Tesis

Efek α-mangostin terhadap produk peroksidasi lipid 4-HNE dan kadar TNF-α dan IL-6 di jaringan hepar tikus model resistensi insulin = The effect of α-mangostin on 4-HNE lipid peroxidation product and TNF-α dan IL-6 in the liver of insulin resistance rat model.

Latar belakang: Penelitian ini bertujuan mengevaluasi efek α-mangostin (α-MG) terhadap 4-hidroksinonenal (4-HNE) dan sitokin proinflamasi (TNF-α dan IL-6) di jaringan hepar resistensi insulin. Metode: Tikus Wistar dibagi menjadi 6 kelompok yaitu kelompok 1 -6. Pada minggu 1-3, kelompok 1 dan 2 diberi pakan normal dan minum aquades. Kelompok 3-6 diberi high fat diet (HFD), karbohidrat, dan minum glukosa kemudian dikonfirmasi resistensi insulinnya dengan HOMA-IR >2,0. Pada minggu 4-11 kelompok 1 tidak diberi perlakuan apapun sebagai kelompok normal, kelompok 2 diberi α-MG 200 mg/kgBB, kelompok 3 tidak diberi terapi apapun, kelompok 4-6 diberi metformin 200 mg/kgBB, α-MG 100 mg/kgBB, dan α-MG 200 mg/kgBB. Seluruh tikus dinekropsi pada minggu ke-11 kemudian diambil jaringan heparnya. Kadar lipid dianalisis dengan lipid extraction and quantification kit. Ekspresi 4-HNE dianalisis dengan teknik imunohistokimia (IHK). Kadar TNF-α dan IL-6 diperiksa dengan ELISA. Hasil: Pemberian α-MG dosis 100 mg/kgBB dan 200 mg/kgBB di jaringan hepar tikus resistensi insulin tidak menurunkan kadar lipid (p > 0,05), secara kualitatif menurunkan ekspresi 4-HNE, menurunkan kadar TNF-α secara signifikan baik pada dosis 100 mg/kgBB (p=0,049) maupun dosis 200 mg/kgBB (p=0,015), serta tidak menurunkan kadar IL-6 (p > 0,05), ketika dibandingkan dengan Metformin. Kesimpulan: Di jaringan hepar tikus resistensi insulin, pemberian α-MG dosis 100 mg/kgBB dan 200 mg/kgBB mampu menurunkan kadar TNF-α dan ekspresi 4-HNE, tetapi tidak menurunkan kadar lipid intrahepatik dan IL-6.
Kata kunci: α-mangostin; inflamasi; resisten insulin; stres oksidatif



Background: This study aimed to evaluate the effect of α-mangostin (α-MG) on 4-hydroxynonenal (4-HNE) and proinflammatory cytokines (TNF-α and IL-6) in insulin-resistant liver tissue. Methods: Wistar rats were divided into 6 groups, namely groups 1 -6. At weeks 1 -3, groups 1 and 2 were given normal feed and drank aquadest. Groups 3-6 were given a high fat diet (HFD), carbohydrates, and drinking glucose then confirmed their insulin resistance with HOMA-IR >2.0. At week 4-11 group 1 was not given any treatment as normal group, group 2 was given α-MG 200 mg/kgBW, group 3 was not given any therapy, group 4-6 was given metformin 200 mg/kgBW, α-MG 100 mg/kgBW, and α-MG 200 mg/kgBW. All rats were necropsied at week 11 and then the liver tissue was taken. Lipid levels were analyzed by lipid extraction and quantification kit. Expression of 4- HNE was analyzed by immunohistochemical (CPI) technique. TNF-α and IL-6 levels were checked by ELISA. Results: Administration of α-MG doses of 100 mg/kgBW and 200 mg/kgBW in liver tissue of insulin-resistant rats did not reduce lipid levels (p > 0.05), qualitatively decreased 4-HNE expression, significantly reduced TNF-α levels at a dose of 100 mg/kgBW (p=0.049) and at a dose of 200 mg/kgBW (p=0.015), and did not reduce IL-6 levels (p > 0.05), when compared with Metformin. Conclusion: In the liver tissue of insulin resistant rats, administration of α-MG doses of 100 mg/kgBW and 200 mg/kgBW was able to reduce TNF-α levels and 4-HNE expression, but did not reduce intrahepatic lipid and IL-6 levels.
Keywords: α-mangostin; inflammation; insulin resistance; oxidative stress