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Theriogenology Apr 2018The aim of the present study was to analyze seminal quality of young bulls subjected to different frequencies of gossypol supplementation. Forty-eight Nellore bulls,... (Randomized Controlled Trial)
Randomized Controlled Trial
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 ± 7.2 kg, were used in this study. Animals were fed with 10.5 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 (P = .009) and head (P = .005) defects in comparison to animals receiving only forage and mineral supplement. Infrequent supplementation, particularly 5 times in the week (G5X), increased head (P = .026) and midpiece (P = .014) abnormalities. Sperm motility in fresh semen was lower in animals that received daily supplementation than those supplemented on alternate days (P = .021). Additionally, animals supplemented daily showed lower percentage of spermatozoa with intact acrosome compared to those supplemented on alternate days (P = .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.
Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Cattle; Cryopreservation; Dietary Supplements; Dose-Response Relationship, Drug; Drug Administration Schedule; Gossypol; Male; Reproduction; Semen; Semen Analysis; Semen Preservation; Sexual Maturation; Spermatogenesis
PubMed: 29407896
DOI: 10.1016/j.theriogenology.2018.01.003 -
Science China. Life Sciences Feb 2016Sesquiterpenoids are a class of 15-carbon secondary metabolites that play diverse roles in plant adaptation to environment. Cotton plants accumulate a large amount of... (Review)
Review
Sesquiterpenoids are a class of 15-carbon secondary metabolites that play diverse roles in plant adaptation to environment. Cotton plants accumulate a large amount of sesquiterpene aldehydes (including gossypol) as phytoalexins against pathogens and herbivores. They are stored in pigment glands of aerial organs and in epidermal layers of roots. Several enzymes of gossypol biosynthesis pathway have been characterized, including 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) and farnesyl diphosphate synthase (FPS) that catalyze the formation of the precursor farnesyl diphosphate (FPP), (+)-δ-cadinene synthase (CDN) which is the first enzyme committed to gossypol biosynthesis, and the downstream enzymes of CYP706B1 and methyltransferase. Expressions of these genes are tightly regulated during cotton plants development and induced by jasmonate and fungi elicitors. The transcription factor GaWRKY1 has been shown to be involved in gossypol pathway regulation. Recent development of new genomic platforms and methods and releases of diploid and tetraploid cotton genome sequences will greatly facilitate the elucidation of gossypol biosynthetic pathway and its regulation.
Topics: Gossypium; Gossypol; Hydroxymethylglutaryl CoA Reductases; Sesquiterpenes; Phytoalexins
PubMed: 26803304
DOI: 10.1007/s11427-016-5003-z -
Frontiers in Nutrition 2022Microbial fermentation is an effective method to degrade free-gossypol, which is a toxic substance restricting the utilization of cottonseed meal in animal husbandry....
Microbial fermentation is an effective method to degrade free-gossypol, which is a toxic substance restricting the utilization of cottonseed meal in animal husbandry. However, there are few researches on the nutritional effect and the change of bacterial community on cottonseed meal fermented with anaerobic solid-state fermentation. This study evaluated the effects of fermentation with sp. on gossypol degradation and nutritional quality improvement in cottonseed meal (CM), as well as the changes of bacterial community structure during fermentation. The strains with high activity for digesting free gossypol were screened from high protease-producing strains preserved in the laboratory. Then the strains which had both the gossypol degradation activity and protease producing activity were selected to degrade macromolecular protein and free gossypol in CM. The unsterilized SSF medium was inoculated with 10 CFU/kg culture and fermented at room temperature for 14 days. Each group had three parallels. And the effects of anaerobic solid-state fermentation on unsterilized CM was evaluated. Results showed that for the seven strains with high activity for digesting free gossypol and producing protease that were screened, free gossypol content in fermented cottonseed meal (FCM) decreased and acid-soluble protein (ASP) contents increased. Among them, strain M-15 had the best fermentation effect, with the free gossypol degradation rate of 93.46% and acid soluble protein content of 13.26%. M-15 was identified as . During fermentation with M-15, the bacterial diversity in CM was reduced, but not significant and the community structure was simpler significantly. The strain M-15 selected in this experiment reduced the free gossypol content and improved the nutritional quality of CM through anaerobic solid-state fermentation, which can be used for industrial large-scale production.
PubMed: 36570163
DOI: 10.3389/fnut.2022.1017637 -
Toxins Nov 2022Gossypol is a polyphenolic toxic secondary metabolite derived from cotton. Free gossypol in cotton meal is remarkably harmful to animals. Furthermore, microbial...
Gossypol is a polyphenolic toxic secondary metabolite derived from cotton. Free gossypol in cotton meal is remarkably harmful to animals. Furthermore, microbial degradation of gossypol produces metabolites that reduce feed quality. We adopted an enzymatic method to degrade free gossypol safely and effectively. We cloned the gene encoding carboxylesterase (CarE) into pPICZαA and transformed it into GS115. The target protein was successfully obtained, and CarE could effectively degrade free gossypol with a degradation rate of 89%. When esterase was added, the exposed toxic groups of gossypol reacted with different amino acids and amines to form bound gossypol, generating substances with (M + H) / ratios of 560.15, 600.25, and 713.46. The molecular formula was CHO, CHNO, and CHNO. The observed instability of the hydroxyl groups caused the substitution and shedding of the group, forming a substance with / of 488.26 and molecular formula CHO. These properties render the CarE a valid candidate for the detoxification of cotton meal. Furthermore, the findings help elucidate the degradation process of gossypol in vitro.
Topics: Animals; Carboxylesterase; Gossypol; Moths; Pichia; Biotransformation; Recombinant Proteins
PubMed: 36548713
DOI: 10.3390/toxins14120816 -
Pharmaceuticals (Basel, Switzerland) Jan 2022The potential of gossypol and of its R-(-)-enantiomer (R-(-)-gossypol acetic acid, AT-101), has been evaluated for treatment of cancer as an independent agent and in... (Review)
Review
The potential of gossypol and of its R-(-)-enantiomer (R-(-)-gossypol acetic acid, AT-101), has been evaluated for treatment of cancer as an independent agent and in combination with standard chemo-radiation-therapies, respectively. This review assesses the evidence for safety and clinical effectiveness of oral gossypol/AT-101 in treating various types of cancer. The databases PubMed, MEDLINE, Cochrane, and ClinicalTrials.gov were examined. Phase I and II trials as well as single arm and randomized trials were included in this review. Results were screened to determine if they met inclusion criteria and then summarized using a narrative approach. A total of 17 trials involving 759 patients met the inclusion criteria. Overall, orally applied gossypol/AT-101 at low doses (30 mg daily or lower) was determined as well tolerable either as monotherapy or in combination with chemo-radiation. Adverse events should be strictly monitored and were successfully managed by dose-reduction or treating symptoms. There are four randomized trials, two performed in patients with advanced non-small cell lung cancer, one in subjects with head and neck cancer, and one in patients with metastatic castration-resistant prostate cancer. Thereby, standard chemotherapy (either docetaxel (two trials) or docetaxel plus cisplatin or docetaxel plus prednisone) was tested with and without AT-101. Within these trials, a potential benefit was observed in high-risk patients or in some patients with prolongation in progression-free survival or in overall survival. Strikingly, the most recent clinical trial combined low dose AT-101 with docetaxel, fluorouracil, and radiation, achieving complete responses in 11 of 13 patients with gastroesophageal carcinoma (median duration of 12 months) and a median progression-free survival of 52 months. The promising results shown in subsets of patients supports the need of further specification of AT-101 sensitive cancers as well as for the establishment of effective AT-101-based therapy. In addition, the lowest recommended dose of gossypol and its precise toxicity profile need to be confirmed in further studies. Randomized placebo-controlled trials should be performed to validate these data in large cohorts.
PubMed: 35215257
DOI: 10.3390/ph15020144 -
International Journal of Molecular... Apr 2022Cotton refers to species in the genus that bear spinnable seed coat fibers. A total of 50 species in the genus have been described to date. Of these, only four... (Review)
Review
Cotton refers to species in the genus that bear spinnable seed coat fibers. A total of 50 species in the genus have been described to date. Of these, only four species, viz. , and are cultivated; the rest are wild. The black dot-like structures on the surfaces of cotton organs or tissues, such as the leaves, stem, calyx, bracts, and boll surface, are called gossypol glands or pigment glands, which store terpenoid aldehydes, including gossypol. The cotton () pigment gland is a distinctive structure that stores gossypol and its derivatives. It provides an ideal system for studying cell differentiation and organogenesis. However, only a few genes involved in the process of gland formation have been identified to date, and the molecular mechanisms underlying gland initiation remain unclear. The terpenoid aldehydes in the lysigenous glands of species are important secondary phytoalexins (with gossypol being the most important) and one of the main defenses of plants against pests and diseases. Here, we review recent research on the development of gossypol glands in species, the regulation of the terpenoid aldehyde biosynthesis pathway, discoveries from genetic engineering studies, and future research directions.
Topics: Aldehydes; Cotton Fiber; Gene Expression Regulation, Plant; Gossypium; Gossypol; Organogenesis; Terpenes
PubMed: 35563290
DOI: 10.3390/ijms23094892 -
Advanced Science (Weinheim,... Dec 2022Outbreaks of coronaviruses (CoVs), especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have posed serious threats to humans and animals, which...
Outbreaks of coronaviruses (CoVs), especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have posed serious threats to humans and animals, which urgently calls for effective broad-spectrum antivirals. RNA-dependent RNA polymerase (RdRp) plays an essential role in viral RNA synthesis and is an ideal pan-coronaviral therapeutic target. Herein, based on cryo-electron microscopy and biochemical approaches, gossypol (GOS) is identified from 881 natural products to directly block SARS-CoV-2 RdRp, thus inhibiting SARS-CoV-2 replication in both cellular and mouse infection models. GOS also acts as a potent inhibitor against the SARS-CoV-2 variant of concern (VOC) and exerts same inhibitory effects toward mutated RdRps of VOCs as the RdRp of the original SARS-CoV-2. Moreover, that the RdRp inhibitor GOS has broad-spectrum anti-coronavirus activity against alphacoronaviruses (porcine epidemic diarrhea virus and swine acute diarrhea syndrome coronavirus), betacoronaviruses (SARS-CoV-2), gammacoronaviruses (avian infectious bronchitis virus), and deltacoronaviruses (porcine deltacoronavirus) is showed. The findings demonstrate that GOS may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and other coronavirus outbreaks.
Topics: Animals; Humans; Mice; COVID-19; Cryoelectron Microscopy; Gossypol; Pandemics; SARS-CoV-2; Swine; COVID-19 Drug Treatment; Coronavirus Infections; Coronavirus RNA-Dependent RNA Polymerase
PubMed: 36266926
DOI: 10.1002/advs.202203499 -
A gossypol derivative effectively protects against Zika and dengue virus infection without toxicity.BMC Biology Jun 2022Zika virus (ZIKV) and dengue virus (DENV) cause microcephaly and dengue hemorrhagic fever, respectively, leading to severe problems. No effective antiviral agents are...
BACKGROUND
Zika virus (ZIKV) and dengue virus (DENV) cause microcephaly and dengue hemorrhagic fever, respectively, leading to severe problems. No effective antiviral agents are approved against infections of these flaviviruses, calling for the need to develop potent therapeutics. We previously identified gossypol as an effective inhibitor against ZIKV and DENV infections, but this compound is toxic and not suitable for in vivo treatment.
RESULTS
In this study, we showed that gossypol derivative ST087010 exhibited potent and broad-spectrum in vitro inhibitory activity against infections of at least ten ZIKV strains isolated from different hosts, time periods, and countries, as well as DENV-1-4 serotypes, and significantly reduced cytotoxicity compared to gossypol. It presented broad-spectrum in vivo protective efficacy, protecting ZIKV-infected Ifnar1 mice from lethal challenge, with increased survival and reduced weight loss. Ifnar1 mice treated with this gossypol derivative decreased viral titers in various tissues, including the brain and testis, after infection with ZIKV at different human isolates. Moreover, ST087010 potently blocked ZIKV vertical transmission in pregnant Ifnar1 mice, preventing ZIKV-caused fetal death, and it was safe for pregnant mice and their pups. It also protected DENV-2-challenged Ifnar1 mice against viral replication by reducing the viral titers in the brain, kidney, heart, and sera.
CONCLUSIONS
Overall, our data indicate the potential for further development of this gossypol derivative as an effective and safe broad-spectrum therapeutic agent to treat ZIKV and DENV diseases.
Topics: Animals; Cross Reactions; Dengue; Dengue Virus; Female; Gossypol; Male; Mice; Pregnancy; Zika Virus; Zika Virus Infection
PubMed: 35706035
DOI: 10.1186/s12915-022-01344-w -
Animal Nutrition (Zhongguo Xu Mu Shou... Dec 2021Gossypol, a phenolic compound found in the cotton plant, is widely distributed in cottonseed by-products. Although ruminant animals are believed to be more tolerant of... (Review)
Review
Gossypol, a phenolic compound found in the cotton plant, is widely distributed in cottonseed by-products. Although ruminant animals are believed to be more tolerant of gossypol toxicity than monogastric animals due to rumen microbial fermentation, the actual mechanisms of detoxification remain unclear. In contrast, the metabolic detoxification of gossypol by (Lepidoptera: Noctuidae) larvae has achieved great advances. The present review discusses the clinical signs of gossypol in ruminant animals, as well as summarizing advances in the study of gossypol detoxification in the rumen. It also examines the regulatory roles of several key enzymes in gossypol detoxification and transformation known in . With the rapid development of modern molecular biotechnology and -omics technology strategies, evidence increasingly indicates that research into the biological degradation of gossypol in larvae and some microbes, in terms of these key enzymes, could provide scientific insights that would underpin future work on microbial gossypol detoxification in the rumen, with the ultimate aim of further alleviating gossypol toxicity in ruminant animals.
PubMed: 34703914
DOI: 10.1016/j.aninu.2021.02.007