Asetaminofen ile oluşturulan toksik hepatitte rheinin etkileri
Küçük Resim Yok
Tarih
2013
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Trakya Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Asetaminofen hepatotoksisitesinde fizyolojik yolakların ve antioksidan savunma sisteminin yetmezliği sonucu toksik metabolit N-asetil-p-benzoquinone imine'nin karaciğer hasarını ba?lattığı, artan toksik oksijen radikallerinin hücre organellerini bozarak lipid peroksidasyonuna neden olduğu ileri sürülmektedir. Hücrede malondialdehit gibi zararlı oksijen radikalleri birikmekte, glutatyon, glutatyon peroksidaz, katalaz ve süperoksit dismutaz gibi antioksidan enzim aktivitesi önce artmakta sonra yetersiz kalmaktadır. Asetaminofen hepatotoksisitesinde rutinde antioksidan etkili olduğu ileri sürülen N-asetilsistein kullanılmakla birlikte benzer etkinliği dü?ünülen Rhein gibi yeni ajanlar ara?tırılmaktadır. Bu çalı?mada; 8-12 haftalık 10 ratdan olu?an 3 grup olu?turuldu. 1. Grup sağlıklı kontrol olarak kabul edildi. ?ntraperitoneal 1 mL salinden 1 saat sonra plasebo olarak 1 mL %5'lik sodyum karboksi metilsellüloz gavajla verildi. Toksik hepatit grubu olarak tanımlanan 2. Gruba 1 gr/kg asetaminofen 1 mL intraperitoneal verildikten 1 saat sonra gavajla 1 mL %5 sodyum karboksi metilsellüloz verildi. Rheinle tedavisi verilen 3. Gruba 1 gr/kg ılık asetaminofen çözeltisi 1 mL intraperitoneal verildikten 1 saat sonra gavaj yoluyla %5 sodyum karboksi metilsellüloz içinde çözülmü? 1 mL 40mg/kg Rhein verildi. Bütün gruplar 24 saat sonunda sakrifiye edilerek karaciğer ve kan örnekleri alındı. Çalı?mada toksik hepatit grubu ile Rheinli tedavi grubu alanin aminotransferaz, aspartat aminotransferaz, alkalen fosfataz düzeyleri kontrol grubuna göre yüksek ve istatistiksel olarak anlamlı tespit edilmi?tir. Rheinli tedavi grubu gama glutamiltranspeptidaz düzeyleri hariç alanin aminotransferaz, aspartat aminotransferaz, alkalen fosfataz, total bilirubin, direkt bilirubin düzeyleri toksik hepatit grubuna göre istatistiksel olarak 40 anlamlı dü?ük bulundu. Çalı?mada oksidatif stres ürünü olan malondialdehit: toksik hepatit grubunda kontrol grubuna göre az artmı? ancak istatistiksel olarak anlamlı bulunmadı. Artan oksidatif streste azalması beklenen glutatyon düzeyleri toksik hepatit grubunda yüksek bulundu. Bu yüksekliğin nedeninin hasara kar?ı artmı? karaciğer savunması olduğu dü?ünülmektedir. Bu bulgular bize; karaciğer dokusunda beklenen malondialdehit artı?ını ve glutatyon azalmasının tespit edilemediğini, antioksidan tanımlı Rhein (40 mg/kg/intraperitoneal) tedavisi ile hafif artmı? olan malondialdehit düzeyleri deği?memekle birlikte transaminaz düzeylerinde azalma gözlendiğini göstermi?tir. ?leride yapılması planlanan deneysel hepatotoksisite ve antioksidan tedavi çalı?malarında değerlendirilmelerin 24-48 ve 72 saatlik farklı gruplarda ve histopatoloji ile doğrulanarak yapılması yararlı olacaktır. Anahtar kelimeler: Rhein, rat, oksidatif stres, asetaminofen, toksik hepatit
In acetaminophen-induced hepatotoxicity, it is believed that N-asetil-p-benzoquinone imine, a toxic metabolite, causes hepatic damage as a result of failure of physiological pathways and anti-oxidant defense system. Also, it is hypothesised that increased toxic oxygen radicals leads lipid peroxidation by corrupting cell organelles. In cell, noxious oxygen radicals such as malondialdehyde are accumulated and, anti-oxidant enzyme activities such as glutathione, glutathione peroxidase, catalase and superoxide dismutase first increase then fall short. In acetaminophen-induced hepatotoxicity, routinely, N-acetylcystein which have asserted anti-oxidant effects is used. Also, new agents such as rhein which have similar antioxidant effects are searched. In this study, 3 groups were formed; each group had 10 rats which are 8-12 weeks old. Group 1 was claimed as healthy control group. One hour after intraperitoneally administered 1 mL saline, placebo, 1 mL of 5% sodium carboxymetylcellulose, was given by gavage. Group 2 was claimed as toxic hepatitis group. One hour after 1 mL of 1 gr/kg acetaminophen solution intraperitoneally, 1 mL of 5% sodium carboxymetylcellulose was given by gavage. Group 3 was recieving Rhein. One hour after 1 mL of 1 gr/kg acetaminophen solution intraperitoneally, 1 mL of Rhein which was dissolved into %5 sodium carboxymetylcellulose was given by gavage. All rats were sacrificed after 24 hours and, liver and blood samples were collected.42 Alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels of toxic hepatitis and rhein-treated groups were higher than control group and it was statistically significant. In rhein-treated group, except gamma-glutamyl transpeptidase levels, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin and direct bilirubin levels were lower than toxic hepatitis group and it was statistically significant. In the study, malondialdehyde, the product of oxidative stress, was a little higher in toxic hepatitis group than control group. However, that was not statistically significant. In increased oxidative stress, glutathione level is expected to fall but it was elevated in toxic hepatitis group. It is thought that reason to this elevation might be due to increased hepatic defense against liver damage. These findings suggested that expected elevation in malondialdehyde level and reduction in glutathione level cannot be identified. Also, a little elevated malondialdehyde level which was caused by anti-oxidant-defined rhein treatment (40 mg/kg/intraperitoneally) did not change. However, it is showed that reduction in transaminase level was observed. The further experimental hepatotoxicity and anti-oxidant treatment studies are needed. In these further studies, to get more accurate results, the evaluations need to be done in 24, 48 and 72 h groups and the findings need to be verified by histopatological studies. Keywords: rhein, rat, oxidative stress, acetaminophen, toxic hepatitis
In acetaminophen-induced hepatotoxicity, it is believed that N-asetil-p-benzoquinone imine, a toxic metabolite, causes hepatic damage as a result of failure of physiological pathways and anti-oxidant defense system. Also, it is hypothesised that increased toxic oxygen radicals leads lipid peroxidation by corrupting cell organelles. In cell, noxious oxygen radicals such as malondialdehyde are accumulated and, anti-oxidant enzyme activities such as glutathione, glutathione peroxidase, catalase and superoxide dismutase first increase then fall short. In acetaminophen-induced hepatotoxicity, routinely, N-acetylcystein which have asserted anti-oxidant effects is used. Also, new agents such as rhein which have similar antioxidant effects are searched. In this study, 3 groups were formed; each group had 10 rats which are 8-12 weeks old. Group 1 was claimed as healthy control group. One hour after intraperitoneally administered 1 mL saline, placebo, 1 mL of 5% sodium carboxymetylcellulose, was given by gavage. Group 2 was claimed as toxic hepatitis group. One hour after 1 mL of 1 gr/kg acetaminophen solution intraperitoneally, 1 mL of 5% sodium carboxymetylcellulose was given by gavage. Group 3 was recieving Rhein. One hour after 1 mL of 1 gr/kg acetaminophen solution intraperitoneally, 1 mL of Rhein which was dissolved into %5 sodium carboxymetylcellulose was given by gavage. All rats were sacrificed after 24 hours and, liver and blood samples were collected.42 Alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels of toxic hepatitis and rhein-treated groups were higher than control group and it was statistically significant. In rhein-treated group, except gamma-glutamyl transpeptidase levels, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin and direct bilirubin levels were lower than toxic hepatitis group and it was statistically significant. In the study, malondialdehyde, the product of oxidative stress, was a little higher in toxic hepatitis group than control group. However, that was not statistically significant. In increased oxidative stress, glutathione level is expected to fall but it was elevated in toxic hepatitis group. It is thought that reason to this elevation might be due to increased hepatic defense against liver damage. These findings suggested that expected elevation in malondialdehyde level and reduction in glutathione level cannot be identified. Also, a little elevated malondialdehyde level which was caused by anti-oxidant-defined rhein treatment (40 mg/kg/intraperitoneally) did not change. However, it is showed that reduction in transaminase level was observed. The further experimental hepatotoxicity and anti-oxidant treatment studies are needed. In these further studies, to get more accurate results, the evaluations need to be done in 24, 48 and 72 h groups and the findings need to be verified by histopatological studies. Keywords: rhein, rat, oxidative stress, acetaminophen, toxic hepatitis
Açıklama
Tıpta Uzmanlık
Anahtar Kelimeler
Gastroenteroloji, Gastroenterology
