Publication: Erkek Sıçanlarda Deneysel Oluşturulmuş Ürolityazis Modelinde Scolymus Hispanicus L. Ekstratının Etkinliğinin Araştırılması
Abstract
Etnofarmakolojik Alaka Düzeyi: Dünyanın farklı bölgelerinde, çeşitli tıbbi bitkiler pek çok hastalık için geleneksel tıp uygulamaları kapsamında kullanılmaktadır. Bunlardan biri olan scolymus hispanicus l. (şevketibostan), Türkiye'nin özellikle batısında yaygın olarak yetiştirilen ve böbrek taşı hastalığını tedavi amacıyla kullanılmakta olan bir bitkidir. Geçmişte ekstresi 'Lityazol Cemil' adıyla piyasa sürülmüş olmasına rağmen, tedavi etkinliği ile ilgili yeterli bilimsel kanıt bulunmamaktadır. Çalışmanın Amacı: Bu çalışmada şevketibostan kök kabuğu etanolik ekstratının potansiyel anti-ürolitiatik aktivitesini ve güvenliğini değerlendirmek hedeflenmiştir. Gereç ve Yöntem: 245-320 g ağırlığında, 3 aylık erişkin erkek Sprague-Dawley ratlar beş gruba ayrıldı (n=10, grup başına); (i) kontrol (K); (ii) hastalık (H); (iii) tedavi (T); (iv) profilaksi (P); (v) yan etki (Y). Taş oluşumu sağlamak için H, T ve P gruplarına çeşme suyu yerine, %0,75 (v/v) etilen glikol (EG) çözeltisi verildi. T grubuna oral gavajla 100 mg/kg/gün bitki ekstratı 4. haftadan sonra, P ve Y grubuna ise 8 hafta boyunca verildi. Çalışma bitiminde deney hayvanlarından metabolik kafeslerle 24 saatlik idrar örnekleri toplandı ve hayvanlar anestezi altında eksanguinasyon ile sakrifiye edildi. Kan örneklerinden kalsiyum (Ca), fosfor (P), magnezyum (Mg), kreatinin, alanin transaminaz (ALT), aspartat aminotransferaz (AST), alkalen fosfataz (ALP), ürik asit, idrar örneklerinden pH, volüm, dansite, kreatinin, Ca, ürik asit, oksalat (Ox) ve sitrat parametreleri değerlendirildi. Böbrek dokularındaki histopatolojik bulgular skorlandı. Bulgular: Böbrek taşı gruplarında (H, T ve P) histopatolojik kristal skorları P grubunda en düşüktü. Kontrol grubu ve P grubu ile T grubu arasında istatistiksel anlamlı farklılık saptanmadı (p=0.317). T ve P grubunun kristal skorları H grubuna göre daha düşük saptandı (p<0.001). Böbrek taşı gruplarının inflamasyon ve fibrozis skorları K grubuna göre artmıştı (p<0.001). 8 hafta ekstre verilen P grubunun skorları H grubuna göre düşük (p=0.039), 4 hafta ekstre verilen T grubu ile benzerdi (p=0.118). 8 hafta ekstre verilen P ve Y gruplarının serum ürik asit değerleri, ekstre verilmeyen gruplara (K ve H) göre daha düşük saptandı (p=0.014). Serum ALT, ALP parametrelerinde böbrek taşı gruplarında artış gözlendi, tek başına ekstre verilen grupla (Y), K grubunun değerleri benzerdi (p=0.995). Sonuç: Scolymus hispanicus l. kök kabuğu ekstratı, 100 mg/kg/gün dozunda, böbrek taşı hastalığı oluşturulmuş rat modelinde, sistemik toksisiteye yol açmadan, tedavi ve profilaksi etkinliği göstermiştir. Bu çalışmanın histopatolojik sonuçları, bitkinin fitokimyasal içeriğinin başka çalışmalarda in vitro gösterilmiş anti-oksidan etkinliği ile paralel olmasına rağmen, bu etkinliği doğrulayabilecek biyokimyasal belirteçler incelenmemiştir. Laboratuvar bulguları, ekstratın çözücü etkinliği olmadığını gösterse de diüretik ve ekspulsif etkinlik bu çalışma sınırları dahilinde belirsizliğini korumaktadır. Etki mekanizmalarının tam olarak açıklanabilmesi için daha kapsamlı çalışmalara ihtiyaç duyulmaktadır.
Ethnopharmalogical Relevance: In the different regions of the Earth, various medicinal plants are used within the scope of traditional medicine for many diseases. One such plant, scolymus hispanicus l. (common golden thistle), is widely cultivated especially in the western part of Turkey and used for treating kidney stone disease. Although its extract was once marketed under the name 'Lityazol Cemil', there is not enough scientific evidence regarding its effectiveness. Aim of the study: In this study, evaluation of potential antiurolithiatic activity and safety of root bark extract of common golden thistle is targeted. Material and Method: 3 months old adult male Sprague-Dawley rats, each weighing 245-320 grams, were seperated into five groups (n=10 for each group); (i) control (K), (ii) disease (H), (iii) treatment (T), (iv) prophylaxis (P) and (v) side effect (Y). H, T and P groups were given %0.75 (v/v) ethylene glycol (EG) solution instead of tap water to induce stone formation. T group was administered 100 mg/kg/day of plant extract by oral gavage after 4th week while P and Y groups were given for 8 weeks. In the end of the study, 24-hour urine samples were collected from the experimental animals by metabolic cages and the animals were sacrified by exsanguination under anestesia. Calcium (Ca), phosphorus (P), magnesium (Mg), creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), uric acid parameters in blood samples and pH, volume, density, creatinine, Ca, uric acid, Oxalate (Ox) and citrate parameters in urine samples were evaluated. Histopathologic findings in kidney tissues were scored. Results: In the kidney stone groups (H, T and P), histopathological crystal scores were lowest in the P group. There was no statistically significant difference between the control group and P group and T group (p=0.317). The crystal scores of the T and P groups were detected to be lower than the H group (p<0.001). Inflammation and fibrosis scores of kidney stone groups were increased compared to K group (p<0.001). The group P, which received 8 weeks of extract, had lower scores than the group H (p=0.039) and similar to the group T, which received 4 weeks of extract (p=0.118). In the P and Y groups given 8 weeks of extract, serum uric acid values were lower than those of the groups not given extract (K and H) (p=0.014). An increase was observed in serum ALT and ALP parameters in the kidney stone groups, and the values of the extract alone group (Y) and the K group were similar (p=0.995). Conclusion: Root bark extract of scolymus hispanicus l., at a dose of 100 mg/kg/day, showed treatment and prophylaxis efficacy in a rat model of kidney stone disease without causing systemic toxicity. The histopathological results of this study, although parallel to the in vitro antioxidant activity of the plant's phytochemical content demonstrated in other studies, biochemical markers which could confirm this activity were not examined. Although laboratory findings indicate that the extract has no solvent activity, diuretic and expulsive activity remains unclear within the limits of this study. In order to fully explain the mechanisms of impact, more comprehensive studies are needed.
Ethnopharmalogical Relevance: In the different regions of the Earth, various medicinal plants are used within the scope of traditional medicine for many diseases. One such plant, scolymus hispanicus l. (common golden thistle), is widely cultivated especially in the western part of Turkey and used for treating kidney stone disease. Although its extract was once marketed under the name 'Lityazol Cemil', there is not enough scientific evidence regarding its effectiveness. Aim of the study: In this study, evaluation of potential antiurolithiatic activity and safety of root bark extract of common golden thistle is targeted. Material and Method: 3 months old adult male Sprague-Dawley rats, each weighing 245-320 grams, were seperated into five groups (n=10 for each group); (i) control (K), (ii) disease (H), (iii) treatment (T), (iv) prophylaxis (P) and (v) side effect (Y). H, T and P groups were given %0.75 (v/v) ethylene glycol (EG) solution instead of tap water to induce stone formation. T group was administered 100 mg/kg/day of plant extract by oral gavage after 4th week while P and Y groups were given for 8 weeks. In the end of the study, 24-hour urine samples were collected from the experimental animals by metabolic cages and the animals were sacrified by exsanguination under anestesia. Calcium (Ca), phosphorus (P), magnesium (Mg), creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), uric acid parameters in blood samples and pH, volume, density, creatinine, Ca, uric acid, Oxalate (Ox) and citrate parameters in urine samples were evaluated. Histopathologic findings in kidney tissues were scored. Results: In the kidney stone groups (H, T and P), histopathological crystal scores were lowest in the P group. There was no statistically significant difference between the control group and P group and T group (p=0.317). The crystal scores of the T and P groups were detected to be lower than the H group (p<0.001). Inflammation and fibrosis scores of kidney stone groups were increased compared to K group (p<0.001). The group P, which received 8 weeks of extract, had lower scores than the group H (p=0.039) and similar to the group T, which received 4 weeks of extract (p=0.118). In the P and Y groups given 8 weeks of extract, serum uric acid values were lower than those of the groups not given extract (K and H) (p=0.014). An increase was observed in serum ALT and ALP parameters in the kidney stone groups, and the values of the extract alone group (Y) and the K group were similar (p=0.995). Conclusion: Root bark extract of scolymus hispanicus l., at a dose of 100 mg/kg/day, showed treatment and prophylaxis efficacy in a rat model of kidney stone disease without causing systemic toxicity. The histopathological results of this study, although parallel to the in vitro antioxidant activity of the plant's phytochemical content demonstrated in other studies, biochemical markers which could confirm this activity were not examined. Although laboratory findings indicate that the extract has no solvent activity, diuretic and expulsive activity remains unclear within the limits of this study. In order to fully explain the mechanisms of impact, more comprehensive studies are needed.
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