Effects of gossypol from cottonseed cake on the blood profile in sheep.

Cottonseed cake contains gossypol, a potentially toxic compound that, when consumed by sheep, can affect reproduction, the immune system, and the liver. Changes in hematologic and serum biochemical parameters were monitored for 63 days in 12 Santa Inês ewes, six of which received ration containing 400 g kg(-1) of cottonseed cake. Blood samples were collected at the start of the experiment and weekly thereafter for hematologic assessment and determination of serum urea, creatinine, total protein, and albumin concentrations and for measurement of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transferase activities. No clinical signs of toxicity were observed. Evaluation of the erythron showed that sheep consuming cottonseed cake had an increased packed cell volume (p < 0.05) and increased erythrocyte counts and hemoglobin concentrations (p < 0.05) in the leukogram and serum biochemistry panel. In conclusion, consumption of 400 g kg(-1) cottonseed cake by sheep for 63 days may induce changes in the erythron but no consistent changes in serum biochemical parameters, indicating no damage to the liver or kidneys.

Mechanisms involved in reproductive damage caused by gossypol in rats and protective effects of vitamin E.

BACKGROUND: Gossypol is a chemical present in the seeds of cotton plants (Gossypium sp.) that reduces fertility in farm animals. Vitamin E is an antioxidant and may help to protect cells and tissues against the deleterious effects of free radicals. The aim of this study was to evaluate the mechanisms of reproductive toxicity of gossypol in rats and the protective effects of vitamin E. Forty Wistar rats were used, divided into four experimental groups (n = 10): DMSO/saline + corn oil; DMSO/saline + vitamin E; gossypol + corn oil; and gossypol + vitamin E. RESULTS: Fertility was significantly reduced in male rats treated with gossypol in that a significant decrease in epididymal sperm count was observed (P < 0.05) and the number of offspring was significantly reduced in females mated with them (P < 0.05). This dysfunction was prevented by vitamin E. Gossypol caused a significant increase in the activity of the enzymes glutathione peroxidase (P < 0.01) and glutathione reductase (P < 0.01), but vitamin E did not reduce the enzyme activities (P > 0.05). The levels of reduced glutathione and pyridine nucleotides in testis homogenate were significantly reduced by gossypol (P < 0.05 and P < 0.01, respectively) and this reduction was accompanied by increased levels of oxidized glutathione (P < 0.05). Vitamin E showed a preventive effect on the changes in the levels of these substances. Gossypol significantly increased the levels of malondialdehyde (P < 0.01), a lipid peroxidation indicator, whereas treatment with vitamin E inhibited the action of the gossypol. Vitamin E prevented a decrease in mitochondrial ATP induced by gossypol (P < 0.05). CONCLUSIONS: This study suggests that the reproductive dysfunction caused by gossypol may be related to oxidative stress and mitochondrial bioenergetic damage and that treatment with vitamin E can prevent the infertility caused by the toxin.

Mechanisms involved in reproductive damage caused by gossypol in rats and protective effects of vitamin E

BACKGROUND: Gossypol is a chemical present in the seeds of cotton plants (Gossypium sp.) that reduces fertility in farm animals. Vitamin E is an antioxidant and may help to protect cells and tissues against the deleterious effects of free radicals. The aim of this study was to evaluate the mechanisms of reproductive toxicity of gossypol in rats and the protective effects of vitamin E. Forty Wistar rats were used, divided into four experimental groups (n = 10): DMSO/ saline + corn oil; DMSO/saline + vitamin E; gossypol + corn oil; and gossypol + vitamin E. RESULTS: Fertility was significantly reduced in male rats treated with gossypol in that a significant decrease in epididy-mal sperm count was observed (P < 0.05) and the number of offspring was significantly reduced in females mated with them (P < 0.05). This dysfunction was prevented by vitamin E. Gossypol caused a significant increase in the activity of the enzymes glutathione peroxidase (P < 0.01) and glutathione reductase (P < 0.01), but vitamin E did not reduce the enzyme activities (P > 0.05). The levels of reduced glutathione and pyridine nucleotides in testis homogen-ate were significantly reduced by gossypol (P < 0.05 and P < 0.01, respectively) and this reduction was accompanied by increased levels of oxidized glutathione (P < 0.05). Vitamin E showed a preventive effect on the changes in the levels of these substances. Gossypol significantly increased the levels of malondialdehyde (P < 0.01), a lipid peroxida-tion indicator, whereas treatment with vitamin E inhibited the action of the gossypol. Vitamin E prevented a decrease in mitochondrial ATP induced by gossypol (P < 0.05). CONCLUSIONS: This study suggests that the reproductive dysfunction caused by gossypol may be related to oxidative stress and mitochondrial bioenergetic damage and that treatment with vitamin E can prevent the infertility caused by the toxin.

Gossypol promotes degeneration of ovarian follicles in rats.

The present study aimed to determine if gossypol interferes with ovarian follicles in rats. Twenty-four female Wistar rats were assigned to two equal groups: one control group and the other dosed with gossypol (25 mg/kg/day, subcutaneously) for 15 days. Ovarian follicles were histologically classified according to the stage of development and as normal or atretic. Gossypol treatment reduced the length of estrous with an increase in the duration of the diestrus phase. This compound was responsible for reduced serum levels of T4 and progesterone. Treatment with gossypol was responsible for a significant reduction in the number of normal ovarian follicles and a significant increase in the number of atretic follicles, both in all stages of development. Thus, treatment of rats with gossypol was responsible for reduction in the number of viable follicles and changes in hormone levels that resulted in interference of the estrous cycle.

Effectiveness of albumin-conjugated gossypol as an immunogen to prevent gossypol-associated acute hepatotoxicity in rats.

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.

Mecanismos da intoxicação do fígado de rato causada pelo gossipol / Mechanisms of the intoxication of rat liver caused by gossypol

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.

Mecanismos da intoxicação do fígado de rato causada pelo gossipol / Mechanisms of the intoxication of rat liver caused by gossypol

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)

Gossypol: a contraceptive for men.

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.

Gossypol blood levels and inhibition of spermatogenesis in men taking gossypol as a contraceptive. A multicenter, international, dose-finding study.

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.

Desarrollo y evaluación de un panqué enriquecido con harina de algodón / Development and evaluation of an enriched cake with cottonsedd meal

En Venezuela, los problemas nutricionales, específicamente la desnutrición caloricoproteica, se ha acentuado en los últimos años. Una posible solución lo constituye el enriquecimiento de alimentos con fuentes de proteínas, como las que contiene el residuo o torta de la extracción del aceite de las semillas de algodón. En este trabajo se caracterizaron las harinas de algodón obtenidas industrialmente y se utilizó hasta en un 15 por ciento en un panqué enriquecido, susceptible a ser utilizado en la merienda escolar. Se seleccionó el panqué de vainilla con 45 por ciento de harina de algodón debido a que la aceptabilidad a nivel de laboratorio fue de 97 por ciento. Se probó en una escuela con 1.009 niños de distintas edades, la aceptabilidad fue de 97 por ciento. Se concluyó que este producto, que suministra 395 Kcal y 13 g de proteínapor cada 100 g, podría ser utilizado para mejorar el aporte calóricoproteico de la merienda escolar

Ensayo clínico con gosipol en bajas dosis como contraceptivo masculino / Clinical trial with gosipol in low dose as male contraceptive

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

Ensayo clínico con gosipol en bajas dosis como contraceptivo masculino / Clinical trial with gosipol in low dose as male contraceptive

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