Ameliorative potential of ferulic acid in vincristine-induced painful neuropathy in rats: An evidence of behavioral and biochemical examination

Abstract

The present study was designed to investigate the effect of ferulic acid (FA) in vincristine-induced neuropathic pain in rats. Vincristine (50 µg/kg, i.p. for 10 consecutive days) was administered to induce painful neuropathy in rats. Various pain sensitive tests, viz., pinprick, hot plate, paint-brush, and acetone test were performed on different days (1, 6, 14, and 21) to assess the degree of mechanical hyperalgesia, heat hyperalgesia, mechanical dynamic allodynia, and cold allodynia, respectively. The electrophysiological and histopathological evaluations were also investigated. The tissue thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), and total calcium were measured as the markers of inflammation and oxidative stress. FA (50 and 100 mg/kg, i.p.) and gabapentin (10 mg/kg, p.o.) were administered for 11 days. Administration of FA attenuated the vincristine-induced behavioral alteration along with electrophysiological and histopathological changes significantly (P < 0.05). FA also attenuated the vincristine-induced oxidative stress (TBARS, GSH, and total calcium levels) and inflammation (MPO, TNF-alpha, IL-6, and IL-10). It may be concluded that FA has ameliorative potential in mitigation of the painful states associated with vincristine-induced painful neuropathy that may further be attributed to anti-inflammatory actions with subsequent reduction in oxidative stress.

Peripheral Analgesic Effect and Possible Mechanisms of Ferulic Acid

“…This outcome coincides with the results of similar studies conducted. [14][15][16] The effect of plants that are used for their analgesic effect in traditional medicine may be, therefore, originating from ferulic acid. For instance, blueberries (Vaccinium corymbosum), which were shown to exhibit analgesic effect 27 , were reported to contain 66.5-68.3% of ferulic acid.…”

“…Experimental studies have claimed that ferulic acid has an analgesic effect on pain induced by various pathways in different experimental models. [14][15][16] However, existing data regarding the antinociceptive mechanism of action of ferulic acid is limited.…”

The use of antioxidant agents for chemotherapy‐induced peripheral neuropathy treatment in animal models

“…Ferulic Acid (a phenolic phytochemical commonly found in fruits and vegetables) and Matrine (an alkaloid found in plants from the Sophora genus) were able to reduce the signs of vincristin‐induced peripheral neuropathy. The results were found through behavioural, electrophysiological, biochemical and histopathological analyses …”

Sub-Chronic Administration of Vincristine Sulfate Induces Renal Damage and Apoptosis in Rats via Induction of Oxidative Stress and Activation of Raf1-MEK1/2-Erk1/2 Signal Transduction

“…Vincristine (VCR) is a drug of plants origin with antineoplastic properties and is widely used for the treatment of numerous malignancies (Blasko & Cordel, 1990;Jordan, 2002). High capacity of binding of normal tissue to VCR results in high accumulation rate and limits its tumor tissue exposure leading to adverse cytotoxicity to non-neoplastic tissues (Martins et al, 2011;Kumar, 2016;Vashistha et al, 2017). Indeed, VCR accumulates at high rates in most organs and tissues with the exception of the brain, eye, and fat (Said & Tsimberidou, 2014;Khalil et al, 2016;Kumar).…”

“…VCR-induced tissue cytotoxicity is mediated mainly by induction of apoptosis (da Silva et al, 1996;Mollinedo & Gajate, 2003) and to a lesser extent by induction of necrosis (Kesik et al, 2010). CVR-induced apoptosis was found to be as a result of disruption of microtubules, arrest of cell cycle division during the metaphase, inhibition of synthesis of proteins and nucleic acids, and induction of oxidative stress and inflammation (Jordan;Mollinedo & Gajate;Muthuraman & Singh;Canta et al, 2015;Vashistha et al). However, VCR-induced necrosis is mainly mediated by interfering with vascular blood flow (Kesik et al).…”