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.

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.

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