ABSTRACT
A cotonicultura tem forte fator de impacto na economia nacional, e o estado de Mato Grosso se destaca por ser o maior produtor de algodão herbáceo e deter o maior rebanho bovino do país, condições essas que estimulam o uso do caroço, da torta e do farelo de algodão na alimentação animal. Considerando que o gossipol está presente nos subprodutos do algodão e que seus efeitos sobre a reprodução podem reduzir a fertilidade dos animais, objetivou-se, com essa pesquisa, avaliar o efeito da ingestão de dietas com diferentes teores de gossipol livre por dia sobre a morfometria testicular e a qualidade seminal de touros da raça Nelore. Foram utilizados 28 touros, distribuídos aleatoriamente em seis tratamentos: T0, 0 grama de gossipol livre/touro/dia ; T1, 1,08 grama de gossipol livre/touro/dia; T2, 2,07 gramas de gossipol livre/touro/dia; T3, 3,24 gramas de gossipol livre/touro/dia; T4, 3,82 gramas de gossipol livre/touro/dia e T5, 5,08 gramas de gossipol livre/touro/dia. Os animais de cada tratamento foram mantidos confinados em área média de 100m2, dotada de bebedouro, cochos para mistura mineral e para volumoso/concentrado. O consumo de 3,24 gramas de gossipol livre/touro/dia alterou a qualidade espermática e a morfometria testicular de touros.(AU)
The cotton industry has a strong impact factor in the Brazilian economy and the state of Mato Grosso stands out for being the largest upland-type cotton producer and also holds the largest cattle herd in the country, conditions that stimulate the use of cottonseed pie and cottonseed meal in animal feed. Whereas gossypol is present in cotton by-products and their effects on reproduction can reduce the animal fertility, this research evaluated the effect of diets with different free gossypol contents in the testicular morphometry and semen quality of Nelore bulls. 28 bulls were randomly distributed in six treatments: T0, receiving no free gossypol; T1, receiving 1.08g / bull / day; T2, receiving 2.07g / bull / day; T3, receiving 3.24g / bull / day; T4, receiving 3.82g / bull / day and T5, receiving 5.08g / bull / day of free gossypol respectively. The animals in each treatment were kept confined in an averaged area of 100m2, having fresh water, troughs for mineral mixture and roughage / concentrate. The consumption of 3.24g of free gossypol / bull / day altered the bulls sperm quality and testicular morphometry.(AU)
Subject(s)
Animals , Male , Cattle , Testis/anatomy & histology , Cottonseed Oil/administration & dosage , Gossypol/administration & dosage , Semen Analysis , Infertility, Male/veterinaryABSTRACT
A cotonicultura tem forte fator de impacto na economia nacional, e o estado de Mato Grosso se destaca por ser o maior produtor de algodão herbáceo e deter o maior rebanho bovino do país, condições essas que estimulam o uso do caroço, da torta e do farelo de algodão na alimentação animal. Considerando que o gossipol está presente nos subprodutos do algodão e que seus efeitos sobre a reprodução podem reduzir a fertilidade dos animais, objetivou-se, com essa pesquisa, avaliar o efeito da ingestão de dietas com diferentes teores de gossipol livre por dia sobre a morfometria testicular e a qualidade seminal de touros da raça Nelore. Foram utilizados 28 touros, distribuídos aleatoriamente em seis tratamentos: T0, 0 grama de gossipol livre/touro/dia ; T1, 1,08 grama de gossipol livre/touro/dia; T2, 2,07 gramas de gossipol livre/touro/dia; T3, 3,24 gramas de gossipol livre/touro/dia; T4, 3,82 gramas de gossipol livre/touro/dia e T5, 5,08 gramas de gossipol livre/touro/dia. Os animais de cada tratamento foram mantidos confinados em área média de 100m2, dotada de bebedouro, cochos para mistura mineral e para volumoso/concentrado. O consumo de 3,24 gramas de gossipol livre/touro/dia alterou a qualidade espermática e a morfometria testicular de touros.(AU)
The cotton industry has a strong impact factor in the Brazilian economy and the state of Mato Grosso stands out for being the largest upland-type cotton producer and also holds the largest cattle herd in the country, conditions that stimulate the use of cottonseed pie and cottonseed meal in animal feed. Whereas gossypol is present in cotton by-products and their effects on reproduction can reduce the animal fertility, this research evaluated the effect of diets with different free gossypol contents in the testicular morphometry and semen quality of Nelore bulls. 28 bulls were randomly distributed in six treatments: T0, receiving no free gossypol; T1, receiving 1.08g / bull / day; T2, receiving 2.07g / bull / day; T3, receiving 3.24g / bull / day; T4, receiving 3.82g / bull / day and T5, receiving 5.08g / bull / day of free gossypol respectively. The animals in each treatment were kept confined in an averaged area of 100m2, having fresh water, troughs for mineral mixture and roughage / concentrate. The consumption of 3.24g of free gossypol / bull / day altered the bulls sperm quality and testicular morphometry.(AU)
Subject(s)
Animals , Male , Cattle , Testis/anatomy & histology , Cottonseed Oil/administration & dosage , Gossypol/administration & dosage , Semen Analysis , Infertility, Male/veterinaryABSTRACT
The aim of the present study was to analyze seminal quality of young bulls subjected to different frequencies of gossypol supplementation. Forty-eight Nellore bulls, with 19 months of age and weighing 357.8⯱â¯7.2â¯kg, were used in this study. Animals were fed with 10.5â¯kg of standard supplement containing free-gossypol from whole cottonseed (WCS) at the following frequency: 3x/week (G3x), 5x/week (G5x) or 7x/week (G7x - Control). Additionally, a negative control was provided, and the treated animals received only mineral supplement (MM) ad libtum. The experiment lasted for 84 days and semen was collected at the beginning and at the end for analysis and cryopreservation. Fresh semen was used for initial analysis and plasma membrane integrity and sperm morphology were also determined. General motility using computer assisted sperm analysis (CASA), plasma and acrosomal membranes integrity, mitochondrial activity, and induced oxidative stress were assessed in post-thawed semen. The study design was completely randomized. Parametric data were analyzed by ANOVA and non-parametric data by the Wilcoxon test, using the statistical program SAS. Level of significance was set at 5%. Supplementation with WCS, regardless the frequency, increased total (Pâ¯=â¯.009) and head (Pâ¯=â¯.005) defects in comparison to animals receiving only forage and mineral supplement. Infrequent supplementation, particularly 5 times in the week (G5X), increased head (Pâ¯=â¯.026) and midpiece (Pâ¯=â¯.014) abnormalities. Sperm motility in fresh semen was lower in animals that received daily supplementation than those supplemented on alternate days (Pâ¯=â¯.021). Additionally, animals supplemented daily showed lower percentage of spermatozoa with intact acrosome compared to those supplemented on alternate days (Pâ¯=â¯.005). Thus, regardless the frequency of supplementation, free-gossypol supplementation affects sperm quality. Although the amount of free gossypol supplied weekly was the same among treatments, daily supplementation compromised sperm kinetics, differently from infrequent supplementation that led to sperm defects developed during spermatogenesis.
Subject(s)
Animal Feed , Cattle , Gossypol/administration & dosage , Gossypol/toxicity , Reproduction/drug effects , Animal Feed/toxicity , Animal Nutritional Physiological Phenomena , Animals , Cryopreservation/methods , Cryopreservation/veterinary , Dietary Supplements , Dose-Response Relationship, Drug , Drug Administration Schedule , Male , Semen/cytology , Semen/drug effects , Semen Analysis/veterinary , Semen Preservation/veterinary , Sexual Maturation/drug effects , Spermatogenesis/drug effectsABSTRACT
AT-101 is a BH3 mimetic and pan-Bcl-2 inhibitor that has shown potent anticancer activity in non-small-cell lung cancer (NSCLC) in murine models, but failed to show clinical efficacy when used in combination with docetaxel in NSCLC patients. Our recent study has demonstrated that AT-101 enhanced the antitumor effect of cisplatin (CDDP) in a murine model of NSCLC via inhibition of the interleukin-6/signal transducer and activator of transcription 3 (STAT3) pathway. This study explored the underlying mechanisms for the enhanced anticancer activity of CDDP by AT-101. Our results show that, when compared with monotherapy, AT-101 significantly enhanced the inhibitory effects of CDDP on proliferation and migration of A549 cells and on tube formation and migration in human umbilical vein endothelial cells. AT-101 promoted the proapoptotic activity of CDDP in A549 cells. AT-101 also enhanced the inhibitory effect of CDDP on DNA repair and redox activities of apurinic/apyrimidinic endonuclease 1 (APE1) in A549 cells. In tumor tissues from nude mice treated with AT-101 plus CDDP or monotherapy, the combination therapy resulted in greater inhibition of angiogenesis and tumor cell proliferation than the monotherapy. These results suggest that AT-101 can enhance the antitumor activity of CDDP in NSCLC via inhibition of APE1 DNA repair and redox activities and by angiogenesis and induction of apoptosis, but other mechanisms cannot be excluded. We are now conducting a Phase II trial to examine the clinical efficacy and safety profile of combined use of AT-101 plus CDDP in advanced NSCLC patients.
Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/pharmacology , Gossypol/analogs & derivatives , Lung Neoplasms/drug therapy , Animals , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Cisplatin/administration & dosage , DNA Repair/drug effects , DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism , Gossypol/administration & dosage , Gossypol/pharmacology , Human Umbilical Vein Endothelial Cells , Humans , Lung Neoplasms/pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Neovascularization, Pathologic/drug therapy , Oxidation-Reduction/drug effects , Xenograft Model Antitumor AssaysABSTRACT
Gossypol is a highly reactive compound present in cotton (Gossypium spp.). The aim of this work was to determine whether the administration of gossypol conjugated to albumin can immunize rats and thereby prevent the acute hepatotoxicity associated with gossypol. The first experiment consisted of administering the immunogen gossypol-BSA, with or without the Freund's incomplete adjuvant, to rats. The production of antibodies against gossypol was subsequently verified. The second experiment comprised three groups of Wistar rats: VG, CG and CO. The rats from the VG cohort were injected with gossypol-BSA associated with Freund's incomplete adjuvant, and the animals from the CG and CO groups were injected with saline solution. After 21 days, the rats from the VG and CG cohorts were treated with 30 mg/kg of gossypol by intraperitoneal injection, whereas the rats from the CO group received corn oil. After 24 h, the rats were evaluated for clinical signs of pathology, and their serum was biochemically analyzed. It was found that gossypol promoted hepatotoxic effects that were not prevented by the administration of gossypol-BSA. In conclusion, the administration of gossypol-BSA associated with Freund's incomplete adjuvant may be lightly to prevent the acute hepatotoxicity associated with gossypol.
Subject(s)
Chemical and Drug Induced Liver Injury/prevention & control , Gossypol/adverse effects , Immunoconjugates/pharmacology , Serum Albumin, Bovine/pharmacology , Acute Disease , Animals , Antibodies/blood , Chemical and Drug Induced Liver Injury/pathology , Female , Freund's Adjuvant/administration & dosage , Gossypol/administration & dosage , Immunization , Immunoconjugates/administration & dosage , Injections, Intraperitoneal , Lipids/administration & dosage , Male , Rats , Rats, Wistar , Serum Albumin, Bovine/administration & dosageABSTRACT
O fígado desempenha uma função central no metabolismo devido à sua interposição entre o trato digestivo e a circulação geral do organismo. Ele é também o principal órgão envolvido na biotransformação de substâncias exógenas (xenobióticos), com capacidade de converter compostos hidrofóbicos em hidrossolúveis, mais facilmente eliminados pelo organismo. O gossipol é uma substância fenólica tóxica presente na semente de algodão (Gossypium sp). Com o objetivo de estudar os mecanismos envolvidos na hepatotoxicidade do gossipol avaliou-se os seus efeitos no sistema antioxidante do fígado de ratos no que diz respeito ao estresse oxidativo e aspectos histopatológicos. Foram utilizados ratos machos da linhagem Wistar, separados em dois grupos, sendo que um recebeu óleo de canola (veículo, grupo Controle) e o outro recebeu gossipol na dosagem de 40 mg/kg de peso vivo do animal por 15 dias (grupo Tratado). O tratamento com gossipol promoveu alterações na atividade sérica das enzimas marcadoras de dano hepático e um significativo estresse oxidativo caracterizado pela diminuição nos níveis da glutationa reduzida (GSH) e consequente aumento da glutationa oxidada (GSSG), incluindo, ainda, danos à membrana plasmática e de organelas demonstrados pela peroxidação lipídica. O resultado da avaliação histopatológica demonstrou degeneração dos hepatócitos.
The liver plays a central role in metabolism due to its interposition between the digestive tract and the general circulation of the organism. It is also the main organ involved in biotransformation of exogenous substances (xenobiotics), with ability to convert hydrophobic compounds in water-soluble, more easily eliminated by the body. Gossypol is a toxic phenolic substance present in cotton seed (Gossypium sp.). Aiming to study the mechanisms involved in the hepatotoxicity of gossypol we evaluate its effects on the antioxidant system of rat liver performing an experiment that investigated the oxidative stress and the histopathological alterations. In this study, we used Wistar rats, divided into two groups, one that received canola oil (vehicle, Control group) and another that received gossypol at a dose of 40mg/kg body weight of the animal for 15 days (Treated group). The treatment with gossypol caused alterations in the activity of seric enzymes that indicate hepatic injury and a significant oxidative stress characterized by a decrease of reduced glutathione (GSH) levels and a consequent increase in oxidized glutathione (GSSG), including further damage to the plasma membrane and organelles showed by lipid peroxidation. The result of histopathological evaluation showed degeneration of the hepatocytes.
Subject(s)
Animals , Mice , Liver/physiopathology , Glutathione , Gossypol/administration & dosage , Oxidative Stress , Rats, Wistar , Brassica napus/adverse effects , Gossypol/adverse effects , Gossypol/toxicity , MetabolismABSTRACT
O fígado desempenha uma função central no metabolismo devido à sua interposição entre o trato digestivo e a circulação geral do organismo. Ele é também o principal órgão envolvido na biotransformação de substâncias exógenas (xenobióticos), com capacidade de converter compostos hidrofóbicos em hidrossolúveis, mais facilmente eliminados pelo organismo. O gossipol é uma substância fenólica tóxica presente na semente de algodão (Gossypium sp). Com o objetivo de estudar os mecanismos envolvidos na hepatotoxicidade do gossipol avaliou-se os seus efeitos no sistema antioxidante do fígado de ratos no que diz respeito ao estresse oxidativo e aspectos histopatológicos. Foram utilizados ratos machos da linhagem Wistar, separados em dois grupos, sendo que um recebeu óleo de canola (veículo, grupo Controle) e o outro recebeu gossipol na dosagem de 40 mg/kg de peso vivo do animal por 15 dias (grupo Tratado). O tratamento com gossipol promoveu alterações na atividade sérica das enzimas marcadoras de dano hepático e um significativo estresse oxidativo caracterizado pela diminuição nos níveis da glutationa reduzida (GSH) e consequente aumento da glutationa oxidada (GSSG), incluindo, ainda, danos à membrana plasmática e de organelas demonstrados pela peroxidação lipídica. O resultado da avaliação histopatológica demonstrou degeneração dos hepatócitos.(AU)
The liver plays a central role in metabolism due to its interposition between the digestive tract and the general circulation of the organism. It is also the main organ involved in biotransformation of exogenous substances (xenobiotics), with ability to convert hydrophobic compounds in water-soluble, more easily eliminated by the body. Gossypol is a toxic phenolic substance present in cotton seed (Gossypium sp.). Aiming to study the mechanisms involved in the hepatotoxicity of gossypol we evaluate its effects on the antioxidant system of rat liver performing an experiment that investigated the oxidative stress and the histopathological alterations. In this study, we used Wistar rats, divided into two groups, one that received canola oil (vehicle, Control group) and another that received gossypol at a dose of 40mg/kg body weight of the animal for 15 days (Treated group). The treatment with gossypol caused alterations in the activity of seric enzymes that indicate hepatic injury and a significant oxidative stress characterized by a decrease of reduced glutathione (GSH) levels and a consequent increase in oxidized glutathione (GSSG), including further damage to the plasma membrane and organelles showed by lipid peroxidation. The result of histopathological evaluation showed degeneration of the hepatocytes.(AU)
Subject(s)
Animals , Mice , Rats, Wistar , Liver/physiopathology , Gossypol/administration & dosage , Oxidative Stress , Glutathione , Gossypol/adverse effects , Gossypol/toxicity , Brassica napus/adverse effects , MetabolismABSTRACT
This study evaluated the semen quality of Santa Ines sheep fed diets containing different levels of whole cottonseed (WCS). Twenty sheep were distributed into four groups that were given diets with 0; 20; 30; 40% of WCS. For this study the semen was collected by electroejaculation, and a monthly andrological examination was performed during nine months. The analyzed variables were: scrotal circumference (SC), appearance and color of the ejaculate, progressive motility (PM), vigor, mass movement (MM), total sperm concentration (spzX109 ), sperm morphology (SM) and blood hematocrit. The SC had no difference among diets, with mean 31.83 cm. The animals fed diets with WCS, presented mean intake of 9.16 mg gossypol kg BW, and were prone to present greenish semen, and appearance ranging from thin creamy to watery. The PM decreased linearly (p < 0.05) with increasing level of WCS, while the vigor had a quadratic trend. The total defects increased linearly in relation to reference values described in literature. The WSC had no influence on hematocrit levels, but did affect the PM and vigor of spermatozoa, thus not recommended to diets of animals for breeding.
Este estudo objetivou avaliar a qualidade do sêmen de carneiros da raça Santa Inês, alimentados com dietas contendo diferentes níveis de caroço de algodão integral (CAI). Foram utilizados 20 carneiros distribuídos em quatro dietas e alimentados com 0, 20, 30, 40% do caroço de algodão integral. Para este estudo realizou-se a coleta de sêmen dos animais pelo método da eletroejaculação e durante nove meses procedeu-se o exame andrológico mensal. As variáveis analisadas foram: circunferência escrotal (CE); volume, aspecto e cor do ejaculado, motilidade progressiva (MP), vigor, movimento de massa (MM), concentração espermática total (spzX109 ), morfologia espermática (ME) e hematócritos sanguíneos. A CE não variou entre as dietas com média de 31,83 cm. Os animais que receberam (CAI) tiveram ingestão média de 9,16 mg de gossipol kg-1 PV, e tenderam a apresentar o sêmen de coloração esverdeada, com aspecto variando de cremoso fino a aquoso. Nas características microscópicas a MP decresceu linearmente com aumento do nível de CAI, enquanto o vigor mostrou comportamento quadrático. Os defeitos totais tiveram efeito linear crescente em relação aos valores de referência descritos na literatura. O CAI não influenciou os níveis de hematócritos, porém afetou a motilidade progressiva e o vigor dos espermatozoides, não devendo ser usado em dietas de animais destinados à reprodução.
Subject(s)
Animals , Gossypol/administration & dosage , Sheep , Diet , Semen AnalysisABSTRACT
The aim of this study was to determine how gossypol affects the viability and activity of polymorphonuclear leukocytes and monocytes in blood obtained from healthy donors. Loss of mitochondrial membrane potential (delta psi m) and apoptosis was maximized in human polymorphonuclear leukocytes and monocytes after incubation with gossypol. Pretreatment with a caspase-9 inhibitor or antioxidants (superoxide dismutase or Trolox) inhibited gossypol-induced loss of the delta psi m and apoptosis. Likewise, we observed participation of caspase -3, -7, and -10 in gossypol-induced apoptosis. Expression of the proapoptotic genes bax, bak, bad and p53/Tp53 increased in polymorphonuclear leukocytes exposed to gossypol. The expression of the anti-apoptotic genes bcl-(XL) and mcl-1 was reduced when polymorphonuclear leukocytes and monocytes were treated with gossypol. Gossypol treatment also inhibited yeast phagocytosis by these cells. We concluded that gossypol induces apoptosis in phagocytic cells and that this effect was dose-dependent. The findings in this report may be important to consider in light of possible gossypol use in clinical strategies for cancer treatment.
Subject(s)
Apoptosis/drug effects , Gossypol/administration & dosage , Mitochondria/drug effects , Monocytes/drug effects , Neutrophils/drug effects , Reactive Oxygen Species/metabolism , Adult , Antioxidants/metabolism , Caspases/metabolism , Chromans/metabolism , Cyclin D1/biosynthesis , Female , Humans , Male , Membrane Potential, Mitochondrial/drug effects , Myeloid Cell Leukemia Sequence 1 Protein , Phagocytosis/drug effects , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Superoxide Dismutase/metabolism , Tumor Suppressor Protein p53/biosynthesis , Young Adult , bcl-2 Homologous Antagonist-Killer Protein/biosynthesis , bcl-2-Associated X Protein/biosynthesis , bcl-Associated Death Protein/biosynthesisABSTRACT
Gossypol is a polyphenol isolated from the seed, roots, and stem of the cotton plant (Gossypium sp.). The substance, a yellow pigment similar to flavonoids, is present in cottonseed oil. In the plant, it acts as a natural defensive agent against predators, provoking infertility in insects. In most animals, gossypol provokes infertility, and in man it causes spermatogenesis arrest at relatively low doses. Studies carried out in China, Africa, and Brazil have shown that the substance is well tolerated, causing no side effects that lead to discontinuation. The reported hypokalemia of early studies has not been confirmed in the latest trials. The only concern at present appears to be lack of reversibility in over 20% of subjects. Gossypol should be prescribed preferably to men who have completed their families or for those who would accept permanent infertility after a few years of use.
Subject(s)
Contraceptive Agents, Male , Gossypol , Animals , Antispermatogenic Agents/pharmacology , Contraceptive Agents, Male/administration & dosage , Contraceptive Agents, Male/adverse effects , Contraceptive Agents, Male/pharmacology , Gossypol/administration & dosage , Gossypol/adverse effects , Gossypol/pharmacology , Infertility, Male/chemically induced , Male , Spermatogenesis/drug effectsABSTRACT
The safety and efficacy of gossypol continues to be controversial. The aim of this study was to evaluate gossypol as a contraceptive pill for men at doses lower than those previously prescribed and in men from various ethnic origin. A total of 151 men from Brazil, Nigeria, Kenya, and China were divided into two groups. Both groups received 15 mg gossypol/day for 12 or 16 weeks to reach spermatogenesis suppression. Subjects were then randomized to either 7.5 or 10 mg/day for 40 weeks. In addition, 51 men were enrolled as a control group. In all, 81 subjects attained spermatogenesis suppression. Only one man discontinued treatment because of tiredness. Potassium levels fluctuated within the normal range. FSH increased consistently. Testicular volume decreased, but after discontinuation, values returned to levels not statistically different from admission. Of 19 subjects on the 7.5 mg/day dose group, 12 recovered sperm counts >20 million/mL within 12 months of discontinuing gossypol. In the 10 mg/day group, sperm counts recovered in only 10 of 24 subjects. Eight of the 43 patients remained azoospermic 1 year after stopping gossypol. All men diagnosed with varicocele failed to reverse spermatogenesis suppression. Gossypol blood levels indicated that sperm suppression occurs independently of concentration, whereas spermatogenesis recovery appears to be concentration-dependent. Gossypol may become a medical alternative to surgical vasectomy when the delay in onset of infertility is acceptable. When taken for 1 year, gossypol causes no reduction in sexual desire or frequency of intercourse. The possibility of reversal, occurring in 51% of the men on this regimen within 1 year after stopping gossypol, is an advantage of this compound as compared with surgical sterilization in many parts of the world.
PIP: The safety and efficacy of gossypol continues to be controversial. The aim of this study was to evaluate gossypol as a contraceptive pill for men at doses lower than those previously prescribed and in men from various ethnic origin. A total of 151 men from Brazil, Nigeria, Kenya, and China were divided into two groups. Both groups received 15 mg gossypol/day for 12 or 16 weeks to reach spermatogenesis suppression. Subjects were then randomized to either 7.5 or 10 mg/day for 40 weeks. In addition, 51 men were enrolled as a control group. In all, 81 subjects attained spermatogenesis suppression. Only 1 man discontinued treatment because of tiredness. Potassium levels fluctuated within the normal range. FSH increased consistently. Testicular volume decreased, but after discontinuation, values returned to levels not statistically different from admission. Of 19 subjects in the 7.5 mg/day dose group, 12 recovered sperm counts higher than 20 million/ml within 12 months of discontinuing gossypol. In the 10 mg/day group, sperm counts recovered in only 10 of 24 subjects. 8 of the 43 patients remained azoospermic 1 year after stopping gossypol. All men diagnosed with varicocele failed to reverse spermatogenesis suppression. Gossypol blood levels indicated that sperm suppression occurs independently of concentration, whereas spermatogenesis recovery appears to be concentration-dependent. Gossypol may become a medical alternative to surgical vasectomy when the delay in onset of infertility is acceptable. When taken for 1 year, gossypol causes no reduction in sexual desire or frequency of intercourse. The possibility of reversal, occurring in 51% of the men on this regimen within 1 year after stopping gossypol, is an advantage of this compound as compared with surgical sterilization in many parts of the world.
Subject(s)
Contraceptive Agents, Male/blood , Gossypol/blood , Spermatogenesis/drug effects , Adult , Brazil , China , Contraceptive Agents, Male/administration & dosage , Contraceptive Agents, Male/adverse effects , Follicle Stimulating Hormone/blood , Gossypol/administration & dosage , Gossypol/adverse effects , Humans , Kenya , Kinetics , Male , Nigeria , Potassium/blood , Testis/anatomy & histologyABSTRACT
Se captaron 13 hombres voluntarios menores de 45 años, que habían solicitado vasectomia y no tenían contradicciones para el uso del medicamento. Los sujetos recibieron 10 mg diarios de gosipol por vía oral durante la fase de saturación (3 meses) y 10 mg 3 meses por semana durante la fase de mantenimiento (de 13 a 14 meses). Se relizó interrogatorio y examen físico en la visita de admición y en las de seguimiento, así como monitoreo de la concentración de potasio, enzimas hepáticas, electrocardiograma, indicadores de la función renal, espermograma y determinación de los niveles sanguineos de las hormonas relacionadas con la reproducción. Se descontinuaron del estudio 6 sujetos .De los 7 que terminaron el ensayo ,4 bajaron de peso y 2 aumentaron la proteinuria. Se obsevó una gran iregularidad en el patrón de respuesta del espermograma. No se hallaron cambios en los niveles de T, DTH, E2, FSH, LH y PRL. En conclusión, el regimen de bajas dosis de gosipol como contraceptivo masculino no es muy eficaz, mantiene efectos tóxicos secundarios en algunos casos y no actúa sobre las hormonas más importantes de la reproducción; ello sugiere que éste no es un método contraceptivo masculino útil para grandes poblaciones