Pengaruh Pemberian Kombinasi Ekstrak Gambir (Uncaria gambier Roxb) dan Angiotensin Receptor Blocker (ARB) terhadap Kadar Transforming Growth Factor-Beta (TGF- β), Ekspresi Nadph Oxidase 4 (NOX4) aan Derajat Glomerulosklerosis pada Tikus Galur Wistar Model Sindrom Nefrotik

Abstract

Background: Nephrotic syndrome (NS) is the most common glomerular disease found in children. Proteinuria induces profibrotic and proinflammatory cytokines that play a role in extracellular matrix synthesis, differentiation, and proliferation of mesangial cells which cause glomerulosclerosis. SRA inhibitors, especially ARB, act as anti-proteinuria and formation of fibrotic tissue. The KDIGO recommends ARBs to treat proteinuria in steroid-resistant nephrotic syndrome. Gambier extract contains the active ingredient catechin which has been proven to have an antioxidant effect by increasing SOD and reducing proteinuria in animal models of NS. Objective: To prove that the combination of gambier extract and ARB can improve kidney damage by reducing TGF- levels, NOX4 expression and the degree of glomerulosclerosis in NS model rats. Methods: This research was a pure experimental study using experimental animals with a posttest with a control group design. The research was carried out from September 2022 to January 2023 at the Pharmacology and Therapeutics Laboratory, Integrated Laboratory, and Department of Anatomical Pathology, Faculty of Medicine, University of North Sumatra. The research subjects used male white rats of the Wistar strain (Rattus norvergicus, sp) aged 8 weeks and weighing 200 – 350 g. The research subjects were randomly selected and the sample groups were divided into 5 groups, namely group K1 (normal control group rats), group K2 (rats induced by injection of PAN + aquabides), group K3 (rats induced by injection of PAN + gambier extract at a dose of 26 mg/ 200 g BW), group K4 (rats induced by injection of PAN + ARB (losartan) dose of 10 mg/kg body weight) and group K5 (rats induced by injection of PAN + gambier extract combination dose of 26 mg/200 g BW and ARB (losartan) 10 mg/kg BW). The parameters tested in this study were TGF- levels, NOX4 expression using the quick score (QS) system assessment, and the degree of glomerulosclerosis using the glomerular sclerosis index (GSI) in kidney tissue on the 14th day after treatment. Results: The research subjects consisted of 30 rats divided into 5 groups. Examination of urine protein levels after 14 days of treatment showed an increase in the average urine protein levels in all groups of rats. The mean increase in urine protein levels was greatest in the K2 group (46.73 mg/ml ± 30.52), and the mean increase in proteinuria levels was least in the K4 group (0.17 mg/ml ± 0.13). The mean TGF-β level was highest in K2 (0.99 ± 0.33), and the lowest mean TGF-β level was in K5 (0.33 ± 0.22). The results of the NOX4 expression assessment were based on the QS value. The highest score was in the K2 group (QS 9), and the lowest NOX4 expression was in the combination of gambier extract and ARB in K5 with a mean QS of 3.2 (SD = 2.17). The degree of glomerulosclerosis based on the GSI value was highest in K2 group rats (3.8 ± 0.08), and the lowest degree of glomerulosclerosis was in the K3 group (0.11 ± 1.38). Conclusion: Administering a combination of gambier extract and ARB (losartan) reduced TGF-β levels better than gambier extract or ARB (losartan), reduced NOX4 expression greater than gambier extract or ARB (losartan), and the combination of gambier extract and ARB (losartan) reduced the degree of glomerulosclerosis is no different from administering gambier extract or ARB (losartan).