scholarly journals Effect of Flavone Derivatives on Vincristine and Oxaliplatin Induced Peripheral Neuropathy in Mice

2021 ◽  
Author(s):  
Parimala Kathirvelu ◽  
Jagan Nadipelly ◽  
Vijaykumar Sayeli ◽  
Viswanathan Subramanian ◽  
Jaikumar Shanmugasundaram ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Mechanical Allodynia ◽  
Antinociceptive Effect ◽  
Thermal Hyperalgesia ◽  
Chemotherapeutic Agents ◽  
Hot Water ◽  
Cold Allodynia ◽  
Hydroxy Flavone ◽  
Flavone Derivatives ◽  
Anti Inflammatory

Introduction: Therapy with anticancer drugs like paclitaxel, platinum complexes and vincristine result in severe peripheral neuropathy. Very few treatment options are available to overcome this debilitating side effect. Flavone and its monohydroxy derivatives have been proved to possess anti-nociceptive and anti-inflammatory effects in animal models. Aim: To investigate flavone, 5-hydroxy flavone, 6-hydroxy flavone and 7-hydroxy flavone for their effect on neuropathy induced by vincristine and oxaliplatin in mice. Materials and Methods: In this experimental animal study, neuropathy was induced in mice by multiple doses of vincristine or a single dose of oxaliplatin. The manifestations of mechanical allodynia, cold allodynia and thermal hyperalgesia were measured by von Frey’s hair aesthesiometer, acetone spray test and hot water tail immersion test. The data was subjected to ANOVA followed by Dunnett’s test for multiple comparison and paired t-test at appropriate places. Results: Flavone and monohydroxy flavones significantly reduced the paw withdrawal response scores due to mechanical allodynia and cold allodynia resulting from vincristine or oxaliplatin administration (p<0.05). The tail withdrawal latency due to thermal hyperalgesia was also significantly increased by different flavone derivatives (p<0.05). However, 7-hydroxy flavone was ineffective in oxaliplatin-induced mechanical allodynia and vincristine induced thermal hyperalgesia. Analysis of the results indicated that the manifestations of neuropathy induced by vincristine or oxaliplatin were amenable to treatment with flavone derivatives in the following order; cold allodynia>thermal hyperalgesia>mechanical allodynia. Opioid mediated antinociceptive effect, interaction with cation channels and anti-inflammatory effect of the investigated flavones may be suggested as possible mechanisms for their beneficial effects in neuropathy due to chemotherapeutic agents. Conclusion: Various neuropathic manifestations induced by vincristine and oxaliplatin were effectively attenuated by flavone and monohydroxy flavones.

scholarly journals Nuclear PPAR-γ Activation Modulates Inflammation and Oxidative Stress in Attenuating Chemotherapy-Induced Neuropathic Pain in Vivo

2021 ◽  
pp. 167-179
Author(s):  
Haritha Pasupulati ◽  
Satyanarayana S. V. Padi ◽  
Sujatha Dodoala ◽  
Prasad V. S. R. G. Koganti
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Mechanical Allodynia ◽  
Antinociceptive Effect ◽  
Thermal Hyperalgesia ◽  
Ppar Γ ◽  
Markers Of Inflammation ◽  
And Oxidative Stress

Background: Paclitaxel-induced painful neuropathy is a major dose-limiting side effect and can persist for up to two years after completing treatment that greatly affects both the course of chemotherapy and quality of life in cancer patients. Peroxisome proliferator-activated receptor (PPAR)-γ belongs to a family of nuclear receptors known for their transcriptional and regulatory roles in metabolism, inflammation, and oxidative stress. However, the role of PPAR-γ activation on paclitaxel-induced neuropathic pain is not yet known. Objective: To investigate whether pioglitazone, a PPAR-γ agonist reduce paclitaxel-induced neuropathic pain and to elucidate underlying mechanisms. Methodology: Peripheral neuropathy was induced by administration of paclitaxel (2 mg/kg per injection) intraperitoneally on four alternate days (days 0, 2, 4, 6). Thermal hyperalgesia and mechanical allodynia were assessed and the markers of inflammation and nitroso-oxidative stress were estimated. Results: Pioglitazone did not induce hypoalgesia and had no effect on locomotor activity. Repeated oral administration of pioglitazone (10 and 20 mg/kg,) for 2 weeks started 14 days after paclitaxel injection markedly attenuated paw withdrawal responses to thermal (hyperalgesia) and mechanical (allodynia) stimuli. Further, pioglitazone administration significantly reduced elevated level of pro-inflammatory cytokine, TNF-α, in both the dorsal root ganglia and the spinal cord accompanied by marked decrease in oxidative stress parameters as well as increase in activity of antioxidant defense enzyme, superoxide dismutase, in the spinal cord after paclitaxel injection. Conclusion: The results of the present study demonstrate that pioglitazone, a PPAR-γ agonist exerted antinociceptive effect in paclitaxel-induced neuropathic pain through inhibiting neuroimmune inflammation in both the periphery and spinal cord and by reducing nitroso-oxidative stress in spinal cord. Our findings strongly suggest pharmacological activation of PPAR-g as a promising therapeutic target in paclitaxel-induced peripheral neuropathy and provide rationale for the clinical evaluation.

Effect of flavonol and its dimethoxy derivatives on paclitaxel-induced peripheral neuropathy in mice

2018 ◽  
Vol 29 (5) ◽  
pp. 525-535 ◽  
Author(s):  
Vijaykumar Sayeli ◽  
Jagan Nadipelly ◽  
Parimala Kadhirvelu ◽  
Binoy Varghese Cheriyan ◽  
Jaikumar Shanmugasundaram ◽  
...  
Keyword(s):  
Free Radicals ◽  
Peripheral Neuropathy ◽  
Proinflammatory Cytokines ◽  
Interleukin 1 ◽  
Thermal Hyperalgesia ◽  
Hot Water ◽  
Tactile Allodynia ◽  
Dependent Manner ◽  
Cold Allodynia ◽  
Tnf Α

AbstractBackground:Peripheral neuropathy is the dose limiting side effect of many anticancer drugs. Flavonoids exhibit good antinociceptive effect in animal models. Their efficacy against different types of nociception has been documented. The present study investigated the effect of flavonol (3-hydroxy flavone), 3′,4′-dimethoxy flavonol, 6,3′-dimethoxy flavonol, 7,2′-dimethoxy flavonol and 7,3′-dimethoxy flavonol against paclitaxel-induced peripheral neuropathy in mice.Methods:A single dose of paclitaxel (10 mg/kg, i.p.) was administered to induce peripheral neuropathy in mice and the manifestations of peripheral neuropathy such as tactile allodynia, cold allodynia and thermal hyperalgesia were assessed 24 h later by employing Von Frey hair aesthesiometer test, acetone bubble test and hot water tail immersion test, respectively. The test compounds were prepared as a suspension in 0.5% carboxymethyl cellulose and were administered s.c. in various doses (25, 50, 100 and 200 mg/kg). The above behavioral responses were assessed prior to and 30 min after drug treatment. In addition, the effect of test compounds on proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β) and free radicals was investigated by using suitablein vitroassays.Results:A dose-dependent attenuation of tactile allodynia, cold allodynia and thermal hyperalgesia was evidenced in mice treated with flavonol derivatives. The test compounds inhibited TNF-α, IL-1β and free radicals in a concentration-dependent manner.Conclusions:These results revealed that flavonol and its dimethoxy derivatives ameliorated the manifestations of paclitaxel-induced peripheral neuropathy in mice. The inhibition of proinflammatory cytokines and free radicals could contribute to this beneficial effect.

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

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
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.

The Effect of Electroconvulsive Treatment on Thermal Hyperalgesia and Mechanical Allodynia in a Rat Model of Peripheral Neuropathy

1998 ◽  
Vol 86 (3) ◽  
pp. 584-587 ◽  
Author(s):  
Masahiko Shibata ◽  
Satoshi Wakisaka ◽  
Takaya Inoue ◽  
Tadao Shimizu ◽  
Ikuto Yoshiya
Keyword(s):  
Peripheral Neuropathy ◽  
Rat Model ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Electroconvulsive Treatment

scholarly journals Preconditioning with hydrogen sulfide prevents bone cancer pain in rats through a proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway

2017 ◽  
Vol 243 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Li Zhuang ◽  
Ke Li ◽  
Gaowei Wang ◽  
Tao Shou ◽  
Chunlin Gao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cancer Pain ◽  
Rat Model ◽  
Mechanical Allodynia ◽  
Antinociceptive Effect ◽  
Thermal Hyperalgesia ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Kinase Pathway

Bone cancer pain (BCP) is a severe type of hyperpathic pain occurring with primary bone tumors or advanced cancers which metastasize to bones. BCP can detrimentally reduce quality of life and presents a challenge to modern medicine. Studies have shown that exogenous H2S may act as a neuroprotectant to protect against some diseases in central nervous system. The preset study aimed to investigate the antinociceptive effect of H2S in BCP. We first measured the changes of serum H2S in patients with BCP and analyzed the relationship between them, then investigated the effect of H2S preconditioning on BCP, and explored the mechanism in rat model. Our results revealed that serum H2S level was negatively correlated with pain scores. In the rat model of BCP, preconditioning with H2S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. The mechanism of H2S preconditioning may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. Impact statement Bone cancer pain (BCP) significantly decreases the life quality of patients or their life expectancy and causes a severe health burden to the society. However, as the exact mechanism of BCP is still poorly understood, no effective treatment has been developed yet. There are some pain medicines now, but they have some inevitable side effects. Additional therapeutic strategies are urgently needed. First, we revealed that preconditioning with H2S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. Second, the mechanism of H2S preconditioning was elucidated. It may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. This novel finding may significantly help us to understand the difference between the roles of endogenous H2S and exogenous H2S in the development of BCP and present us a new strategy of pain management.

scholarly journals The Protective Effect of Bergamot Polyphenolic Fraction (BPF) on Chemotherapy-Induced Neuropathic Pain

2021 ◽  
Vol 14 (10) ◽  
pp. 975
Author(s):  
Sara Ilari ◽  
Filomena Lauro ◽  
Luigino Antonio Giancotti ◽  
Valentina Malafoglia ◽  
Concetta Dagostino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Glutamate Transporter ◽  
Thermal Hyperalgesia ◽  
Chemotherapeutic Agents ◽  
Preventive Strategy ◽  
Polyphenolic Extract ◽  
Thermal Hypersensitivity

Paclitaxel is a chemotherapeutic drug used for cancer treatment. Chemotherapy-induced peripheral neuropathy (CIPN) is a common major dose-limiting side effect of many chemotherapeutic agents, including paclitaxel. CIPN is accompanied by mechanical and thermal hypersensitivity that resolves within weeks, months, or years after drug termination. To date, there is no available preventive strategy or effective treatment for CIPN due to the fact that its etiology has not been fully explained. It is clear that free radicals are implicated in many neurodegenerative diseases and recent studies have shown the important role of oxidative stress in development of CIPN. Here, we observed how, in rats, the administration of a natural antioxidant such as the bergamot polyphenolic extract (BPF), can play a crucial role in reducing CIPN. Paclitaxel administration induced mechanical allodynia and thermal hyperalgesia, which began to manifest on day seven, and reached its lowest levels on day fifteen. Paclitaxel-induced neuropathic pain was associated with nitration of proteins in the spinal cord including MnSOD, glutamine synthetase, and glutamate transporter GLT-1. This study showed that the use of BPF, probably by inhibiting the nitration of crucial proteins involved in oxidative stress, improved paclitaxel-induced pain behaviors relieving mechanical allodynia, thermal hyperalgesia, thus preventing the development of chemotherapy-induced neuropathic pain.

The Effect of Electroconvulsive Treatment on Thermal Hyperalgesia and Mechanical Allodynia in a Rat Model of Peripheral Neuropathy

1998 ◽  
Vol 86 (3) ◽  
pp. 584-587 ◽  
Author(s):  
Masahiko Shibata ◽  
Satoshi Wakisaka ◽  
Takaya Inoue ◽  
Tadao Shimizu ◽  
Ikuto Yoshiya
Keyword(s):  
Peripheral Neuropathy ◽  
Rat Model ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Electroconvulsive Treatment

Buddleja thyrsoides Lam. crude extract presents antinociceptive effect on an arthritic pain model in mice

2017 ◽  
Vol 474 (17) ◽  
pp. 2993-3010 ◽  
Author(s):  
Maria Fernanda Pessano Fialho ◽  
Indiara Brusco ◽  
Evelyne da Silva Brum ◽  
Mariana Piana ◽  
Aline Augusti Boligon ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Crude Extract ◽  
Topical Treatment ◽  
Oral Treatment ◽  
Antinociceptive Effect ◽  
Thermal Hyperalgesia ◽  
Chronic Inflammatory Disease ◽  
Stability Study ◽  
Pain Model ◽  
Anti Inflammatory

Arthritis is a chronic inflammatory disease which reduces the life quality of affected individuals. Therapeutic tools used for treating inflammatory pain are associated with several undesirable effects. Buddleja thyrsoides Lam., known as ‘Barbasco’ or ‘Cambara’, is mostly used in several disorders and possesses antirheumatic, anti-inflammatory, and analgesic properties. Here, we investigated the antinociceptive and anti-inflammatory effects of the B. thyrsoides crude extract applied orally and topically in acute pain models and an arthritic pain model induced by complete Freund's adjuvant (CFA) paw injection in male mice (25–30 g). The high-performance liquid chromatography (HPLC) of the B. thyrsoides extract crude revealed the presence of the lupeol, stigmasterol, and β-sitosterol. The stability study of the B. thyrsoides gel did not show relevant changes at low temperatures. The oral treatment with the B. thrysoides extract prevented the capsaicin-induced spontaneous nociception and the acetic acid-induced abdominal writhing, but did not alter the thermal threshold in the tail immersion test. The B. thyrsoides antinociceptive effect was not reversed by naloxone in the capsaicin test. The B. thyrsoides oral or topical treatment reversed the CFA-induced mechanical allodynia and thermal hyperalgesia with maximum inhibition (Imax) of 69 ± 6 and 68 ± 5% as well as 78 ± 15 and 87 ± 12%, respectively. Moreover, the topical but not oral treatment inhibited the CFA-induced cell infiltration, but did not reduce the paw edema significantly. The oral treatment with B. thyrsoides did not cause adverse effects. These findings suggest that the oral or topical treatment with B. thyrsoides presents antinociceptive actions in an arthritic pain model without causing adverse effects.

scholarly journals Antiallodynic and anti-inflammatory effects of intrathecal R-PIA in a rat model of vincristine-induced peripheral neuropathy

2020 ◽  
Vol 73 (5) ◽  
pp. 434-444 ◽  
Author(s):  
Kyungmi Kim ◽  
Wonyeong Jeong ◽  
In Gu Jun ◽  
Jong Yeon Park
Keyword(s):  
Peripheral Neuropathy ◽  
Rat Model ◽  
Thermal Hyperalgesia ◽  
Mechanical Hyperalgesia ◽  
Cold Allodynia ◽  
Adenosine A1 Receptors ◽  
Tnf Α ◽  
Adenosine A1 ◽  
Α Level ◽  
Antiallodynic Effect

Background: Studies investigating the correlation between spinal adenosine A1 receptors and vincristine-induced peripheral neuropathy (VIPN) are limited. This study explored the role of intrathecal N6-(2-phenylisopropyl)-adenosine R-(-)isomer (R-PIA) in the rat model of VIPN. Methods: Vincristine (100 μg/kg) was intraperitoneally administered for 10 days (two 5-day cycles with a 2-day pause) and VIPN was induced in rats. Pain was assessed by evaluating mechanical hyperalgesia, mechanical dynamic allodynia, thermal hyperalgesia, cold allodynia, and mechanical static allodynia. Biochemically, tumor necrosis factor-alpha (TNF-α) level and myeloperoxidase (MPO) activity were measured in the tissue from beneath the sciatic nerve.Results: Vincristine administration resulted in the development of cold allodynia, mechanical hyperalgesia, thermal hyperalgesia, mechanical dynamic allodynia, and mechanical static allodynia. Intrathecally administered R-PIA (1.0 and 3.0 μg/10 μl) reversed vincristine-induced neuropathic pain (cold and mechanical static allodynia). The attenuating effect peaked 15 min after intrathecal administration of R-PIA after which it decreased until 180 min. However, pretreatment with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 μg/10 μl) 15 min before intrathecal R-PIA administration significantly attenuated the antiallodynic effect of R-PIA. This antiallodynic effect of intrathecal R-PIA may be mediated through adenosine A1 receptors in the spinal cord. Intrathecally administered R-PIA also attenuated vincristine-induced increases in TNF-α level and MPO activity. However, pretreatment with intrathecal DPCPX significantly reversed this attenuation.Conclusions: These results suggest that intrathecally administered R-PIA attenuates cold and mechanical static allodynia in a rat model of VIPN, partially due to its anti-inflammatory actions.

scholarly journals Effect of xylopic acid on alloxan-induced diabetic neuropathy in rats

2021 ◽  
Vol 10 (4) ◽  
pp. 333
Author(s):  
Elvis Ofori Ameyaw ◽  
Ernest Obese ◽  
Du-Bois Asante ◽  
Robert P. Biney ◽  
Akua A. Karikari ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Diabetic Neuropathy ◽  
Cold Water ◽  
Thermal Hyperalgesia ◽  
Hot Water ◽  
Male Rats ◽  
Major Constituent ◽  
Diabetic Patients ◽  
Cold Allodynia ◽  
Liver And Kidney

Background: Neuropathic pain is a very disturbing condition commonly found in diabetic patients. This study investigated xylopic acid (XA), the major constituent of Xylopia aethiopica in diabetic neuropathy as well as established possible toxicity of the compound on some selected tissues.Methods: Diabetes was induced in six groups of male rats with 120 mg/kg alloxan monohydrate. Diabetes was confirmed as a blood glucose level >15 mmol/dl. Neuropathic pain was confirmed on day three post-diabetes induction and treatment with 10 mg/kg, 30 mg/kg or 100 mg/kg xylopic acid, 10 mg/kg glibenclamide, 10 mg/kg morphine, and 10 ml/kg normal saline were initiated and continued for the next 15 days. The effects of the treatments on cold allodynia (cold water at 4°C) and thermal hyperalgesia (hot water at 55 ± 1°C) were evaluated within the duration of treatments. Histology of the liver and kidney, as well as haematological, serum biochemical, and semen analyses, were done after the fifteenth day of the experiment.Results: Xylopic acid produced significant anti-hyperglycaemic and analgesic effects in the cold allodynia and thermal hyperalgesia tests. Sperm motility, viability and count were significantly restored at 10 mg/kg XA as compared higher doses and negative control. The outcome of haematological analysis revealed a protective effect of XA although histological damage liver and kidney due to alloxan treatment was observable.Conclusions: Xylopic acid ameliorates diabetic neuropathy in rats and does not exert detrimental effects at low doses.

Sign in / Sign up

Export Citation Format

Share Document