The effect of gossypol on fast axonal transport and microtubule assembly

Kanje, Martin; Ekström, Per; Deinum, Johanna; Wallin, Margareta

doi:10.1016/0005-2736(86)90134-3

Cited by 12 publications

(4 citation statements)

References 30 publications

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“…Gossypol is a phenolic compound and a male antifertility agent that occurs naturally in certain species of cotton plants of the family Malvaciae. The suggested mechanism behind the cytotoxic effect of gossypol is the inhibition of cellular energy metabolism by being a strong mitochondrial respiratory toxin and may block the microtubule assembly in sciatic nerves at μM concentrations [41]. In the present study, we show that gossypol is neuroprotective at nM concentrations.…”

Section: Discussionsupporting

confidence: 62%

Enhanced Neuronal Survival and Neurite Outgrowth Triggered by Novel Small Organic Compounds Mimicking the LewisX Glycan

et al. 2018

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Glycosylation fine-tunes signal transduction of adhesion molecules during neural development and supports synaptic plasticity and repair after injury in the adult nervous system. One abundantly expressed neural glycan is LewisX (LeX). Although it is known that its expression starts at the formation of the neural tube during the second embryonic week in the mouse and peaks during the first postnatal week, its functional relevance is only rudimentarily understood. To gain better insights into the functions of this glycan, we identified small organic compounds that mimic structurally and functionally this glycan glycosidically linked to several neural adhesion molecules. Mimetic compounds were identified by competitive enzyme-linked immunosorbent assay (ELISA) using the LeX-specific monoclonal antibodies L5 and SSEA-1 for screening a library of small organic molecules. In this assay, antibody binding to substrate-coated LeX glycomimetic peptide is measured in the presence of compounds, allowing identification of molecules that inhibit antibody binding and thereby mimic LeX. Gossypol, orlistat, ursolic acid, folic acid, and tosufloxacin inhibited antibody binding in a concentration-dependent manner. With the aim to functionally characterize the molecular consequences of the compounds' actions, we here present evidence that, at nM concentrations, the mimetic compounds enhance neurite outgrowth and promote neuronal survival of cultured mouse cerebellar granule cells via, notably, distinct signal transduction pathways. These findings raise hopes that these LeX mimetics will be powerful tools for further studying the functions of LeX and its effects in acute and chronic nervous system disease models. It is worth mentioning in this context that the LeX compounds investigated in the present study have been clinically approved for different therapies.

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Section: Discussionsupporting

confidence: 62%

Enhanced Neuronal Survival and Neurite Outgrowth Triggered by Novel Small Organic Compounds Mimicking the LewisX Glycan

et al. 2018

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“…Furthermore, it induces oxidative stress viewed as an imbalance between antioxidants and pro-oxidants, which results in the accumulation of reactive oxygen species (Kovacic, 2003;Keshmiri-Neghab and Goliaei, 2014;Santana et al, 2015). It has been reported that gossypol inhibits fast axonal transport and accumulates in the nerve, raising concerns about its possible neurotoxicity (Kanje et al, 1986). Therefore, the risk of gossypol toxicity has aroused worldwide attention due to the consumption of agricultural by-products such as cottonseed oil, milk, and meat from the affected animals.…”

Section: Introductionmentioning

confidence: 99%

Prenatal Exposure to Gossypol Impairs Corticogenesis of Mouse

Zhu

et al. 2020

Front. Neurosci.

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Gossypol is a yellow polyphenolic compounds extracted from roots, stems and seeds of cotton plants. Excessive intake of gossypol induces severe pathological signs of toxicity in livestock and wildlife. Currently, gossypol has received widespread attention for its toxic effects on the reproductive system. However, reports of the effects of gossypol during corticogenesis and the development of the mouse cerebral cortex are unavailable. In the present study, gossypol was orally administrated at a dose of 0, 20, and 50 mg/kg body weight/day to pregnant mice from embryonic day 6.5 to the time of sample collection. We used in utero electroporation and immunofluorescence to demonstrate that gossypol impaired cortical neuronal migration. Furthermore, labeling with 5-bromo-2-deoxyuridine and western blot analysis revealed that gossypol disturbed the balance between proliferation and differentiation of neural progenitors, inhibited neural progenitor cell proliferation, neuronal differentiation, and maturation. Additionally, cortical progenitor apoptotic cell death increased in the developing gossypol-treated cortex, which was associated with NF-κB and MAPK pathways. In conclusion, our findings indicate that gossypol exposure disrupted neurogenesis in the developing neocortex, suggesting the potentially harmful impact of gossypol on the cerebral cortex development of humans and livestock.

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“…It accumulated in the nerve and the results indicate that may act as a potent neurotoxin (Kanje et al, 1986). Gossypol causes oxidative stress, it interact directly with biological membranes and promote formation of highly reactive oxygen containing free radicals.…”

Section: Introductionmentioning

confidence: 99%

The developmental toxicity of cottonseed extraction on chicken embryo

Sadighara¹,

Amoli²,

Ashrafihelan³

et al. 2011

Rev. bras. farmacogn.

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Cottonseed meal is widely used as one of the protein supplement in poultry diets. Its mechanism of toxic action on chicken embryo is poorly understood. In this study, direct effects and abnormalities of cottonseed on chicken embryo were studied. Oxidative stress, cholinergic stress, mineral analysis and microscopic lesions were analyzed in chicken embryo which injected cottonseed extraction in 0.1, 1 and 10 mg concentration (with free gossypol 0.25 ppm, 2.5 ppm and 25 ppm respectively) at day 4 of incubation. Higher group had 100% mortality. Serum of alive chicken embryo at day 20 of incubation were measured for FRAP (ferric reducing ability of serum), total SH groups assay, cholinesterase assay and potassium concentration. The results expressed as mean±SD show to increase oxidative stress, cholinergic stress but significant difference (p≤0.05) wasn't observed between groups. The significant difference was observed in potassium concentration in serum. Some evidence of hematotoxicity such as hemorrhage and higher number of puntate reticulocytes were detected. It is concluded, hematoxicity and hyperkalemia are toxicity mechanisms that could initiate in low concentrations of cottonseed in chick embryo.

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The effect of gossypol on fast axonal transport and microtubule assembly

Cited by 12 publications

References 30 publications

Enhanced Neuronal Survival and Neurite Outgrowth Triggered by Novel Small Organic Compounds Mimicking the LewisX Glycan

Enhanced Neuronal Survival and Neurite Outgrowth Triggered by Novel Small Organic Compounds Mimicking the LewisX Glycan

Prenatal Exposure to Gossypol Impairs Corticogenesis of Mouse

The developmental toxicity of cottonseed extraction on chicken embryo

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