Introduction: Cisplatin is an antineoplastic agent which is used in treatment of various cancers. However its clinical use is associated with oxidative stress-mediated neuropathic pain. This research aimed to explore the effect of silymarin on cisplatin-induced hyperalgesia (CIH) and oxidative stress biomarkers in male rats. Methods: Fifty-six male rats were allocated into seven equal groups. Hyperalgesia was caused by intraperitoneal single dose administration of cisplatin (1mg/kg) and assessed by utilizing tail-flick method. The impact of silymarin (25, 50 and 100 mg/kg/day for 15 days) on CIH was investigated on days 1, 5, 10 and 15. Blood samples were collected to assess malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD) and total antioxidant status (TAS) on day fifteen. Results: Single dose injection of cisplatin (1mg/kg) could cause a significant hyperalgesia on days 5, 10 and 15. CIH was abolished by daily administration of silymarin (50 and 100mg/kg) on days 10 and 15. Serum MDA level was decreased in cisplatin and silymarin (100 mg/kg) co-treated rats, while there was an increase in GPx, SOD as well as TAS parameters. Conclusion: The results of this study revealed that silymarin prevents from CIH possibly by improving lipid peroxidation and oxidative stress biomarkers. Other clinical studies should be performed to establish possible use of silymarin for treatment of CIH in susceptible individuals.
Background: Coumestrol is well-known as a natural estrogen receptor-beta modulator. Since the role of estrogen receptors in controlling stressful situations has already been reported and their cognitive functions in hippocampus seem to be independent of sexual tasks, the aim of this study was to investigate the improving effects of this phytoestrogen on negative consequences of exposing male mice to chronic restraint stress. Methods: This study was divided into two separate but consecutive phases. In the first phase, the possible effects of Coumestrol (30, 60, 120 µg.kg-1.day-1, i.p.) and its vehicle (sesame oil) on restraint stress-induced cognitive impairments, oxidative stress and apoptosis were evaluated. During the second phase, a selective estrogen receptor-beta antagonist was used to investigate the possible involvement of beta-type estrogen receptors in these processes. Morris water maze and novel object recognition tests were performed to evaluate memory while elevated plus maze test was used to measure the level of anxiety. Spectroscopy and western blotting methods were also employed to evaluate oxidative and apoptotic status in hippocampal tissue. Furthermore, serum level of corticosterone was measured for each group. Results: Behavioral tests indicated memory enhancing and anxiolytic effects of coumestrol. Biochemical evaluations also proved its antioxidant and anti-apoptotic potential. On the other hand, the mentioned behavioral and biochemical improvements were reversed in the group treated with estrogen receptor-beta antagonist. Conclusion: Coumestrol may ameliorate negative consequences of exposure to chronic stress such as oxidative stress, apoptosis and cognitive impairments, via the modulation of beta-type estrogen receptors in hippocampus.
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