Cisplatin-induced alterations in the blood-nerve barrier: effects of combination of vitamin B1, B6 and B12

Tothonglor, Amornrat; Kobutree, Phetnarin; Roumwong, Atitaya; Jindatip, Depicha; Agthong, Sithiporn

doi:10.5603/fm.a2022.0008

Cited by 4 publications

(3 citation statements)

References 16 publications

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“…This produced a retention of food that led to stomach enlargement. It is known that peripheral nervous failure (dysautonomia) can be produced by toxic molecules, in this case, by cisplatin [ 51 ].…”

Section: Resultsmentioning

confidence: 99%

Exosomes loaded with ultrasmall Pt nanoparticles: a novel low-toxicity alternative to cisplatin

et al. 2022

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Background Platinum nanoparticles have been demonstrated to have excellent anticancer properties. However, because of the lack of specificity they must be delivered to the tumor in amounts sufficient to reach the desired therapeutic objectives. Interestingly, exosomes are considered as excellent natural selective delivery nanotools, but until know their targeting properties have not being combined with the anticancer properties of platinum nanoparticles. Results In this work we combine the targeting capabilities of exosomes and the antitumoral properties of ultrasmall (< 2 nm) platinum nanoparticles as a novel, low toxicity alternative to the use of cisplatin. A mild methodology based on the room temperature CO-assisted in situ reduction of Pt2+ precursor was employed to preserve the integrity of exosomes, while generating ultrasmall therapeutic PtNPs directly inside the vesicles. The resulting PtNPs-loaded exosomes constitute a novel hybrid bioartificial system that was readily internalized by the target cells inducing antiproliferative response, as shown by flow cytometry and microscopy experiments in vitro. In vivo Pt-Exos showed antitumoral properties similar to that of cisplatin but with a strongly reduced or in some cases no toxic effect, highlighting the advantages of this approach and its potential for translation to the clinic. Conclusions In this study, a nanoscale vector based on ultrasmall PtNPs and exosomes has been created exhibiting antitumoral properties comparable or higher to those of the FDA approved cisplatin. The preferential uptake of PtNPs mediated by exosomal transfer between certain cell types has been exploited to create a selective antitumoral novel bioartificial system. We have demonstrated their anticancer properties both in vitro and in vivo comparing the results obtained with the administration of equivalent amounts of cisplatin, and showing a spectacular reduction of toxicity.

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Section: Resultsmentioning

confidence: 99%

Exosomes loaded with ultrasmall Pt nanoparticles: a novel low-toxicity alternative to cisplatin

et al. 2022

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“…However, the pericytes seemed to have a normal appearance. In comparison, Tothonglor et al 47 reported that cisplatin affected BNB via the separation of pericytes from the thicker BM. When S1P binds with the S1P receptor 2, there might be cross‐talk with vascular endothelial growth factor to stimulate inflammation 18,19 .…”

Section: Discussionmentioning

confidence: 96%

Differences in the ultrastructure of neurons in the spinal ganglion and dorsal rootlet between rats treated with cisplatin only versus co‐administration with a sphingosine 1‐phosphate receptor 2 agonist in attenuating neuropathy and allodynia

Chayaburakul

Ong

Herr

et al. 2023

J Peripheral Nervous Sys

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Background and AimsCisplatin is a chemotherapeutic agent for many types of cancer. The neurotoxicity of cisplatin includes neuropathy and allodynia. We aimed to study structural changes by using CYM54‐78, attenuating cisplatin‐induced neuropathy and blocking the pathogenesis in neurons, and promoting axonal regeneration.MethodsTEM (transmission electron microscopy) was used to distinguish ultrastructural changes in dorsal root ganglion (DRG) and dorsal rootlets (DR) between rats treated with cisplatin alone and rats co‐treated with cisplatin and sphingosine ‐1‐phosphate receptor2 (S1P2) agonist, CYM‐5478.ResultsIn DRG of rats treated with cisplatin alone, TEM micrographs showed necrosis and apoptotic cells. Neuronal cytoplasm showed numerous vacuole (stage C) and swelling (stage B➔C) mitochondrial degeneration. Neurons in DRG from cisplatin+CYM‐5478 group showed a higher percentage of healthy mitochondria (from 5.3% to 75.6%) than those treated with cisplatin alone. DR of cisplatin only group showed abnormal axoplasm, axolemma, and focal detached myelin sheaths, especially in Aδ (fast pain) and Aβ (touch) fibers, and revealed collateral branches that sprouted from Aβ fibers, which is characteristic of allodynia. Moreover, vasoconstriction was observed in DRG and DR. Rats in cisplatin+CYM‐5478 group showed not only fewer abnormal structures than those in cisplatin only group, but also showed Bands of Büngner and onion bulb‐like structures, which are characteristic of nerve regeneration.InterpretationTogether with our previous study, showed that CYM‐5478 attenuated neuropathy and allodynia in a rat model of cisplatin‐induced neuropathy, these results suggest S1P2 agonists as a potential approach the for treatment of cancer due to the reduction of side effects of cisplatin.

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“…Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxicities. Combination of vitamins (B1 : B6 : B12 ¼ 100 : 100 : 1) was demonstrated to reduce CIPN by inhibiting the toxic effects [22]. Combination of these vitamins may play more important roles in supporting the activity of a suffering nerve and in the therapeutic management of neuropathies [23,24].…”

Section: Combination Of B Vitaminsmentioning

confidence: 99%

Vitamins in neuropathy: pathophysiological and therapeutic roles

Chen,

Song

2023

Current Opinion in Neurology

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Purpose of review Vitamin deficiency is a risk factor in the development of peripheral neuropathy, which leads to complex and severe diseases. This review provides an update overview of the literature on the roles of vitamins in peripheral neuropathy, highlighting their pathophysiological and therapeutic roles. Recent findings The importance and clinical manifestations and implications of the vitamins and vitamin deficiencies are further demonstrated in peripheral neuropathy and the associated diseases. Vitamin deficiency is common in various severe and complex diseases such as diabetes, chemotherapy, acute nutritional axonal neuropathy, dermatitis, complex regional pain syndrome, postherpetic neuralgia, carpal tunnel syndrome, and so forth and some rare clinical case reports. There is evidence that deficiencies of almost all vitamins are associated with diabetic neuropathy. Vitamin supplementation may serve as an effective therapeutic strategy. Summary The vitamins play critical roles in maintaining physiological functions, and vitamin deficiencies cause peripheral neuropathy with various severe and complex diseases. The therapeutic benefits of vitamins and further understanding of the mechanisms for vitamin treatment effects should be emphasized and highlighted. More clinical trials are needed to establish optimal treatment strategies for vitamins in the various neuropathies. A large range of people/patients screening for vitamin deficiencies may be considered in order to provide early diagnosis and timely medical assistance.

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Cisplatin-induced alterations in the blood-nerve barrier: effects of combination of vitamin B1, B6 and B12

Abstract: This article has been peer reviewed and published immediately upon acceptance.It is an open access article, which means that it can be downloaded, printed, and distributed freely, provided the work is properly cited. Articles in "Folia Morphologica" are listed in PubMed.

Cited by 4 publications

References 16 publications

Exosomes loaded with ultrasmall Pt nanoparticles: a novel low-toxicity alternative to cisplatin

Exosomes loaded with ultrasmall Pt nanoparticles: a novel low-toxicity alternative to cisplatin

Differences in the ultrastructure of neurons in the spinal ganglion and dorsal rootlet between rats treated with cisplatin only versus co‐administration with a sphingosine 1‐phosphate receptor 2 agonist in attenuating neuropathy and allodynia

Vitamins in neuropathy: pathophysiological and therapeutic roles

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