EFEKTIVITAS KOMBINASI DL-αTOKOFEROL DAN ASAM ASKORBAT TERHADAP KADAR LDL-OX, sCD36, sVCAM-1 DAN NO PADA ANAK SINDROM NEFROTIK

Abstract

Latar Belakang: Stres oksidatif, disfungsi endotel dan inflamasi mendasari proses aterosklerosis pada anak sindrom nefrotik (SN). Kombinasi dl-α-tokoferol dan asam askorbat berpotensi menurunkan proses stress oksidatif dan disfungsi endotel banyak diteliti pada orang dewasa namun terbatas pada anak SN. Tujuan: Membuktikan pengaruh pemberian kombinasi dl-α-tokoferol dan asam askorbat terhadap Δ kadar LDL-ox sebagai marker stress oksidatif, reseptor makrofag sCD36, sVCAM-1 dan NO sebagai biomarker disfungsi endotel pada anak SN usia 1 – 15 tahun. Metode: Randomized pre test-post test control group design dilakukan pada anak SN usia 1- 15 tahun selama 12 minggu. Kelompok perlakuan diberi obat standar (prednison dosis penuh) dan kombinasi dl-α-tokoferol 10-15 mg /kg/hari & asam askorbat dengan dosis sama, dibagi 2 dosis secara oral. Kelompok kontrol menerima obat standar dan plasebo. Variabel LDL-ox, sCD36, sVCAM-1 diperiksa secara ELISA, NO secara kolorimetri. Analisis statistik digunakan uji Wilcoxon, uji t tidak berpasangan/Mann-Whitney U. Hasil: Rerata pretest-posttest kelompok perlakuan kadar LDL-ox (127,2 menjadi 89,5 U/L); sVCAM-1:(929,4 menjadi 868,4ng/mL); NO: (8,9 menjadi 8,5μM/L) menurun. Kadar sCD36 (72,5 menjadi 123,5 ng/mL) meningkat. Kelompok kontrol: LDL-ox (125,2 menjadi 76,7 U/L), sVCAM-1(1231,2 menjadi 1008,0 ng/mL), NO (8,2 menjadi 7,9μM) menurun,. sCD36(56,9 menjadi 61,7ng/mL) meningkat. Uji Wilcoxon kelompok perlakuan dan kontrol berturut-turut kadar LDL-ox p =0,039 dan 0,001, kadar sCD36 : p=0,163 & 0,088, sVCAM-1: p=0,306 & 0,122 dan NO: p=0,983 & 0,760. Δ LDL-ox -37.7 vs - 48.6U / L ; Δ sCD36: 51.1vs 17,2ng / mL; Δ sVCAM-1: -61.0 vs –223ng /mL ; ΔNO -0.4 vs- 0.6 mg/dL dengan uji beda berturut-turut p = 0,594; 0,327; 0,883; 0,864. Berdasarkan status remisi, uji beda kadar LDL-ox, Δ kadar LDL-ox dan kadar sVCAM-1 post test pada kelompok perlakuan berbeda bermakna dengan p=0,016; 0,047 dan 0,000. Kesimpulan: Pemberian kombinasi dl-α-tokoferol dan asam askorbat dosis 10-15 mg/kgBB/hari selama 12 minggu efektif menurunkan kadar stres oksidatif dan disfungsi endotel pada kelompok perlakuan yang remisi, tetapi tidak efektif terhadap Δ kadar LDL-ox, Δ sCD36, Δ sVCAM-1 dan Δ NO di antara dua kelompok. Kata kunci: Sindrom nefrotik, anti oksidan, stress oksidatif, disfungsi endotel Background: Oxidative stress, endothelial dysfunction and inflammation contribute to early atherosclerosis process in neprotic syndrome (NS). Administration of combination dl-α-tocopherol and ascorbic acid are potential in decreasing oxidative stress and endothelial dysfunction, investigated in adult but not yet in children. Objective: To prove that combined supplementation of dl-α-tocopherol and ascorbic acid on serum levels of oxidized LDL (ox-LDL), soluble scavenger receptor of macrophage CD36(sCD36), soluble vascular cellular adhesion molecule (sVCAM-1) and nitric oxide (NO) level in NS of 1- 15 years old. Methods: A randomized pre test–post test control group design was done for 12 weeks. Treatment group was given standard therapy and dl-α-tocopherol 10 -15 mg/kgBW/day plus ascorbic acid in the same dose, twice daily orally. Control group was given steroid therapy (standard) and placebo. Serum level of ox-LDL, sCD36, sVCAM-1 were measured by ELISA and NO by colorimetri. Analysis was done by Wilcoxon, independent t test or Mann-Whitney U test. Results: The mean level of pre and posttest of ox-LDL (127.2 to 89.5 U/L), sVCAM-1(929.4 to 868.4 ng/mL) and NO (8.9 to 8.5 μM/L) were decreased, but the level of sCD36 (72.5 to 123.5 ng/mL) increased in the treatment group. In control group, the mean level of ox-LDL(125.2 to 76.7 U/L), sVCAM-1(1231.2 to 1008.0 ng/mL), NO ( 8.2 to 7.9 μM) were decreased, but sCD36 (56.9-61.7 ng/mL) was increased. The Wilcoxon test of ox-LDL levels showed p :0.039 in treatment group and p=0.001 in control group. P value in treatment and control group of sCD36 levels were 0.163 and 0.088; sVCAM-1 levels p value = 0.306 & 0.122 and NO levels were p value =0.983 and 0.760. The Δ level of ox-LDL on treatment group compared to control was -37.7vs - 48.6U/L ; Δ sCD36: 51.1vs 17.2ng/mL; Δ sVCAM-1: -61.0 vs –223ng/mL ; Δ NO: -0.4 vs -0.6mg/dL. P value of Δ ox-LDL, ΔsVCAM-1, Δ sCD36 , ΔNO were 0.594, 0.327, 0.883, 0.864, respectively. According to remission state at the end of the study p value level of ox-LDL, Δ ox-LDL and level of sVCAM-1 in treatment group were 0,016; 0,047 and 0,000 respectively. Conclusions: Combined supplementation of dl-α-tocopherol and ascorbic acid 10 –15 mg/kgBW/day for 12 weeks decreased of stress oxidative and endothelial disfunction biomarker in remission state of the treatment group but did not effective to decrease level of Δ ox-LDL, Δ sCD36, Δ sVCAM –1 and Δ NO between two groups. Keywords: Nephrotic syndrome, antioxidant, oxidative stress, endothelial dysfunction