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Objective: Cancer is the most common cause of death after cardiovascular diseases. Cisplatin used in most types of cancer produces neurotoxicity. In this study, we aimed to investigate the effects of pomegranate peel extract (1) in different doses, as potent antioxidants, on the prevention of neurotoxicity due to cisplatin, which is frequently used in cancer treatment.Methods: In our study, newborn rat cortex was used. 2 hours following the application of PPE at 200, 300 and 400 mg/mL, neurotoxicity was established by applying cisplatin in 50 and 100 µM concentrations.Results: In our study, cisplatin decreased cell viability in increasing doses, while PPE showed the best neuroprotective effect in high doses. Increased total oxidant capacity due to toxicity was significantly improved by PPE4. The antioxidant capacity decreased in the toxicity group showed improvement with the administration of PPE4. At the same time, increased TNF-α mRNA expression after cisplatin administration was significantly reduced with the administration of PPE4. The increased caspase 3 (CAS 3) and caspase 9 (CAS 9) mRNA expression due to cisplatin showed improvement with the administration of PPE4. Conclusion:These results indicated that PPE could inhibit cisplatin-induced neurotoxicity, and these effects may be related to anti-apoptotic and antioxidants activities.

Oxaceprol is well-defined therapeutic agent as an atypical inhibitor of inflammation in osteoarthritis. In the present study, we aimed to develop and characterize oxaceprol-loaded poly-lactide-co-glycolide (PLGA) nanoparticles for intra-articular administration in osteoarthritis. PLGA nanoparticles were prepared by doubleemulsion solvent evaporation method. Meanwhile, a straightforward and generally applicable high performance liquid chromatography method was developed, and validated for the first time for the quantification of oxaceprol. To examine the drug carrying capacity of nanoparticles, varying amount of oxaceprol was entrapped into a constant amount of polymer matrix. Moreover, the efficacy of drug amount on nanoparticle characteristics such as particle size, zeta potential, morphology, drug entrapment, and in vitro drug release was investigated. Nanoparticle sizes were between 229 and 509 nm for different amount of oxaceprol with spherical smooth morphology. Encapsulation efficiency ranged between 39.73 and 63.83% by decreasing oxaceprol amount. The results of Fourier transform infrared and DSC showed absence of interaction between oxaceprol and PLGA. The in vitro drug release from these nanoparticles showed a sustained release of oxaceprol over 30 days. According to cell culture studies, oxaceprol-loaded nanoparticles had no cytotoxicity with high biocompatibility. This study was the first step of developing an intra-articular system in the treatment of osteoarthritis for the controlled release of oxaceprol. Our findings showed that these nanoparticles can be beneficial for an effective treatment of osteoarthritis avoiding side effects associated with oral administration. K E Y W O R D Sintra-articular injection, nanoparticle, osteoarthritis, oxaceprol, PLGA

Araştırma Makalesi / Research Article Öz. Amaç: Güçlü bir antioksidan etkiye sahip olan nar kabuğunun pek çok fizyolojik özellikleri gösterilmiştir. Çalışmamızda eksitatör bir nörotransmitter olan glutamatın nörotoksik etkisine karşı, güçlü antioksidan olan nar kabuğunun etkilerini araştırmayı amaçladık. Materyal ve Metot: Çalışmamızda yeni doğan sıçan beyin korteksi kullanılmıştır. Nar kabuğu ekstresi 200, 300 ve 400 mg/ml dozunda uygulandıktan 2 saat sonra 6x10-3 ve 3x10-3 M konsantrasyonda glutamat uygulaması gerçekleştirildi. Toksisite oluşturulduktan 24 saat sonra canlılık testi, total oksidan ve antioksidan kapasite ölçümleri gerçekleştirildi. Bulgular: Glutamat uygulaması artan dozlarda hücre canlılığını önemli ölçüde azaltırken nar kabuğu ekstresi yüksek dozda en iyi nöroprotektif etkiyi ortaya koymuştur. Toksisiteye bağlı artan oksidan kapasite nar kabuğu uygulaması ile anlamlı derecede düzelmiştir. Glutamata bağlı azalan antioksidan kapasite nar kabuğu ekstresi ile düzelme göstermiştir. Nar kabuğu ekstresi tek başına yüksek doz uygulandığında proliferatif etki ortaya koymuştur. Nar kabuğu nöroprotektif etkilerini proinflamatuar sitokin olan tümör nekrozis faktör-α ve apoptotik proteinler olan caspas 3 ve 9 ekspresyonunu baskılayarak ortaya koymuştur. Sonuç: Nar kabuğu ekstresi antioksidan, antiinflamatuar ve anti-apoptotik etkisi ile glutamata bağlı gelişen nörotoksisiteyi önlemiştir.

Aim: The combination of chemotherapeutics and pomegranate peel extract has been shown to have a stronger anti-cancer effect. However, there is no information about how pomegranate peel extract will affect the neurotoxicity that may develop due to cancer chemotherapy. In this study, we aimed to the effects of strong antioxidant pomegranate peel extract on paclitaxel induced primary neuron damage in newborn rats by biochemical and molecular analysis. Material and Method: Paclitaxel toxicity was induced in the primary neuron cell culture derived from newborn rats. PPE 200, 300 and 400 mg/ml doses were applied 2 hours before the paclitaxel for protective effect. Results: In the MTT analysis, paclitaxel reduced cell viability by caused neuronal damage at the end of 24 hours. PPE has demonstrated significant protective effect on cell viability by preventing paclitaxel toxicity at all doses. PPE was demonstrated its effects by reducing oxidative stress, increasing antioxidant capacity, and also by suppressing the TNF-α expression which is pro-inflammatory cytokine, and caspase 9 and 3 expression which are apoptotic proteins. Conclusion: PPE prevents primary neuron damage caused paclitaxel by its antioxidant, anti-inflammatory and anti-apoptotic effect.

Dyer’s kermes (Kermes vermilio) is found only on the kermes oak (Quercus coccifera L). They were used in the past for the preparation of dyes for textiles and as a pharmaceutical. The main constituents of this insect are kermesic acid (ka) and flavokermesic acid (fk). Historically and culturally important dyer’s kermes insect red dyes were investigated by high performance liquid chromatography. Kermes in the Northwest of Turkey were analyzed first time the relative amount of the dyestuffs although their presence has been reported analytical works related to this insect. The relative amount in the acid hydrolyzed extract of Kermes vermilio from the Northwest of Turkey looked very similar to the France.

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