Cisplatin is a widely used antineoplastic agent in the treatment of various cancers. Peripheral neuropathy is a well-known side effect of cisplatin and has potential to result in limiting and/or reducing the dose, decreasing the quality of life. Thus, effective treatments are needed. Agmatine is an endogenous neuromodulator that has been shown to exert antiallodynic effects in various animal studies. The first aim of this study was to investigate the in vitro effects of agmatine on cisplatin-induced neurotoxicity. Primary cultures of dorsal root ganglia (DRG) which are the primary target of drug injury were prepared. DRG cells were incubated with cisplatin (100, 200, 500 μm). Then, agmatine (10, 100, 500 μm) was administered with the submaximal concentration of cisplatin. Cisplatin caused concentration-dependent neurotoxicity, and agmatine did not alter this effect. The second aim was to investigate the effects of agmatine on cisplatin-induced peripheral neuropathy in rats and the influence of nitric oxide synthase (NOS) inhibitor, L-NAME, in this effect. Female Sprague Dawley rats received intraperitoneal saline (control), cisplatin (3 mg/kg), cisplatin+agmatine (100 mg/kg), or cisplatin+agmatine+L-NAME (10 mg/kg) once a week for 5 weeks. The mechanical allodynia, hot plate, and tail clip tests were performed, and DRG cells and sciatic nerves were analyzed. Agmatine and agmatine+L-NAME combination attenuated CIS-induced mechanical allodynia and degeneration in DRG cells and sciatic nerves. However, L-NAME did not potentiate the antiallodynic or neuroprotective effect of agmatine. These findings indicate that agmatine co-administration ameliorates cisplatin-induced neuropathy and may be a therapeutic alternative.
Objective: The aim of the present study was to investigate the possible beneficial effects of resveratrol in mice subjected to vinyl cyclohexene dieposide (VCD) -induced testicular toxicity.
Material and methods:A total of thirty-six Swiss albino male mice aged 28-days were used in the present study. The study was composed of two stages where mice which received or did not receive VCD (320 mg/kg/day) were administered resveratrol. The animals were assigned into control and resveratrol-treated groups in the first stage and into groups of VCD-and VCD+resveratrol-treated groups in the second stage. At the end of the experiments, relative testicular weight (TW/BW) and dry/wet weight of testis (TDW/ TWW) were calculated. Histological analysis by hematoxylin and eosin (H&E) staining and immunohistochemical staining by BAX and Bcl-2 were performed. Serum testosterone, LH and FSH levels were measured by a commercially available ELISA kit.
Results:Resveratrol caused a dose-dependent increase in TW/BW and decrease in TDW/TWW (p<0.05).Resveratrol at a dose of 20 mg/kg resulted in an improvement in testosterone, LH and FSH levels in mice with VCD-induced testicular toxicity (p<0.001). Resveratrol also improved apoptotic index and epithelial cell height of testicular seminipherous tubuli significantly after VCD exposure (p<0.001).
Conclusion:Results of the present study suggest that resveratrol can be used as a protective and/or therapeutic agent particularly for cases with male infertility caused by testicular toxicity.
Cisplatin is a widely used antineoplastic agent in the treatment of various cancers. Peripheral neuropathy is a well-known side effect of cisplatin and has the potential to result in limiting and/or reducing the dose, decreasing the quality of life. Unfortunately, the mechanism for cisplatin-induced neuropathy has not been completely elucidated. Currently, available treatments for neuropathic pain (NP) are mostly symptomatic, insufficient and are often linked with several detrimental side effects; thus, effective treatments are needed. Cannabinoids and agmatine are endogenous modulators that are implicated in painful states. This review explains the cisplatin-induced neuropathy and antinociceptive effects of cannabinoids and agmatine in animal models of NP and their putative therapeutic potential in cisplatin-induced neuropathy.
By blocking L-type voltage-gated calcium channels, nimodipine did not prevent CDDP neurotoxicity in CGCs. Ca influx via these channels seemed to be insufficient to cause a change in CDDP-induced neurotoxicity. Similarly, glibenclamide failed to prevent CDDP neurotoxicity. Further studies are needed to elucidate the mechanisms of these preliminary results.
Agmatin, endojen katyonik bir amindir ve α2-adrenoseptörler, imidazolin bağlanma yerleri, NMDA reseptörleri ve nitrik oksit (NO) sentaz inhibisyonu aracılığıyla çeşitli nöroterapötik etkileri bildirilmiştir. NO'nun merkezi sinir sisteminde nöromodülatör ve nörotransmiter olarak görev yaptığı, konvülziyon modellerinde prokonvülsan/antikonvülsan aktiviteye sahip olduğu bildirilmiştir. Bu çalışmada, akut agmatin uygulamasının deneysel epilepsi modelindeki etkisi, etkisinin referans antiepileptiklerle karşılaştırılması ve nitrik oksit aracılı mekanizmaların katkısının araştırılması amaçlanmıştır.
Gereç ve yöntemler:Epilepsi nöbetleri, Swiss-albino farelerde tek doz pentilentetrazol (PTZ) (60mg/kg) enjeksiyonu ile indüklendi. Agmatin(10mg/kg), sodyum valproat (150mg/kg), gabapentin (20mg/kg) ve fenitoin (20mg/kg) tek başına veya nitrik oksit prekürsörü N(G)-Nitro-L-arginin-metil-ester (L-NA-ME,5mg/kg) ve spesifik olmayan NO sentaz inhibitörü L-arginin (L-Arg,60mg/kg) ile kombine edilerek intraperitoneal olarak PTZ' den önce tek doz enjekte edildi. Jeneralize tonik-klonik nöbetler (generalized tonic clonic seizures) (GTCS) ve miyoklonik sıçramalar (myoclonic jerks) (MJ), koruma yüzdesi ve ölüm oranları kaydedildi.Bulgular: Agmatin, kontrole göre GTCS ve MJ yüzdesini azaltırken koruma yüzdesini anlamlı ölçüde arttırdı. Sodyum valproat sadece GTCS yüzdesini kontrole göre anlamlı ölçüde azaltırken, MJ ve koruma yüzdelerini değiştirmedi. Fenitoin ve gabapentin GTCS, MJ ve koruma yüzdelerini kontrole göre değiştirmedi. L-Arg, agmatinin MJ ve koruma yüzdeleri üzerindeki etkisini anlamlı ölçüde tersine çevirdi. Hem L-Arg hem de L-NAME, sodium valproat ve fenitoinin GTCS, MJ ve koruma yüzdeleri üzerindeki etkisini değiştirmedi. L-Arg, gabapentinin GTCS, MJ ve koruma yüzdeleri üzerindeki etkisini değiştirmedi. L-NAME, gabapentinin MJ yüzdeleri üzerine olan etkisini anlamlı ölçüde iyileştirdi. Ölüm oranları açısından tüm gruplar arasında kontrole göre anlamlı bir farklılık gözlenmedi. Sonuç: Bu çalışma, agmatinin antikonvülzan etkili olabileceğini ve NO aracılı mekanizmaların agmatin ve gabapentinin etkilerinde rolünün olabileceğini ileri sürmektedir.
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