The Effects of Riluzole on Cisplatin-induced Ototoxicity

Introduction Riluzole (2-amino-6-trifluoromethoxy benzothiazole) is known as a neuroprotective, antioxidant, antiapoptotic agent. It may have beneficial effects on neuronal cell death due to cisplatin-induced ototoxicity. Objective To evaluate the effect of riluzole on cisplatin-induced ototoxicity in Guinea pigs. Methods Twenty-four Guinea pigs, studied in three groups, underwent auditory brainstem response evaluation using click and 8 kHz tone burst stimuli. Subsequently, 5 mg/kg of cisplatin were administered to all animals for 3 days intraperitoneally (i.p.) to induce ototoxicity. Half an hour prior to cisplatin, groups 1, 2 and 3 received 2 ml of saline i.p., 6 mg/kg of riluzole hydrochloride i.p., and 8 mg/kg of riluzole hydrochloride i.p., respectively, for 3 days. The auditory brainstem responses were repeated 24 hours after the last drug administration. The cochleae were analyzed by transmission electron microscopy (TEM). Results After drug administiration, for 8,000 Hz stimulus, group 1 had significantly higher threshold shifts when compared with groups 2 (p 0.05). Transmission electron microscopy findings demonstrated the protective effect of riluzole on the hair cells and the stria vascularis, especially in the group treated with 8 mg/kg of riluzole hydrochloride. Conclusion We can say that riluzole may have a protective effect on cisplatin- induced ototoxicity. However, additional studies are needed to confirm these results and the mechanisms of action of riluzole. Copyright © 2019 by Thieme Revinter Publicações Ltda, Rio de Janeiro, Brazi

Neuroprotective role of delta opioid receptors in hypoxic preconditioning

Background/aim: The purpose of the present study was to explore the neuroprotective role of delta opioid receptors (DOR) in the rat cortex in hypoxic preconditioning. Materials and methods: Rats were randomly divided into 8 groups: control (C), sham (5), hypoxic preconditioning (PC), severe hypoxia (SH), PC + SH, PC + SH + Saline (PS), PC + SH + DPDPE (DPDPE, selective DOR agonise), PC + SH + NT (NT, Naltrindole, selective DOR antagonist). Drugs were administered intracerebroventrically. Twenty four h after the end of 3 consecutive days of PC (10\% O-2 , 2 h/day), the rats were subjected to severe hypoxia (7\% O-2 for 3 h). Bcl-2 and cyt-c were measured by western blot, and caspase-3 was observed immunohistochemically. Results: Bcl-2 expressions in the PC group were higher than in control, SH, and PC + SH groups. Even though there were no significant differences between the groups in terms of cyt-c levels, caspase-3 immunoreactivity of cortical neurons and glial cells in the severe hypoxia and NT groups were higher than in the control, sham, and hypoxic preconditioning groups. DPDPE administration diminished caspase-3 immunoreactivity compared with all of the severe hypoxia groups. Conclusions: These results suggest that cortical cells are resistant to apoptosis via increased expression of Bcl-2 and decreased immunoreactivity of caspase-3 in the cortex, and that DOR is involved in neuroprotection induced by hypoxic preconditioning via the caspase-3 pathway in cortical neurons

Is leptin receptor expression triggered in the case of embryo transfer to endometrium coculture?

Background/aim: A synchronized dialogue between maternal and embryonic tissues is required for successful implantation. Low uterine receptivity is responsible for two-thirds of implantation failures and leptin is effective in the physiology of reproduction by binding to specific receptors. In this study, we investigateleptin receptor expression in cases of embryo transfer to endometrial coculture. Materials and methods: Biopsy materials were taken from 20 females with indication for coculture application and were cultured in an appropriate medium after the epithelial cells were isolated. The grown cells were cultured in chamber slides as the first group. For the second group, day 3 embryo was added to chamber slides and the development was observed. The embryo was transferred 1 or 2 days later and other cells (after the transfer process) were used to form the second group. After fixation, immunohistochemical staining was performed with anti-leptin primary antibody. Results: Regarding the coculture without embryo transfer, moderate leptin receptor immunoreactivity was seen in the perinuclear region and the cell membrane. Also, regarding the coculture with embryo transfer, moderate leptin receptor immunoreactivity was seen in the cytoplasm and strong leptin receptor immunoreactivity was seen in the cell membrane. Conclusion: Embryo transfer to endometrium coculture triggers leptin receptor expressio

Could nephrotoxicity due to colistin be ameliorated with the use of N-acetylcysteine?

WOS: 000286194400017PubMed ID: 20845026The protective effect of N-acetylcysteine (NAC) on nephrotoxicity due to contrast nephropathy and reperfusion-induced ischemia has been reported in experimental models. However, its efficacy on colistin-induced nephrotoxicity has not been elucidated yet. The primary aim of this study was to evaluate the nephrotoxic effect of colistin and to investigate the possible protective effect of NAC on colistin-induced nephrotoxicity. The secondary aim was to research the systemic effects of nephrotoxicity-induced oxidative stress on the lung. Eighteen female Sprague-Dawley rats were randomly assigned and were given (a) 1 ml/kg sterile saline, (b) 300,000 IU/kg/day colistin, and (c) 300,000 IU/kg/day colistin and 150 mg/kg NAC for six consecutive days. Plasma blood urea nitrogen (BUN), creatinine, urinary creatinine, urinary protein, plasma TNF-alpha levels, renal tissue superoxide dismutase (SOD) and malondialdehyde (MDA) activity and immunocytochemical findings were evaluated. Colistin exerted nephrotoxicity and achieved a significant increase in plasma BUN and creatinine levels and renal tissue SOD levels. NAC exhibited no significant effect on biochemical parameters but reduced renal tissue SOD level and reversed immunocytochemical staining of inducible nitric oxide synthase (i-NOS) and neurotrophin-3. Increased oxidative stress in the lung tissue of the rats treated with colistin has also been documented. Additionally, NAC significantly reduced the immunostaining of endothelial NOS (e-NOS) and i-NOS in the lung tissue. Colistin-induced renal toxicity may be attributable to oxidative damage. The combined treatment of colistin plus NAC seems to have a beneficial role in restoration of the oxidant injury which may be related to its antioxidant effect.Internal Medicine Postgraduate Education Society (IMSED)The authors do not have any personal relationships to disclose which may affect the present work. The study was supported by a grant from the Internal Medicine Postgraduate Education Society (IMSED)

Is leptin receptor expression triggered in the case of embryo transfer to endometrium coculture?

Background/aim: A synchronized dialogue between maternal and embryonic tissues is required for successful implantation. Low uterine receptivity is responsible for two-thirds of implantation failures and leptin is effective in the physiology of reproduction by binding to specific receptors. In this study, we investigate leptin receptor expression in cases of embryo transfer to endometrial coculture. Materials and methods: Biopsy materials were taken from 20 females with indication for coculture application and were cultured in an appropriate medium after the epithelial cells were isolated. The grown cells were cultured in chamber slides as the first group. For the second group, day 3 embryo was added to chamber slides and the development was observed. The embryo was transferred 1 or 2 days later and other cells (after the transfer process) were used to form the second group. After fixation, immunohistochemical staining was performed with anti-leptin primary antibody. Results: Regarding the coculture without embryo transfer, moderate leptin receptor immunoreactivity was seen in the perinuclear region and the cell membrane. Also, regarding the coculture with embryo transfer, moderate leptin receptor immunoreactivity was seen in the cytoplasm and strong leptin receptor immunoreactivity was seen in the cell membrane. Conclusion: Embryo transfer to endometrium coculture triggers leptin receptor expression

Sisplatin ile İndüklenmiş Uterus Toksisitesinde Asetil L-Karnitinin Koruyucu Etkisinin Araştırılması

Objective: The aim of the study was to investigate the prophylactic effects of acetyl L-carnitine against to uterus induced by cisplatin. Methods: Twenty-four female Wistar albino rats were divided into four groups: group I (control) was administered with saline; group II was administered with acetyl L-carnitine; group III was administered with cisplatin; group IV was pretreated with acetyl L-carnitine before cisplatin intraperitoneal injection. After 72h of cisplatin injection uterine tissue was removed. Histological and immunohistochemical investigations were performed, respectively. Results: We found that the number of TUNEL and caspases positive cells were increased in the endometrial epithelium, subepithelial connective tissue, endometrial glands and stroma in group III compare to the other groups. Furthermore inflammation and edema were observed in uterus of rats in group III. Conclusion: We can concluded that pretreatment of acetyl L-carnitine administration has protective effect on histological alteration of uterus caused by cisplatin.Amaç: Bu çalışmanın amacı, asetil L-karnitinin, sisplatinin neden olduğu uterus hasarına karşı profilaktik etkilerini araştırmaktır. Yöntem: Yirmi dört adet Wistar albino cinsi dişi sıçanlar dört gruba ayrıldı: 1. gruba (kontrol) salin uygulaması yapıldı; 2. gruba asetil L-karnitin uygulaması yapıldı; 3. gruba sisplatin uygulaması yapıldı; 4. grup ise sisplatinin intraperitoneal enjeksiyonu öncesinde asetil L-karnitin ile ön tedaviye tabi tutuldu. Sisplatin enjeksiyonundan 72 saat sonra uterus dokusu çıkarıldı. Histolojik ve immünohistokimyasal incelemeler yapıldı. Bulgular: TUNEL ve kaspaz pozitif hücre sayılarının, diğer gruplara göre 3. grupta endometriyal epitelde, subepitelyal bağ dokusunda, endometriyal bezlerde ve stromada arttığını bulduk. Ayrıca 3. Gruptaki ratların uterusunda inflamasyon ve ödem gözlenmiştir. Sonuç: Asetil L-karnitin ön tedavi uygulamasının, sisplatin kaynaklı uterus histolojisinin değişikliği üzerinde koruyucu etkisi olduğu sonucuna vardık

Investigation of the Protective Effects of Acetyl L-Carnitine on Cisplatin-Induced Uterus Toxicity

Objective: The aim of the study was to investigate the prophylactic effects of acetyl L-carnitine against to uterus induced by cisplatin. Methods: Twenty-four female Wistar albino rats were divided into four groups: group I (control) was administered with saline; group II was administered with acetyl L-carnitine; group III was administered with cisplatin; group IV was pretreated with acetyl L-carnitine before cisplatin intraperitoneal injection. After 72h of cisplatin injection uterine tissue was removed. Histological and immunohistochemical investigations were performed, respectively. Results: We found that the number of TUNEL and caspases positive cells were increased in the endometrial epithelium, subepithelial connective tissue, endometrial glands and stroma in group III compare to the other groups. Furthermore inflammation and edema were observed in uterus of rats in group III. Conclusion: We can concluded that pretreatment of acetyl L-carnitine administration has protective effect on histological alteration of uterus caused by cisplatin