Gossypol

Gossypol exits in two different forms, free form and total form in cotton seeds. However, both the forms of gossypol can be toxic to animals which limit the usefulness of cottonseed as animal feed. The present investigation deals with estimation of total and free gossypol content from different Bt and non-Bt cotton varieties. Gossypol content of various seeds extracts of Bt and non-Bt of cotton varieties was conducted through an improved HPLC. Among the all Non-Bt varieties, JKCH 2245 had shown higher amount of total gossypol 2068 mg/kg and free gossypol of 4140mg/kg and Bt variety RCH-779 BG-II had shown lower amount of total gossypol 919 mg/kg and free gossypol 1814 mg/kg. Non-Bt varieties had shown less gossypol content and these accessions were advised for farmers to enhance their export demands. This can be helpful to the cotton seed oil industries in India for exporting gossypol free cotton seed oil.

Gossypol is a phenolic compound produced by pigment glands in cotton stems, leaves, seeds, and flower buds (Gossypium spp.). Cottonseed meal is a by-product of cotton that is used for animal feeding because it is rich in oil and proteins. However, gossypol toxicity limits cottonseed use in animal feed. High concentrations of free gossypol may be responsible for acute clinical signs of gossypol poisoning which include respiratory distress, impaired body weight gain, anorexia, weakness, apathy, and death after several days. However, the most common toxic effects is the impairment of male and female reproduction. Another important toxic effect of gossypol is its interference with immune function, reducing an animal's resistance to infections and impairing the efficiency of vaccines. Preventive procedures to limit gossypol toxicity involve treatment of the cottonseed product to reduce the concentration of free gossypol with the most common treatment being exposure to heat. However, ...

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.

The chromosome-damaging potential of gossypol was evaluated by scoring sister chromatid exchanges (SCEs), determining the percentage of pulverized metaphases and the mitotic index in bone marrow cells of mice. Bone marrow cells were collected approximately 21 hours after the intraperitoneal (0,20,40,80, or 160 micrograms/g) and oral (0,40,80, or 160 micrograms/g) administration of gossypol acetic acid. Irrespective of the dosing schedule (single or multiple doses), the vehicle used (physiological saline, corn oil, or 10% aqueous ethanol), and the route of administration, the mean SCE count per cell was significantly higher (P less than 0.05) in gossypol-treated groups than their control counterparts. At 80 and 160 micrograms/g dose levels, the occurrence of metaphase chromosome pulverization was significantly greater, while mitotic index values were markedly lower than those of the corresponding control values. The results suggest that gossypol is a potentially mutagenic and clastogenic agent in murine bone marrow cells.

An experiment was conducted to determine the effects of long-term feeding of cottonseed meal on the reproductive traits of Holstein bulls. Holstein bulls approximately 6 mo of age were placed on the following treatments: 1) soybean meal + corn (CON); 2) cottonseed meal + corn (GOS); and 3) cottonseed meal + 4,000 IU vitamin E x bull(-1) x d(-1) (G+4E). The GOS and G+4E diets were formulated to supply 14 mg of free gossypol x kg(-1) BW x d(-1). These bulls had been in a previous experiment that evaluated the effects of feeding the same type of diets, but from 2 wk to 6 mo. of age. Percentage of motility, percentage of normal and live sperm, and daily sperm production were less (P<.05) in the GOS than in the other two treatments. Percentages of primary abnormalities and abnormal midpieces were greater (P<.05) in the GOS group than in the other two groups. At 12 and 16 mo. of age, bulls were given two assessments for sex drive traits. Bulls that received gossypol exhibited less s...

Prolactin (PRL) has been reported to stimulate citrate production and the activity of mitochondrial aspartate aminotransferase (mAAT) and its precursor form pmAAT in prostate epithelial cells. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) caused the same result as PRL, which suggests that the PRL effect on mAAT activity might be mediated by protein kinase C (PKC) stimulation of pmAAT gene transcription. Both PRL and TPA increased the level of pmAAT mRNA by 2.5- to 3-fold in pig prostate cells. The PKC inhibitor gossypol completely inhibited the PRL and TPA induced increases. In addition, the effects of both PRL and TPA were inhibited by down-regulation of prostate PKC. Nuclear run-off assays indicated that PRL and TPA induction of pmAAT occurred primarily at the transcriptional level. The stimulation of pmAAT transcription by TPA suggests that the pmAAT gene contains a TPA response element. Thus, these results are consistent with our previous observation that PRL dire...

A simple method for the simultaneous analysis of normetanephrine, metanephrine and 3-methoxytyramine (both free and conjugated) in human urine by reversed-phase ion-pair high-performance liquid chromatography with electrochemical detection has been developed. Existing methods have been optimized for extraction by study of analytic parameters. The hydrolysed urines are purified and concentrated by successive passages on two ion-exchange resins and ammoniacal elution to eliminate interference from pigments or related chemical compounds. The methoxyamines are separated by high-performance liquid chromatography on a reversed-phase column. Detection and quantitation are achieved with an electrochemical detector using a vitreous carbon electrode. Samples can be injected at 25-min intervals. Reference values of adults and children are given.

The selectivity of hexane isomers towards cottonseed pigments and colour fixed pigments was illustrated by using spectrophotometric analysis of crude, refined and bleached oils, and by refinability and bleachability criteria. Crude cottonseed oil contains besides the alkali-refinable gossypol and gossypurpurin, several colour fixed pigments. Anhydrogossypol, gossyfulvin, anthocyanins and carotenoids seem to be responsible for the colour-fixation of the oil. Only carotenoids are eliminated by bleaching. Selectivities of hexane isomers towards colour fixed pigments are in the following order: isohexane < n-hexane < cyclohexane < benzene < methylcyclopentane.

Owing to the high levels of antiapoptotic B-cell lymphoma 2 (BCL-2) family members observed in several cancers, there has been a major effort to develop inhibitors of the BCL2-family as chemotherapeutic agents. Of the different members in the BCL-2 family, myeloid cell leukemia sequence 1 (MCL-1) is commonly amplified in human tumors and is associated with their relapse and chemoresistance. As a result, specific inhibitors of MCL-1 are being designed to treat resistant tumors. However, there is increasing evidence for other nonapoptotic roles of the BCL-2 family, ranging from ionic homeostasis and autophagy to the regulation of fission-fusion dynamics in subcellular organelles, including the endoplasmic reticulum and mitochondria. In this study, we characterize the specificity of two novel putative MCL-1 inhibitors, BI97C1 (Sabutoclax) and BI112D1, in inducing apoptosis in a BAX/BAK-dependent manner and in an MCL-1-dependent system. In addition to their being proapoptotic, these inh...

Abstract
Cottonseed and its by-products are used extensively for supplementing ruminant rations. However, they contain gossypol which is a reproductive toxicant in males of both ruminant and non-ruminants. This study evaluated the effects of dietary gossypol from whole cottonseed and cottonseed cake on the semen characteristics of Yankasa rams. Fifteen (15) Yankasa rams weighing an average of 20 ± 3 Kg were randomly distributed into three groups (A, B and C) of five rams each and were fed diets containing 48% whole cottonseed, 48% cottonseed and control diet (gossypol-free), respectively for 14 weeks. The semen was collected weekly using an electro-ejaculator and was evaluated for volume, gross motility, concentration; live sperm cells and morphology were evaluated on a weekly basis. The data obtained were statistically analysed using GraphPad Prism version 5.0. Significance of differences between treatments means were determined at P ≤ 0.05 with Tukey-Kramer multiple comparison test of repeated measure analysis of variance (ANOVA). The mean semen volume and concentration of the rams in the experimental groups A and B did not differ significantly (p > 0.05) from that of the rams in the control group. However, the mean values of semen gross motility (p < 0.0001) (16.50 ± 4.00% and 37.50 ± 4.30% for groups A and B, respectively at week 14 vs 90.9 ± 6.37% for group C at week 14). Percent live spermatozoa also differed significantly (p < 0.05) (66.4 ± 4.99% at week 14 for group A and B vs 83.2 ± 2.06% at week 14 for the control group). The sperm cell abnormalities were significantly higher (p < 0.001) in the treatment groups (37.3 ±1.31% and 46.8 ± 1.62 for group A and B, respectively) than in the control group (19.2 ± 1.32%). We conclude that dietary gossypol from whole cottonseed and cottonseed cake fed at 48% of the diet to Yankasa rams significantly altered their semen quality of Yankasa rams. We recommend that these cotton products should be minimised in feeds for rams intended for breeding purposes.

Limited options are available for treating patients with advanced prostate cancer (PC). Melanoma differentiation associated gene-7/interleukin-24 ( mda -7/IL-24), an IL-10 family cytokine, exhibits pleiotropic anticancer activities without adversely affecting normal cells. We previously demonstrated that suppression of the prosurvival Bcl-2 family member, myeloid cell leukemia-1 (Mcl-1), is required for mda -7/IL-24–mediated apoptosis of prostate carcinomas. Here we demonstrate that pharmacological inhibition of Mcl-1 expression with the unique Apogossypol derivative BI-97C1, also called Sabutoclax, is sufficient to sensitize prostate tumors to mda -7/IL-24–induced apoptosis, whereas ABT-737, which lacks efficacy in inhibiting Mcl-1, does not sensitize mda -7/IL-24–mediated cytotoxicity. A combination regimen of tropism-modified adenovirus delivered mda -7/IL-24 (Ad.5/3- mda -7) and BI-97C1 enhances cytotoxicity in human PC cells, including those resistant to mda -7/IL-24 or BI-97C1...

Structure-based modeling combined with rational drug design, and high throughput screening approaches offer significant potential for identifying and developing lead compounds with therapeutic potential. The present review focuses on these two approaches using explicit examples based on specific derivatives of Gossypol generated through rational design and applications of a cancer-specificpromoter derived from Progression Elevated Gene-3. The Gossypol derivative Sabutoclax (BI-97C1) displays potent anti-tumor activity against a diverse spectrum of human tumors. The model of the docked structure of Gossypol bound to Bcl-XL provided a virtual structure-activity-relationship where appropriate modifications were predicted on a rational basis. These structure-based studies led to the isolation of Sabutoclax, an optically pure isomer of Apogossypol displaying superior efficacy and reduced toxicity. These studies illustrate the power of combining structure-based modeling with rational desi...

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. Fertility was significantly reduced in male rats treated with gossypol in that a significant decrease in epididymal sperm count was observed (P &lt; 0.05) and the number of offspring was significantly reduced in females mated with them (P &lt; 0.05). This dysfunction was prevented by vitamin E. Gossypol caused a significant increase in the activity of the enzymes glutathione peroxidase (P &lt; 0.01) and glutathione reductase (P &lt; 0.01), but ...