Özden BORAL, Deniz Gözde ÇELİK, Halim İŞSEVER

VİSERAL LAYŞMANYAZ MODELİ OLUŞTURULAN FARELERDE TİGESİKLİN VE REİSHİ SHİİTAKE MAİTAKE MANTAR EKSTRESİNİN TEDAVİ ETKİNLİĞİNİN DEĞERLENDİRİLMESİ

Amaç: Viseral layşmanyaz (VL) tropikal ve subtropikal bölgelerde yayılım gösteren, tedavi edilmediğinde ölümcül olabilen bir enfeksiyondur. VL tedavisi kullanılan bazı ilaçlara direnç gelişimi nedeni ile giderek güçleşmektedir. Çalışmamızda Leishmania donovani (ATCC 30030) suşu ile viseral layşmanyaz modeli oluşturulan BALB/c farelerde, tigesiklin (Tig), Reishi-Shiitake-Maitake (RSM) mantar ekstresi ve her iki ilacın birlikte tedavi etkinliğinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Tedavi etkinliğinin karşılaştırılmasında amfoterisin B (AMB) ile tedavi edilen fare grubu kullanılmıştır. BALB/c farelerine (n=40), 100 μL PBS içinde 107 strasyoner fazlı L.donovani promastigotları kuyruğun lateral damarına intravenöz yolla verildi. BALB/c fareler sekizli 5 gruba ayrıldı. Tig grubuna 5 gün intraperitonal yoldan 3.7 mg/kg tigesiklin, RSM grubuna 5 gün oral gavaj ile 10 mg/kg RSM ekstresi, Tig+RSM grubuna aynı yol, gün ve dozlarda tigesiklin ve RSM ekstresi, AMB grubuna 5 gün OG ile 15 mg/kg amfoterisin B verilmiş, kontrol grubuna hiçbir işlem yapılmamıştır. On ikinci günde ketamin ile sedatize edilen farelerin dalak ve karaciğeri alınmıştır. Parazit yükü Leishman Donovan Unit (LDU) ve kantitatif RT-PCR ile belirlenmiştir. Bulgular: Tüm gruplar, LDU ve RT-RCR bulgularına göre istatistiksel olarak değerlendirildiğinde, kontrol grubuna göre en düşük değer AMB grubunda elde edilirken (p<0,001), ikinci en düşük değer Tig+RSM grubunda elde edilmiştir (p<0,001). Tig+RSM grubunda elde edilen değerler AMB grubu hariç olmak üzere diğer gruplardan anlamlı ölçüde düşük bulunmuştur. Sonuç: Çalışma bulgularımız tigesiklin ile birlikte RSM ekstresinin kullanılmasının VL tedavisinde alternatif olabileceğini göstermekle birlikte, farklı doz ve veriliş yollarının denendiği yeni çalışmalarla desteklenmesi gerektiğini düşündürmüştür. Anahtar Kelimeler: Viseral layşmanyaz, tigesiklin, reishi shiitake maitake, tedavi

Anahtar Kelimeler:

Viseral layşmanyaz, Tigesiklin, Reishi Shiitake Maitake, Tedavi

EVALUATION OF THE TREATMENT EFFICACY OF TIGECYCLINE AND REISHI SHIITAKE MAITAKE MUSHROOM EXTRACT IN MICE WITH THE VISCERAL LEISHMANIASIS MODEL

Objective: Visceral leishmaniasis (VL) is an infection that can be fatal if left untreated. Treatment of VL is becoming increasingly difficult due to the development of resistance to some drugs used. We aimed to investigate the efficacy of tigecycline (Tig) and Reishi-Shiitake-Maitake (RSM) mushroom extract alone and in combination in BALB/c mice infected with the Leishmania donovani strain (ATCC 30030). Materials and Methods: To compare the treatment efficacy, the mice that were treated with amphotericin B (AMB) were used as the control group. BALB/c mice (n=40) were intravenously inoculated in the lateral vein of the tail with 107 stationary-phase L. donovani promastigotes in 100 μL of PBS. BALB/c mice were divided into 5 groups of 8. Tig group received 3.7 mg/kg tigecycline intraperitoneally for 5 days, RSM group received 10 mg/ kg RSM extract by oral gavage for 5 days while Tig+RSM group received the same doses of both drugs via the same routes. Also, the AMB group received 15mg/kg amphotericin B by oral gavage for 5 days. The spleen and liver of all mice that were sedated with ketamine were collected on the 12th day. Parasite load was determined by Leishman Donovan Unit (LDU) and quantitative RT-PCR. Results: When all groups were statistically evaluated according to LDU and RT-PCR findings, the lowest value was obtained in the AMB group compared to the value in the control group, while the second lowest value was obtained in the Tig+RSM group. The data obtained in the Tig+ RSM group were significantly lower macrothan the data in other groups, except for the AMB group. Conclusion: Our study suggested that the use of RSM extract together with tigecycline may be an alternative in the treatment of VL. Further studies using different doses and routes of administration are needed to evaluate the efficacy of this combination.

Keywords:

Visceral leishmaniasis, tigecycline, reishi shiitake maitake, treatment,

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