The role of resveratrol in hepatotoxicity caused by methotrexate

Abstract

Methotrexate is an immunosuppressive and antineoplastic drug that may induce hepatotoxicity. Resveratrol is a compound that has a protective effect thanks to its antioxidant role. In present study was aimed to investigate posibble protective effects of resveratrol in methotrexate induced hepatotoxicity. Eighteen Wistar Albino rats were equally divided into three groups: Control, Methotrexate, Methotrexate + Resveratrol. After a single dose of methotrexate (15 mg/kg, i.p.), resveratrol (10 mg/kg, orally) was applied for 7 days. Fallowing 7 days, rats were sacrificed. Histopathological (H-E staining), immunohistochemical (Tumor Necrosis Factor Alpha, inducible Nitric Oxide Synthases, Nuclear Factor Kappa) and biochemical (Total Oxidant Status, Total antioxidants Status and Oxidative Stress Index) analyses were assayed in liver tissue samples. Additionally, Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase and Total Biluribin activities were assayed in serum samples for biochemical analyses. Normal liver tissues were observed in control groups. Histopatholocigal changes, high staining of Tumor Necrosis Factor Alpha, inducible Nitric Oxide Synthases, Nuclear Factor Kappa, increasing levels of tissue Total Oxidant Status, Oxidative Stress Index and decreasing levels of tissue Total antioxidants Status were observed in methotrexate groups. Moreover, Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase and Total Biluribin levels increased in methotrexate groups too (p<0.05). However, these findings were lower in the Methotrexate + Resveratrol groups (p<0.05). In this study were observed that oxidant levels could increase after methotrexate applied in the liver, whereas resveratrol alleviated effects of hepatotoxicity by histopathological, immunohistochemical and biochemical analyses.

Whey protein concentrate ameliorates the methotrexate-induced liver and kidney damage

“…showed that MTX-induced liver, kidney and heart damage was ameliorated with a flavonoid derivative diosmin (47) . Similar to these studies, there are studies in which vitamin C (7) , resveratrol (44) , quercetin (45) , berberine (48) and gallic acid (43) were used to treat MTX-induced tissue damage. In this study, whey proteins, which are known to have antioxidant properties, ameliorated MTX-induced oxidative damage by decreasing MDA level and increasing GSH level, SOD and GST activities.…”

“…Since MTX induces oxidative stress by increasing reactive oxygen species in tissues (38,40,43) , the effects of various antioxidant substances against MTX-induced oxidative stress have been investigated (7,38,(43)(44)(45) .…”

Investigation of the Effects of Bilberry Extract on Methotrexate-Induced Hepatotoxicity

“…Başka çalışmalarda da farklı doz ve sürelerde Mtx uygulamasının doku MDA düzeylerinde artışa yol açtığı gösterilmiştir (22,(25)(26)(27). Ayrıca Mtx karaciğer dokusunda oksidatif stres göstergelerinden olan TOS'ta da artışa neden olabilir (19,28). Çalışmamızda da MtxG'nin MDA ve istatistiksel anlamlı olmasa da TOS seviyelerinde literatürle uyumlu artış mevcuttu.…”

“…Mtx metaboliti olan Mtx-poliglutamatlar (Mtx-PGs), oksidan seviyelerini artırmalarının yanında, antioksidanları da baskılayarak karaciğer dokusunda oksidatif stresi indükleyebilir (29). Mtx uygulamasının; SOD, CAT ve GPx gibi antioksidan enzimlerde ve GSH'de azalmaya yol açtığı farklı çalışmalarda gösterilmiştir (27,30) İlave olarak Mtx TAS'ta da azalmaya neden olabilir (28). Biz de çalışmamızda literatürle uyumlu olarak MtxG'deki TAS, CAT ve SOD düzeylerinde, istatistiksel olarak anlamlı olmamakla birlikte bir düşüş saptadık.…”