefantrine (Lonart ® DS). Antiplasmodial activity, seminal quality, some biochemical indices (neutral α -glucosidase, fructose, and citric acid) in seminal plasma and seminal antioxidant markers (catalase, glutathione peroxidase, reduced glutathione, malondialdehyde, total antioxidant capacity, and acid phosphates) were determined. The mice were euthanized 3 days post treatment and semen was collected from the caudal epididymis and processed for analysis using documented methods and procedures. Results Malarial infection led to oxidative stress, causing a significant decline in seminal quality ( P <0.05). However, treatment with P. amarus crude ethanol leaf extract alleviated oxidative stress and significantly improved seminal quality. The improvement was dose-dependent and compared well with the standard drug, artemether and lumefantrine (Lonart ® DS) treatment. Conclusions The ethanol leaf extracts of P. amarus al leviate male reproductive capacity during malaria infection in murine model by enhancing antioxidant activities.
... Some studies established that quinine is a testicular toxicant (Osinubi, Ajala, Noronha, Okanlawon, 2006). The toxic effects of this anti-malarial alkaloid on human and animal sperms have been observed by biomedical researchers applied in vivo and in vitro.The inhibitory effect of both quinine and chloroquine on sperm metabolism (measured by production of lactic acid and CO 2 ) and motility have been reported (Trifunac, Bernstein, 1982), moreover in vitro study showed the spermicidal activity of quinine after 20 sec of incubation sperms with this alkaloid resulted about 100% of human spermatozoa were immobilized (Garg, Doncel, Chabra, Upadhyay, Talwar, 1994).Another in vivo study in rats observed the toxic effect of short term administration of quinine on the seminiferous tubules , determined that disturbance of spermatogenesis (Osinubi, Akinlua, Agbaje, Noronha, Okanlawon, 2004) and degenerative histological changes in the germinal epithelium as well as statistically significant decrease in sperm count, sperm activity and percentage normal morphology (Nwangwa, Igweh, Uzuegbu, Adegor, 2007) .This seems to be participate by the report by Abayomi etal.(1992) that chloroquine treatment of rats eventually would lead to infertility by resulting in late germ cell developmental with depletion of spermatids (Abayomi O, 1992).This suggested the requirement for the quinine to occupied a place as a male contraceptive agent in humans (Osinubi et al., 2004). Therefore we concluded from this study that the proposition based on the findings in studies in non-human subjects that short-term use of agent to treat malaria has a significant anti-spermatogenic and anti-fertility or contraception. ...
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The intentional avoidance of conception via the using a various strategy, sexual practices, chemicals, drugs or surgical method. A successful contraception was permitting a physical relationship between partners without worrying about an unwanted pregnancy and makes sure a freedom to have children when in demand. The purpose is to attain contraception with a highest confidentiality and a minimum cost and side effects. Even though, the intention to finding a new approach of male contraceptives through targeting ion channels was disturbed by lacking the most molecular basis of channels to effect on sperm function. Recently, there is developing of a new approach push of male contraception, based on targeting specific processes in sperm development, maturation, and function by using quinidine as a one of calcium channel blocker. Consequently depending on previous findings and researches on sperm-specific Ca 2+ channels, as new non-hormonal drug targets for male contraception. 1. Background of Male Contraception Clear evidence observed that women instead of men are paying interestingly for birth control. From many years ago, in addition no attention has been given to men as women. For this reason in the market, many of the contraceptive methods are female oriented (Nabi et al, 2014). New male methods of contraception have not been available. The sperm channel approach based on inhibition of calcium entry to sperm and, as a result, shows its effected on testicular function and spermatogenesis, which investigated for several decades. This approach achieves enough suppression of spermatogenesis to succeed contraception in most men, but not all; the basis for men to respond to this way still unclear. On the other hand, the establishment of non-hormonal approach depended on sympathize specific processes in sperm development, maturation, and function. A variety of targets in animal models has been well-known. This approach, however, still under in the preclinical trial at present. As a result, fundamentally for considering if it is safe have no harmful effects, should be efficient and reversible with minimum cost, then the new method of male contraception can be developed.
... Most of the in-vivo and in-vitro studies to determine the effect of quinine on the reproductive system and function have been carried out on males. The reports from some of these studies using animal models have shown that quinine possesses anti-spermatogenic activities: disrupts spermatogenesis, reduces sperm motility, morphology and sperm count and is deleterious to testicular histoarchitecture [8][9][10] . There is a dearth of literature on the effect of quinine on the female reproductive system. ...
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Background: Quinine has been reported to possess anti-spermatogenic activities. Objectives: This study was carried out to determine the effect of quinine on ovarian function in Sprague-Dawley rats. Methods: Twenty rats with regular 4-days oestrous cycle divided into 4 groups (N=5) were used. Group I received quinine at 30 mg/kg body weight by gavage for 28 days after which they were sacrificed. The ovaries were excised for biochemical oxidation of glutathione peroxidase (GSH), superoxide dismutase (SOD), catalase and malondialdehyde (MDA). Group II received single dose quinine at 30 mg/kg body weight at 0900 hrs on day of proestrus. Blood was obtained at 1800 hrs for hormonal assay of FSH and LH. The animals were sacrificed the next morning on estrus: oviducts were examined for ova count. Groups III and IV served as controls. Results: Quinine treated rats recorded zero number of ova compared to control. Serum concentration of LH reduced significantly in the quinine treated group compared to the control. Furthermore, quinine significantly decreased the oxidant status of GSH, SOD and catalase and significantly increased MDA levels in the ovary compared to the control group. Conclusion: Quinine completely blocks ovulation, suppresses LH surge, and produces oxidative stress in the ovary.
... Some studies established that quinine is a testicular toxicant (Osinubi, Ajala, Noronha, Okanlawon, 2006). The toxic effects of this anti-malarial alkaloid on human and animal sperms have been observed by biomedical researchers applied in vivo and in vitro.The inhibitory effect of both quinine and chloroquine on sperm metabolism (measured by production of lactic acid and CO 2 ) and motility have been reported (Trifunac, Bernstein, 1982), moreover in vitro study showed the spermicidal activity of quinine after 20 sec of incubation sperms with this alkaloid resulted about 100% of human spermatozoa were immobilized (Garg, Doncel, Chabra, Upadhyay, Talwar, 1994).Another in vivo study in rats observed the toxic effect of short term administration of quinine on the seminiferous tubules , determined that disturbance of spermatogenesis (Osinubi, Akinlua, Agbaje, Noronha, Okanlawon, 2004) and degenerative histological changes in the germinal epithelium as well as statistically significant decrease in sperm count, sperm activity and percentage normal morphology (Nwangwa, Igweh, Uzuegbu, Adegor, 2007) .This seems to be participate by the report by Abayomi etal.(1992) that chloroquine treatment of rats eventually would lead to infertility by resulting in late germ cell developmental with depletion of spermatids (Abayomi O, 1992).This suggested the requirement for the quinine to occupied a place as a male contraceptive agent in humans (Osinubi et al., 2004). Therefore we concluded from this study that the proposition based on the findings in studies in non-human subjects that short-term use of agent to treat malaria has a significant anti-spermatogenic and anti-fertility or contraception. ...
Article
The intentional avoidance of conception via the using a various strategy, sexual practices, chemicals, drugs or surgical method. A successful contraception was permitting a physical relationship between partners without worrying about an unwanted pregnancy and makes sure a freedom to have children when in demand. The purpose is to attain contraception with a highest confidentiality and a minimum cost and side effects. Even though, the intention to finding a new approach of male contraceptives through targeting ion channels was disturbed by lacking the most molecular basis of channels to effect on sperm function. Recently, there is developing of a new approach push of male contraception, based on targeting specific processes in sperm development, maturation, and function by using quinidine as a one of calcium channel blocker. Consequently depending on previous findings and researches on sperm-specific Ca 2+ channels, as new non-hormonal drug targets for male contraception. 1. Background of Male Contraception Clear evidence observed that women instead of men are paying interestingly for birth control. From many years ago, in addition no attention has been given to men as women. For this reason in the market, many of the contraceptive methods are female oriented (Nabi et al, 2014). New male methods of contraception have not been available. The sperm channel approach based on inhibition of calcium entry to sperm and, as a result, shows its effected on testicular function and spermatogenesis, which investigated for several decades. This approach achieves enough suppression of spermatogenesis to succeed contraception in most men, but not all; the basis for men to respond to this way still unclear. On the other hand, the establishment of non-hormonal approach depended on sympathize specific processes in sperm development, maturation, and function. A variety of targets in animal models has been well-known. This approach, however, still under in the preclinical trial at present. As a result, fundamentally for considering if it is safe have no harmful effects, should be efficient and reversible with minimum cost, then the new method of male contraception can be developed.
... For the sperm motility, one epididymis of the rat was minced, a few drops of physiological saline were dropped on the slide, the tissure were moved back and forth a few times until semen is transferred to the slide. Under a microscope using a neubaer hemocytometer at 40x objective lens the active progressive sperm movement, sluggish sperm movement and non-motile were compared by the methods of Linder et al., 1988, Liobet et al., 1991, and Nwangwa et al., 2007. ...
... For the sperm motility, one epididymis of the rat was minced, a few drops of physiological saline were dropped on the slide, the tissure were moved back and forth a few times until semen is transferred to the slide. Under a microscope using a neubaer hemocytometer at 40x objective lens the active progressive sperm movement, sluggish sperm movement and non-motile were compared by the methods of Linder et al., 1988, Liobet et al., 1991, and Nwangwa et al., 2007. ...
... It concluded that quinine had deleterious effects on the seminiferous tubules of Sprague Dawley rats and may possibly disrupt spermatogenesis and suggested the need for the exploration of the place of quinine as a male contraceptive agent in humans (Osinubi et al., 2004). A third in vivo study in Sprague Dawley rats also reported degenerative histological changes in the germinal epithelium as well as statistically significant decrease in sperm count, sperm activity and percentage normal morphology (Nwangwa et al., 2007). Ashiru et al. (1991) also reported that the injection of rats with chloroquine for 16 weeks eliminated all Leydig cells. ...
Article
The effects of treatment with the anti-malarial alkaloids quinine and chloroquine on sperm properties and blood levels of selected reproductive hormones (testosterone, follicle stimulating hormone and luteinizing hormones) of adult men were determined. Informed consents were obtained from twenty healthy adult volunteers who were subsequently allotted to groups A and B with 5 subjects each .While group C had 10 subjects. Group A received 600 mg of quinine 8 hourly for 5 days; group B subjects had 4 tablets of chloroquine (250 mg each) daily for 2 days then 2 tablets for one day. Group C subjects had neither of these drugs in the study period of 65 days. Venous blood and masturbation specimens of semen were obtained from the subjects before treatment, immediately post-treatment and by the 65 th day from commencement of treatment. Blood levels of follicle stimulating hormones, leutinizing hormone and testosterone were determined by Enzyme Linked Imuno Assay. Seminal Fluid Analysis was carried out on the semen specimens to determine sperm count, percentage forward motility and percentage abnormal sperm morphology. The means of all the variables assessed were within the limits of normal for their respective method of analysis. No statistical significant effect of these drugs on sperm count, percentage sperm forward motility and blood levels of testosterone were observed when pre-treatment results were compared with post-treatment and 65 th day results as well as when results of quinine and chloroquine treated groups were compared with those of control group. The suggestion by disparate in vivo animal and in vitro studies that the short term use of these drugs to treat malaria may be associated with fertility changes as a result of their inherent anti-spermatogenic effects have not been collaborated by this study in adult men.
... A third in vivo study in Sprague Dawley rats also reported degenerative histological changes in the germinal epithelium as well as statistically significant decrease in sperm count, sperm activity and percentage normal morphology (Nwangwa et al., 2007). Ashiru et al. (1991) also reported that the injection of rats with chloroquine for 16 weeks eliminated all Leydig cells. ...
Article
The effects of treatment with the anti-malarial alkaloids quinine and chloroquine on sperm properties and blood levels of selected reproductive hormones (testosterone, follicle stimulating hormone and luteinizing hormones) of adult men were determined. Informed consents were obtained from twenty healthy adult volunteers who were subsequently allotted to groups A and B with 5 subjects each .While group C had 10 subjects. Group A received 600 mg of quinine 8 hourly for 5 days; group B subjects had 4 tablets of chloroquine (250 mg each) daily for 2 days then 2 tablets for one day. Group C subjects had neither of these drugs in the study period of 65 days. Venous blood and masturbation specimens of semen were obtained from the subjects before treatment, immediately post-treatment and by the 65 th day from commencement of treatment. Blood levels of follicle stimulating hormones, leutinizing hormone and testosterone were determined by Enzyme Linked Imuno Assay. Seminal Fluid Analysis was carried out on the semen specimens to determine sperm count, percentage forward motility and percentage abnormal sperm morphology. The means of all the variables assessed were within the limits of normal for their respective method of analysis. No statistical significant effect of these drugs on sperm count, percentage sperm forward motility and blood levels of testosterone were observed when pre-treatment results were compared with post-treatment and 65 th day results as well as when results of quinine and chloroquine treated groups were compared with those of control group. The suggestion by disparate in vivo animal and in vitro studies that the short term use of these drugs to treat malaria may be associated with fertility changes as a result of their inherent anti-spermatogenic effects have not been collaborated by this study in adult men.
Thesis
Chloroquine and hydroxychloroquine belong to the quinolone family. They are related drugs with different therapeutic and toxic doses with similar clinical indications for use. Initially, chloroquine was given for malaria prophylaxis and treatment, and later it is used by rheumatologists for treating rheumatoid arthritis, systemic/discoid lupus erythematosus, and other connective tissue disorders. Hydroxychloroquine has replaced chloroquine since it is far less toxic, except for individuals who travel in areas endemic with malaria Expanded use of these drugs for nonmalarial disease entities has resulted in prolonged duration of therapy and higher daily dosages leading to cumulative doses greater than those used in antimalarial therapy Prevalence rate of autoimmune disesases in Egypt is 0.2 cases per 100 inhibitants. Chloroquine toxicity is thought to be due to the formation of some oxidative metabolites, which raises the production of reactive oxygen species Possible mechanisms of testicular toxicity of chloroquine are interference with several enzymatic activities like glucose 6-phosphate dehydrogenase activity, alteration in phospholipids compositions of microsoms, mitochondrial NADH, succinate dehydrogenase and cytochrome C oxidase Many histolpathological changes in testis were detected in chloroquine phosphate poisoning e.g shrunken Seminiferous tubules, degeneration of the interstitial tissues, loss of interstitial cells of leydig , degeneration of sertoli cells and degeneration of spermatocytes and spermatids, Chloroquine can cause reductions in sperm motility and viability, increase in the number of abnormal spermatozoa and reduction in the weight of the testes Hydroxychloroquine is found to be less toxic than chloroquine, while there are no reports of adverse effects of hydroxychloroquine on male fertility
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Recently, there is developing of a new approach push of male contraception, based on targeting specific processes in sperm development, maturation, and function by using quinidine as a one of calcium channel blocker.The effect of antimalarial alkaloids Quinidine (QD) investigated in the testicular tissue, Ca 2+ level and some sperm parameters in male mice. To evaluate the impact of QD as a Ca 2+ channel blocker on Ca 2+ level, the sperms are exposed to QD directly at concentration 10 and 50 µm through perfusion apparatus have a multiple connecting tubes which perfuse QD directly to the imaging chamber containing sperms, then the Ca 2+ imaging have done by using laser scanning fluorescence microscope. While the effects of QD on the sperm parameters (motility, abnormality and death percentages) observed by incubation sperms in chambers containing QD at 500 µm for 2 hours. The result showed a significant decrease (p<0.05) in sperm motility, with an increase in abnormality and death percentages with reversible recovery after Hanks Solution (HS) wash at pH 7.4.On the other hand the sperms were incubated in QD at concentrations 10, 50 µm from 2 to 14 hours respectively, have no any changes on in these sperm parameters and testicular tissues at these lower concentration of QD. Although the effects were apparent on sperm parameters after incubation with QD at 500 µm for 2 hours. Histology disturbance was significantly increased after incubation of testis tissue for 14 hours with QD at Concentration 500µm as compared to control. The changes caused by QD only recovered on sperm parameters and Ca 2+ level after washing the sperm with Hanks solution medium (HS) medium containing 2mM Ca 2+ at pH 7.4. So under the exposure to QD, the inhibitory effect on fertility parameters of mouse's sperms are reversible due to Hanks (HS) supplementation, but there is no recovery determined in testicular tissues treated by QD even when it washed by HS supplementation.
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Full-text available
Recently, there is developing of a new approach push of male contraception, based on targeting specific processes in sperm development, maturation, and function by using quinidine as a one of calcium channel blocker.The effect of antimalarial alkaloids Quinidine (QD) investigated in the testicular tissue, Ca 2+ level and some sperm parameters in male mice. To evaluate the impact of QD as a Ca 2+ channel blocker on Ca 2+ level, the sperms are exposed to QD directly at concentration 10 and 50 µm through perfusion apparatus have a multiple connecting tubes which perfuse QD directly to the imaging chamber containing sperms, then the Ca 2+ imaging have done by using laser scanning fluorescence microscope. While the effects of QD on the sperm parameters (motility, abnormality and death percentages) observed by incubation sperms in chambers containing QD at 500 µm for 2 hours. The result showed a significant decrease (p<0.05) in sperm motility, with an increase in abnormality and death percentages with reversible recovery after Hanks Solution (HS) wash at pH 7.4.On the other hand the sperms were incubated in QD at concentrations 10, 50 µm from 2 to 14 hours respectively, have no any changes on in these sperm parameters and testicular tissues at these lower concentration of QD. Although the effects were apparent on sperm parameters after incubation with QD at 500 µm for 2 hours. Histology disturbance was significantly increased after incubation of testis tissue for 14 hours with QD at Concentration 500µm as compared to control. The changes caused by QD only recovered on sperm parameters and Ca 2+ level after washing the sperm with Hanks solution medium (HS) medium containing 2mM Ca 2+ at pH 7.4. So under the exposure to QD, the inhibitory effect on fertility parameters of mouse's sperms are reversible due to Hanks (HS) supplementation, but there is no recovery determined in testicular tissues treated by QD even when it washed by HS supplementation.
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Quinine (QU) has been used worldwide in the suppression and treatment of malaria for more than 350 years. The aim of this study was to determine the long-term morphological response of the testis to long-term administration of QU using stereological parameters. 64 adult male Sprague-Dawley rats weighing 180-200g were used. The animals were randomly divided into 8 groups of 8 rats each. Every experimental animal had intramuscular QU at a dose of 10mg/kg body weight per day (5 times in a week, with the exception of group 1 animals). Group 1 rats had QU for 1 week (7 days consecutively) and were sacrificed on the last day of injection. Groups 2 and 3 rats had QU for 4 and 6 weeks and were sacrificed at the end of the 4th and 6th week respectively. Group 4, 5, 6 and 7 rats had QU for 8 weeks and were sacrificed at the end of week 8, 12, 16 and 20 respectively. Group 8 animals constituted the controls and had equal volume of distilled water intramuscularly for 8 weeks. All sacrifices were by decapitation. The testes were carefully dissected out, their volumes measured, weighed and histological sections prepared. Morphometric assessment was carried out using the diameter, cross-sectional area, number of profiles per unit area, numerical density and volume density of the seminiferous tubules and the relative and absolute volume of the seminiferous epithelium, stroma and lumen of tubules. The results showed that there was a general destruction of cells of the seminiferous tubules and the testicular interstitium that persisted even after the discontinuation of QU and to the end of our experiment that lasted 20 weeks. We conclude that QU has deleterious effect on the seminiferous tubules of Sprague-Dawley rats, though the mechanism of damage is unclear.