Preventive Effects of Bee Venom Derived Phospholipase A2 on Oxaliplatin-Induced Neuropathic Pain in Mice

Li, Dongxing; Kim, Woojin; Shin, Dasom; Jung, Yong-Jae; Bae, Hyunsu; Kim, Sun Kwang

doi:10.3390/toxins8010027

Cited by 33 publications

(41 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with these data, type IIA PLA 2 has been localized by immunohistochemistry to the spinal trigeminal and facial motor nuclei and dorsal- and ventral-horns of the spinal cord [36], implying an important role of CNS sPLA 2 in nociceptive transmission. It has also been shown that the treatment of mice with bee venom PLA 2 might prevent oxaliplatin-induced neuropathic pain [37]. Given our data shows an interaction of PP PLA 2 with α9α10 nAChR, we suggest that the PLA 2 interaction with this receptor may be involved in the pain transmission pathway.…”

Section: Discussionsupporting

confidence: 58%

Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors

et al. 2017

View full text Add to dashboard Cite

Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which can be explained by phospholipid hydrolysis, and each enzyme has a specific effect. We have earlier demonstrated the capability of several snake venom PLA2s with different enzymatic, cytotoxic, anticoagulant and antiproliferative properties, to decrease acetylcholine-induced currents in Lymnaea stagnalis neurons, and to compete with α-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs) and acetylcholine binding protein. Since nAChRs are implicated in postsynaptic and presynaptic activities, in this work we probe those PLA2s known to have strong presynaptic effects, namely β-bungarotoxin from Bungarus multicinctus and crotoxin from Crotalus durissus terrificus. We also wished to explore whether mammalian PLA2s interact with nAChRs, and have examined non-toxic PLA2 from porcine pancreas. It was found that porcine pancreatic PLA2 and presynaptic β-bungarotoxin blocked currents mediated by nAChRs in Lymnaea neurons with IC50s of 2.5 and 4.8 μM, respectively. Crotoxin competed with radioactive α-bungarotoxin for binding to Torpedo and human α7 nAChRs and to the acetylcholine binding protein. Pancreatic PLA2 interacted similarly with these targets; moreover, it inhibited radioactive α-bungarotoxin binding to the water-soluble extracellular domain of human α9 nAChR, and blocked acetylcholine induced currents in human α9α10 nAChRs heterologously expressed in Xenopus oocytes. These and our earlier results show that all snake PLA2s, including presynaptically active crotoxin and β-bungarotoxin, as well as mammalian pancreatic PLA2, interact with nAChRs. The data obtained suggest that this interaction may be a general property of all PLA2s, which should be proved by further experiments.

show abstract

Section: Discussionsupporting

confidence: 58%

Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Several studies have demonstrated that boosting the Treg subpopulation through the intrathecal adoptive transfer of Tregs or the administration of the Treg-enhancing bee venom-derived phospholipase A 2 reduces chemotherapy-induced neuropathic pain in rodents. 104,106 With respect to regulatory cytokines, oxaliplatin-induced mechanohypersensitivity is associated with reduced levels of the anti-inflammatory cytokines IL-10 and IL-4 in the spinal dorsal horn. 107 Conversely, intrathecal IL-10 gene therapy or the intrathecal administration of recombinant IL-10 has been shown to progressively reverse the allodynic state associated with paclitaxel treatment.…”

Section: Contribution Of Nitro-oxidative Stress To Cipnmentioning

confidence: 99%

“…In this regard, boosting the endogenous anti‐inflammatory state might serve as another route to pain resolution in patients with CIPN. Several studies have demonstrated that boosting the Treg subpopulation through the intrathecal adoptive transfer of Tregs or the administration of the Treg‐enhancing bee venom‐derived phospholipase A 2 reduces chemotherapy‐induced neuropathic pain in rodents . With respect to regulatory cytokines, oxaliplatin‐induced mechanohypersensitivity is associated with reduced levels of the anti‐inflammatory cytokines IL‐10 and IL‐4 in the spinal dorsal horn .…”

Section: Introductionmentioning

confidence: 99%

Beyond symptomatic relief for chemotherapy‐induced peripheral neuropathy: Targeting the source

Kavelaars

Dougherty

et al. 2018

Cancer

123

111

View full text Add to dashboard Cite

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse side effect of many chemotherapeutic agents, affecting >60% of patients with cancer. Moreover, CIPN persists long into survivorship in approximately 20% to 30% of these patients. To the authors' knowledge, no drugs have been approved to date by the US Food and Drug Administration to effectively manage chemotherapy-induced neuropathic pain. The majority of the drugs tested for the management of CIPN aim at symptom relief, including pain and paresthesia, yet are not very efficacious. The authors propose that there is a need to acquire a more thorough understanding of the etiology of CIPN so that effective, mechanism-based, disease-modifying interventions can be developed. It is important to note that such interventions should not interfere with the antitumor effects of chemotherapy. Mitochondria are rod-shaped cellular organelles that represent the powerhouses of the cell, in that they convert oxygen and nutrients into the cellular energy "currency" adenosine triphosphate. In addition, mitochondria regulate cell death. Neuronal mitochondrial dysfunction and the associated nitro-oxidative stress represent crucial final common pathways of CIPN. Herein, the authors discuss the potential to prevent or reverse CIPN by protecting mitochondria and/or inhibiting nitro-oxidative stress with novel potential drugs, including the mitochondrial protectant pifithrin-μ, histone deacetylase 6 inhibitors, metformin, antioxidants, peroxynitrite decomposition catalysts, and anti-inflammatory mediators including interleukin 10. This review hopefully will contribute toward bridging the gap between preclinical research and the development of realistic novel therapeutic strategies to prevent or reverse the devastating neurotoxic effects of chemotherapy on the (peripheral) nervous system. Cancer 2018;124:2289-98. © 2018 American Cancer Society.

show abstract

“…In addition to the whole venom, some phospholipases A 2 isolated from the venom have been studied as analgesics. Li et al (2015) [ 99 ] demonstrated the analgesic effect of a bee venom-derived phospholipase A 2 (bvPLA 2 ) in a model of neuropathic pain. In this study, neuropathic pain was induced in mice, by a single infusion of oxaliplatin, a compound that is widely used to treat metastatic colorectal cancer.…”

Section: Antinociception Induced By Other Animal Venoms Spla mentioning

confidence: 99%

Secreted Phospholipases A2 from Animal Venoms in Pain and Analgesia

Zambelli

Picolo

Fernandes

et al. 2017

Toxins

View full text Add to dashboard Cite

Animal venoms comprise a complex mixture of components that affect several biological systems. Based on the high selectivity for their molecular targets, these components are also a rich source of potential therapeutic agents. Among the main components of animal venoms are the secreted phospholipases A2 (sPLA2s). These PLA2 belong to distinct PLA2s groups. For example, snake venom sPLA2s from Elapidae and Viperidae families, the most important families when considering envenomation, belong, respectively, to the IA and IIA/IIB groups, whereas bee venom PLA2 belongs to group III of sPLA2s. It is well known that PLA2, due to its hydrolytic activity on phospholipids, takes part in many pathophysiological processes, including inflammation and pain. Therefore, secreted PLA2s obtained from animal venoms have been widely used as tools to (a) modulate inflammation and pain, uncovering molecular targets that are implicated in the control of inflammatory (including painful) and neurodegenerative diseases; (b) shed light on the pathophysiology of inflammation and pain observed in human envenomation by poisonous animals; and, (c) characterize molecular mechanisms involved in inflammatory diseases. The present review summarizes the knowledge on the nociceptive and antinociceptive actions of sPLA2s from animal venoms, particularly snake venoms.

show abstract

Preventive Effects of Bee Venom Derived Phospholipase A2 on Oxaliplatin-Induced Neuropathic Pain in Mice

Cited by 33 publications

References 53 publications

Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors

Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors

Beyond symptomatic relief for chemotherapy‐induced peripheral neuropathy: Targeting the source

Secreted Phospholipases A2 from Animal Venoms in Pain and Analgesia

Contact Info

Product

Resources

About