RESUMEN
AIM: To evaluate the effects of tramadol on inflammation by measuring NLRP1 and IL-1 beta (IL-1ß) levels in an experimental neuropathic pain model. MATERIAL AND METHODS: Sprague-Dawley rats were divided into three groups: control, chronic constriction injury (CCI), and CCI + tramadol. Neuropathic pain was assessed using mechanical allodynia, thermal hyperalgesia, and cold allodynia. IL-1ß and NLRP1 levels were evaluated using ELISA on sciatic nerve (SN), dorsal root ganglion (DRG), and serum either on day 3 or days 8 postsurgery. RESULTS: On day 3, paw withdrawal latency (PWL) was lower in the CCI and CCI + tramadol groups than the control group in both mechanical and cold allodynia tests. On day 8, the PWL in the CCI group was also lower than in the control group. In contrast, tramadol increased the PWL on day 8 compared to day 3 in the CCI group. During cold allodynia, PWL decreased in the CCI group, however, tramadol reversed this effect on days 3 and 8. Tramadol, therefore, ameliorated pain hypersensitivity in mechanical/cold allodynia tests. Serum IL-1ß levels were higher in the CCI + tramadol and CCI groups than the control group, although serum IL-1ß levels in the CCI and CCI + tramadol groups were comparable. Tramadol decreased the IL-1ß and NLRP1 in DRG compared with the CCI group. A similar trend was observed in the SN samples. CONCLUSION: Our experiments revealed an increase in IL-1ß and NLRP-1 levels in a neuropathic pain model and found that tramadol had an anti-inflammatory effect on the IL-1ß and NLRP1 inflammasomes.
Asunto(s)
Modelos Animales de Enfermedad , Hiperalgesia , Inflamasomas , Interleucina-1beta , Neuralgia , Ratas Sprague-Dawley , Tramadol , Animales , Tramadol/farmacología , Tramadol/uso terapéutico , Interleucina-1beta/metabolismo , Interleucina-1beta/sangre , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismo , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Masculino , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Ratas , Analgésicos Opioides/farmacología , Nervio Ciático/efectos de los fármacos , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas del Tejido NerviosoRESUMEN
This study aimed to evaluate the protective effect of taurine (TAU) with regard to antioxidant, anti inflammatory and antiapoptotic pathways on cyclophosphamide (CP)-induced testicular toxicity in rats. Forty Sprague-Dawley male rats were used in this experimental study. The CP group animals received a single dose of 200mg/kg CP on Day 8 intraperitoneally (i.p). The other groups were treated with TAU (75, 150 and 300mg/kg) orally for 14 days prior to and following a single i.p injection of CP. Morphometrical analysis and histological examination of testicular tissue were performed. Serum testosterone, LH and FSH levels were measured in serum using commercial ELISA kits. The testicular injury induced by CP was evaluated in terms of oxidative stress, inflammation and apoptosis with a significant inflammatory and apoptotic response and an insignificant oxidative stress. TAU treatment resulted in improvement in body weight gain, oxidative stress, inflammation and apoptosis, some of which were significant. The improvement was more pronounced for antiapoptotic effect of taurine in the testis of CP-treated animals. It was concluded that TAU may prevent and/or treat the testicular toxicity by ameloirating oxidative stress, inflammation and apoptosis.
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Taurina , Testículo , Ratas , Masculino , Animales , Testículo/metabolismo , Ratas Sprague-Dawley , Taurina/farmacología , Ciclofosfamida/toxicidad , Antioxidantes/metabolismo , Estrés Oxidativo , Inflamación/metabolismoRESUMEN
l-Arginine, a nitric oxide (NO) donor; sodium hydrosulfide (NaHS), a hydrogen sulfide (H2 S) donor; and tricarbonyldichlororuthenium(II) dimer (CORM-2), carbon monoxide (CO) donor, are characterized as bioactive gas mediators that have been researched for their roles in human physiology. This study aimed to compare the effects of these mediators on pain, anxiety, and depression. Ninety-one adult male Sprague-Dawley rats were used for the experiments. Locomotor activity, elevated plus maze, forced swimming, tail clip, hot plate, and writhing tests were used for the assessments after the administration of l-arginine (30-100 mg/kg), a NO donor; NaHS (5-10 mg/kg), a H2 S donor; and CORM-2 (5-10 mg/kg), CO donor. Intraperitoneal H2 S, NO, malondialdehyde (MDA), glutathione (GSH), and tumor necrosis factor-α (TNF-α) levels were determined by enzyme-linked immunosorbent assay (ELISA). No statistical significance was found in the locomotor activity. NO and CO significantly extended latency at high doses in tail clip test. No significant activity was observed at any dose of all three substances on a hot plate. Both doses of CO and high doses of NO and H2 S showed an antinociceptive effect in the writhing test. While the opioidergic system plays a role in the spinal antinociceptive effect of l-arginine, both serotonergic and opioidergic systems play a role in its peripheral antinociceptive effect. The serotonergic system plays a role in the peripheral antinociceptive effect of CORM-2. The time spent in open arm increased significantly in all groups an elevated plus maze. High doses of all three substances significantly increased the duration of immobility in the forced swimming test. No statistical significance was observed in MDA, GSH, and TNF-α levels. High doses of NO and CO showed a spinal antinociceptive effect. Both doses of CO and high doses of NO and H2 S showed a peripheral antinociceptive effect. All three agents showed anxiolytic and depression-like effects.
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Monóxido de Carbono , Sulfuro de Hidrógeno , Óxido Nítrico , Analgésicos/farmacología , Animales , Ansiolíticos/farmacología , Arginina , Monóxido de Carbono/farmacología , Depresión/tratamiento farmacológico , Sulfuro de Hidrógeno/farmacología , Masculino , Óxido Nítrico/farmacología , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfaRESUMEN
AIM OF THE STUDY: Cisplatin is a platinum-derived chemotherapeutic agent commonly used in the treatment of various tumors. Ototoxicity, nephrotoxicity, and peripheral neuropathy are the most common side effects of this drug. 2-Aminoethoxydiphenyl borate (2-APB), boron- containing compound, has some protective effects against various tissue damage. The present study aimed to investigate the potential protective effects of 2-APB on in vitro and in vivo cisplatin-induced neurotoxicity. MATERIALS AND METHODS: MTT assay was used to determine cell viability in DRG cells. Peripheral neuropathy was induced in forty male Sprague-Dawley rats (200-250g) by administering cisplatin (3 mg/kg/week) intraperitoneally (i.p) for five weeks. 2-APB (2, 4, and 8 mg/kg, i.p) was administered. Mechanical allodynia, thermal hyperalgesia, cold allodynia, mechanical stimuli, motor coordination, and locomotor activity tests were performed. DRG cells and sciatic nerves were analyzed histologically. NGF, BDNF, TNF-α, GSH, MDA, and LDH levels were investigated in rat DRG tissue homogenates. RESULTS: Our results revealed that 2-APB ameliorated cisplatin-induced neurotoxicity by improving mechanical and cold allodynia and motor coordination impairment. It also reduced cisplatin-induced structural toxicity in peripheral tissues. CONCLUSION: These findings demonstrated that 2-APB could be considered as a potential therapeutic strategy for the treatment of cisplatin-induced peripheral neuropathy.
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Antineoplásicos , Enfermedades del Sistema Nervioso Periférico , Animales , Antineoplásicos/efectos adversos , Compuestos de Boro/efectos adversos , Cisplatino/efectos adversos , Masculino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Ratas , Ratas Sprague-DawleyRESUMEN
The study aims to establish how feasible a natural therapy option (safflower oil) is in the treatment of postoperative pain. Naproxen sodium has already been experimentally proven to be effective for this purpose. Accordingly, the analgesic and anti-inflammatory effects of safflower oil were compared with those obtained with benzydamine HCl and naproxen sodium. Forty-two, healthy, adult female rats of Wistar albino species were divided at random into six groups of seven rats. The intervention allocation was as follows: Group No. 1-physiological saline 0.9%; Group No. 2-safflower oil 100 mg/kg; Group No. 3-safflower oil 300 mg/kg; Group No. 4-benzydamine HCl 30 mg/kg; Group No. 5-benzydamine HCl 100 mg/kg; and Group No. 6-naproxen sodium 10 mg/kg. Following allocation of treatment, pain was induced experimentally and tested in various ways (hot plate test, tail-pinching test, and writhing test) and the efficacy of each treatment in providing peripheral and central analgesia was evaluated. The second stage consisted of providing different treatments to four groups (groups 7-10) of seven rats each, chosen at random. The allocations were as follows: Group No. 7-physiological saline 0.9%; Group No. 8-safflower oil 300 mg/kg; Group No. 9-benzydamine HCl 100 mg/kg; and Group No. 10-naproxen sodium 10 mg/kg. To create experimental inflammation, 2% formaldehyde was injected into the experimental animal's paw and the resulting edema was measured and recorded for a 10-day period. Edema inhibition was calculated as a percentage. The rats were sacrificed and the paw and stomach dissected for histopathological examination. The data were used for statistical analysis, using the Shapiro-Wilk, Kruskal-Wallis H test, and two-way analysis of variance. In the tail-pinching test, it was determined that a 300 mg/kg dose of safflower oil shows central spinal analgesic efficacy and this effect is close in magnitude to 10 mg/kg of the reference material, naproxen sodium. In the squirming test, it was observed that the 100 and 300 mg/kg doses of safflower oil had a peripheral analgesic effect when compared with the serum physiological (placebo) group. The peripheral efficacy of 300 mg/kg safflower oil was found to approximate that of 10 mg/kg naproxen sodium. In rats treated with benzydamine HCl 100 mg/kg, similar peripheral analgesic efficacy to naproxen sodium 10 mg/kg was noted. In the hot plate test, no difference in the analgesic efficacy between the various agents was found. The change in inhibition of edema between the 1st and 10th days was most marked in rats receiving naproxen sodium 10 mg/kg. A significant difference was determined in the safflower oil 300 mg/kg and benzydamine HCl 100 mg/kg groups (P < .001). Regarding histopathology findings in the rat paw, significant differences were seen in venous congestion between placebo and safflower oil 300 mg/kg and in inflammation between the control and benzydamine HCl 100 mg/kg groups. Regarding the histopathology findings in the rat stomach, significant differences were observed in venous congestion between placebo and safflower oil 300 mg/kg; in damage to the epithelium between placebo and safflower oil 300 mg/kg and between naproxen sodium 10 mg/kg and safflower oil; and in cell infiltration and development of edema between placebo and safflower oil 300 mg/kg. It is predicted that further research into safflower oil and benzydamine HCl will create opportunities to develop analgesic-anti-inflammatory therapeutics of a novel kind for the treatment of postoperative pain and inflammation.