Melittin, a honeybee venom derived peptide for the treatment of chemotherapy-induced peripheral neuropathy

Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of cancer treatment which involves sensory and motor nerve dysfunction. Severe CIPN has been reported in around 5% of patients treated with single and up to 38% of patients treated with multiple chemotherapeutic agents. Present medications available for CIPN are the use of opioids, nonsteroidal anti-inflammatory agents, and tricyclic antidepressants, which are only marginally effective in treating neuropathic symptoms. In reality, symptom reappears after these drugs are discontinued. The pathogenesis of CIPN has not been sufficiently recognized and methods for the prevention and treatment of CIPN remain vulnerable to therapeutic problems. It has witnessed that the present medicines available for the disease offer only symptomatic relief for the short term and have severe adverse side effects. There is no standard treatment protocol for preventing, reducing, and treating CIPN. Therefore, there is a need to develop curative therapy that can be used to treat this complication. Melittin is the main pharmacological active constituent of honeybee venom and has therapeutic values including in chemotherapeutic-induced peripheral neuropathy. It has been shown that melittin and whole honey bee venom are effective in treating paclitaxel and oxaliplatin-induced peripheral neuropathy. The use of melittin against peripheral neuropathy caused by chemotherapy has been limited despite having strong therapeutic efficacy against the disease. Melittin mediated haemolysis is the key reason to restrict its use. In our study, it is found that α-Crystallin (an eye lens protein) is capable of inhibiting melittin-induced haemolysis which gives hope of using an appropriate combination of melittin and α-Crystallin in the treatment of CIPN. The review summarizes the efforts made by different research groups to address the concern with melittin in the treatment of chemotherapeutic-induced neuropathy. It also focuses on the possible approaches to overcome melittin-induced haemolysis. Graphic Abstract

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The Therapeutic Potential of Chemokines in the Treatment of Chemotherapy- Induced Peripheral Neuropathy

Current Drug Targets ◽

10.2174/1389450120666190906153652 ◽

2020 ◽

Vol 21 (3) ◽

pp. 288-301 ◽

Cited By ~ 5

Author(s):

Lin Zhou ◽

Luyao Ao ◽

Yunyi Yan ◽

Wanting Li ◽

Anqi Ye ◽

...

Keyword(s):

Nervous System ◽

Neuropathic Pain ◽

Immune System ◽

Peripheral Neuropathy ◽

Immune Cell ◽

Therapeutic Potential ◽

Chemotherapeutic Agents ◽

Cell Trafficking ◽

Mediated Communication ◽

Novel Therapeutic Strategies

Background: Some of the current challenges and complications of cancer therapy are chemotherapy- induced peripheral neuropathy (CIPN) and the neuropathic pain that are associated with this condition. Many major chemotherapeutic agents can cause neurotoxicity, significantly modulate the immune system and are always accompanied by various adverse effects. Recent evidence suggests that cross-talk occurs between the nervous system and the immune system during treatment with chemotherapeutic agents; thus, an emerging concept is that neuroinflammation is one of the major mechanisms underlying CIPN, as demonstrated by the upregulation of chemokines. Chemokines were originally identified as regulators of peripheral immune cell trafficking, and chemokines are also expressed on neurons and glial cells in the central nervous system. Objective: In this review, we collected evidence demonstrating that chemokines are potential mediators and contributors to pain signalling in CIPN. The expression of chemokines and their receptors, such as CX3CL1/CX3CR1, CCL2/CCR2, CXCL1/CXCR2, CXCL12/CXCR4 and CCL3/CCR5, is altered in the pathological conditions of CIPN, and chemokine receptor antagonists attenuate neuropathic pain behaviour. Conclusion: By understanding the mechanisms of chemokine-mediated communication, we may reveal chemokine targets that can be used as novel therapeutic strategies for the treatment of CIPN.

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Ayurvedic management of Retinitis Pigmentosa (Doshandha) - A Case Study

Journal of Ayurveda and Integrated Medical Sciences (JAIMS) ◽

10.21760/jaims.v2i05.10275 ◽

2017 ◽

Vol 2 (05) ◽

Author(s):

Anju D. ◽

Pushpa Raj Poudel ◽

Ajoy Viswam ◽

Ashwini M. J.

Keyword(s):

Retinitis Pigmentosa ◽

Low Vision ◽

Symptomatic Relief ◽

Retinal Dystrophy ◽

Treatment Protocol ◽

Signs And Symptoms ◽

Photoreceptor Cells ◽

Rod Photoreceptor ◽

Night Time ◽

Initial Symptoms

Retinitis pigmentosa (RP) is an inherited, degenerative eye disease that causes severe vision impairment due to the progressive degeneration of rod photoreceptor cells in retina. This form of retinal dystrophy manifests initial symptoms independentof age; thus, RP diagnosis occurs anywhere from early infancy to late adulthood. This primary pigmentary retinal dystrophy is a hereditary disorder predominantly affecting the rods more than the cones. The main classical triads of retinitis pigmentosa are arteriolar attenuation, Retinal bone spicule pigmentation and Waxy disc pallor. The main treatment of retinitis pigmentosa is by using Low vision aids (LVA) and Genetic counseling. As such a complete cure for retinitis pigmentosa is not present. So a treatment protocol has to be adopted that helps in at least the symptomatic relief. In Ayurveda, the signs and symptoms of this can be compared with the Lakshanas of Doshandha which is one among the Dristigata Roga. It is considered as a diseased condition in which sunset will obliterate the Dristi Mandala and makes the person blind at night time. During morning hours the rising sunrays will disperse the accumulated Dosas from Dristi to clear vision. This disease resembles Kaphajatimira in its pathogenesis, but the night blindness is the special feature. Since the disease is purely Kaphaja, a treatment attempt is planned in Kaphara and Brimhana line. The present paper discusses a case of retinitis pigmentosa and it’s Ayurvedic Treatment.

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Correction: Association of CEP72 rs924607 TT Genotype with Vincristine-induced Peripheral Neuropathy Measured by Motor Nerve Conduction Studies

Klinische Pädiatrie ◽

10.1055/a-1313-8762 ◽

2020 ◽

Vol 232 (06) ◽

pp. e12-e12

Author(s):

Marko Kavčič ◽

Aida Zečkanović ◽

Janez Jazbec ◽

Marusa Debeljak

Keyword(s):

Peripheral Neuropathy ◽

Nerve Conduction ◽

Motor Nerve ◽

Nerve Conduction Studies ◽

Motor Nerve Conduction

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Sensory-Motor Mechanisms Increasing Falls Risk in Diabetic Peripheral Neuropathy

Medicina ◽

10.3390/medicina57050457 ◽

2021 ◽

Vol 57 (5) ◽

pp. 457

Author(s):

Neil D. Reeves ◽

Giorgio Orlando ◽

Steven J. Brown

Keyword(s):

Peripheral Neuropathy ◽

Diabetic Peripheral Neuropathy ◽

Motor Nerve ◽

Step Length ◽

Falls Prevention ◽

Motor Deficits ◽

Falls Risk ◽

Walking Gait ◽

Risk Of Falls ◽

Diabetes Patients

Diabetic peripheral neuropathy (DPN) is associated with peripheral sensory and motor nerve damage that affects up to half of diabetes patients and is an independent risk factor for falls. Clinical implications of DPN-related falls include injury, psychological distress and physical activity curtailment. This review describes how the sensory and motor deficits associated with DPN underpin biomechanical alterations to the pattern of walking (gait), which contribute to balance impairments underpinning falls. Changes to gait with diabetes occur even before the onset of measurable DPN, but changes become much more marked with DPN. Gait impairments with diabetes and DPN include alterations to walking speed, step length, step width and joint ranges of motion. These alterations also impact the rotational forces around joints known as joint moments, which are reduced as part of a natural strategy to lower the muscular demands of gait to compensate for lower strength capacities due to diabetes and DPN. Muscle weakness and atrophy are most striking in patients with DPN, but also present in non-neuropathic diabetes patients, affecting not only distal muscles of the foot and ankle, but also proximal thigh muscles. Insensate feet with DPN cause a delayed neuromuscular response immediately following foot–ground contact during gait and this is a major factor contributing to increased falls risk. Pronounced balance impairments measured in the gait laboratory are only seen in DPN patients and not non-neuropathic diabetes patients. Self-perception of unsteadiness matches gait laboratory measures and can distinguish between patients with and without DPN. Diabetic foot ulcers and their associated risk factors including insensate feet with DPN and offloading devices further increase falls risk. Falls prevention strategies based on sensory and motor mechanisms should target those most at risk of falls with DPN, with further research needed to optimise interventions.

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Herbal Medicine Goshajinkigan Prevents Paclitaxel-Induced Mechanical Allodynia without Impairing Antitumor Activity of Paclitaxel

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/849754 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 16

Author(s):

Muh. Akbar Bahar ◽

Tsugunobu Andoh ◽

Keisuke Ogura ◽

Yoshihiro Hayakawa ◽

Ikuo Saiki ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Herbal Medicine ◽

Tumor Growth ◽

Mechanical Allodynia ◽

Chemotherapeutic Agents ◽

Antitumor Action ◽

Effective Strategies ◽

Anti Cancer ◽

Mammary Fat Pad ◽

4T1 Cells

Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect of commonly used chemotherapeutic agents. However, there are no effective strategies to treat the neuropathy. We examined whether Goshajinkigan, a herbal medicine, would prevent paclitaxel-induced allodynia without affecting the anticancer action in mice. Murine breast cancer 4T1 cells were inoculated into the mammary fat pad. Paclitaxel (10 and 20 mg/kg, intraperitoneal, alternate day from day 7 postinoculation) inhibited the tumor growth, and Goshajinkigan (1 g/kg, oral, daily from day 2 postinoculation) did not affect the antitumor action of paclitaxel. Mechanical allodynia developed in the inoculated region due to tumor growth and in the hind paw due to paclitaxel-induced neuropathy. Paclitaxel-induced allodynia was markedly prevented by Goshajinkigan, although tumor-associated allodynia was not inhibited by Goshajinkigan. These results suggest that Goshajinkigan prevents paclitaxel-induced peripheral neuropathy without interfering with the anti-cancer action of paclitaxel.

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Letter to the Editor: 1H, 15N and 13C resonance assignment of human ?S-crystallin, a 21�kDa eye-lens protein

Journal of Biomolecular NMR ◽

10.1007/s10858-004-3497-3 ◽

2004 ◽

Vol 30 (3) ◽

pp. 385-386 ◽

Cited By ~ 2

Author(s):

Carine Baraguey ◽

F�riel Skouri-Panet ◽

Fran�ois Bontems ◽

Annette Tardieu ◽

G�rard Chassaing ◽

...

Keyword(s):

Resonance Assignment ◽

Eye Lens ◽

Lens Protein ◽

Letter To The Editor ◽

Eye Lens Protein

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Catalysis of cataract-associated human γD crystallin aggregation via dynamic disulfide exchange

10.1101/300608 ◽

2018 ◽

Author(s):

Eugene Serebryany ◽

Shuhuai Yu ◽

Sunia A. Trauger ◽

Bogdan Budnik ◽

Eugene I. Shakhnovich

Keyword(s):

Light Scattering ◽

Disulfide Bond ◽

Eye Lens ◽

Lens Protein ◽

Biochemical Mechanism ◽

Wild Type ◽

Disulfide Exchange ◽

Mechanism Of Catalysis ◽

Eye Lens Protein

AbstractSeveral mutations in human γD-crystallin (HγD), a long-lived eye lens protein, cause misfolding and aggregation, leading to cataract. Surprisingly, wild-type HγD catalyzes aggregation of its cataract related W42Q variant while itself remaining soluble – the inverse of the classical prion-like scenario whereby misfolded polypeptides catalyze aggregation of natively folded ones. The search for a biochemical mechanism of catalysis of W42Q aggregation by WT has revealed that WT HγD can transfer a disulfide bond to the W42Q variant. The transferred disulfide kinetically traps an aggregation-prone intermediate made accessible by the W42Q mutation, facilitating light-scattering aggregation of the W42Q variant. The aggregating variant thus becomes a disulfide sink, removing the disulfides from solution. Such redox “hot potato” competitions among wild-type and mutant or modified polypeptides may be relevant for many long-lived proteins that function in oxidizing environments. In these cases aggregation may be forestalled by inhibiting disulfide flow toward damaged polypeptides.

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Chronic inflammatory demyelinating polyradiculoneuropathy induced by paclitaxel

10.5327/1516-3180.413 ◽

2021 ◽

Author(s):

Isabella Sabião Borges ◽

João Victor Aguiar Moreira ◽

Eustaquio Costa Damasceno Junior ◽

Alencar Pereira dos Santos ◽

Gabriela Tomás Alves ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Glial Cells ◽

Conduction Block ◽

Chemotherapeutic Agents ◽

Chronic Inflammatory Demyelinating Polyradiculoneuropathy ◽

Microtubule Stabilization ◽

Progressive Muscle Weakness ◽

History Of ◽

Secondary Demyelination ◽

Distal Axonal Degeneration

Background: Peripheral neuropathies in cancer are most often due to neurotoxic chemotherapeutic agents. Approximately 30% of patients receiving neurotoxic chemotherapy (CTX) will suffer from chemotherapy-induced peripheral neuropathy (CIPN). Paclitaxel is an extremely effective chemotherapeutic agent for the treatment of breast, ovarian, and lung cancer. However, paclitaxel-induced peripheral neuropathy occurs in 59-87% of patients who receive this drug. Paclitaxel is an anti-tubulin drug that causes microtubule stabilization, resulting in distal axonal degeneration, secondary demyelination and nerve fiber loss. Case: We present a case of a 68-year-old female patient with history of breast cancer who presented sensorial ataxia and progressive muscle weakness two months after starting CTX with paclitaxel. The physical examination showed tetraparesis with proximal predominance, areflexia, severe hypopalesthesia and postural instability. Electroneuromyography showed the existence of asymmetric demyelinating polyradiculoneuropathy, with conduction block and temporal dispersion in practically all evaluated nerves. The cerebrospinal fluid confirmed the albumin-cytological dissociation. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was confirmed and patient underwent monthly treatment with methylprednisolone with good response. Discussion: Evidences has implicated neuroinflammation in the development of PIPN. While most CTX drugs do not cross the blood-brain-barrier, they readily penetrate the blood-nerve-barrier and bind to and accumulate in dorsal root ganglia and peripheral axons. CTX can induce neuroinflammation through activation of immune and immune- like glial cells. In fact, immune cells (e.g., macrophages, lymphocytes) and glial cells (e.g., Schwann cells) in the peripheral nervous system play important role in the induction and maintenance of neuropathy. Conclusion: CIDP should be included in the spectrum of CIPN.

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