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Telmisartan inhibits the progression of cardiomyopathy in daunorubicin treated rats: the role of advanced glycation end products Arozal, Wawaimuli; Watanabe, Kenichi; Veeraveedu, Punniyakoti T.; Ma, Meilei; Nafrialdi, Nafrialdi
Medical Journal of Indonesia Vol 20, No 4 (2011): November
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1266.695 KB) | DOI: 10.13181/mji.v20i4.461

Abstract

Background: Anthracyclines have been reported to induce  cardiotoxicity through mechanisms involving formation of  advanced glycation end-products (AGEs), including pentosidine and Nє-(carboxymethyl) lysine (CML). We investigated the  potential utility of telmisartan (TML), an angiotensin II receptor antagonists (ARB) on anthracycline-induced cardiotoxicity.Methods: Three groups of Sprague-Dawley rats were treated as follows: The first group received daunorubicin (DNR) 3 mg/kgBW every alternating day to reach a cumulative dose of 9 mg/kg DNR . The second group received DNR plus TLM at a dose10 mg/kgBW, by oral gavage for 6 weeks, and the third group served as control group (CTL) which only received vehicle of DNR. Mean blood pressure (MBP) peak left ventricular pressure (LVP), LV end-diastolic pressure (LVEDP), and intra-ventricular  contractility (±dP/dt) were recorded by using Powerlab instrumentation. Ejection fraction (EF), and fractional shortening (FS) were measured by echocardiography. Expression of receptor of AGE (RAGE), pentosidine and CML were measured by  immunohistochemistry and Western blot in LV tissue.Results: DNR treatment was associated with significant  weakening of some hemodynamic parameters which couldbe reversed by TML (LVP: 124.3 ± 6.0; 111 ± 7; and 115.1 ± 5.4 mmHg, respectively in CTL, DNR and DNR-TLM groups; LVEDP: 7.5 ± 0.9; 10.7 ± 0.3; 8.7 ± 0.4 mmHg, respectively; +dP/dt: 6813 ± 541; 4800 ± 345; 5950 ± 398 mmHg/s, respectively). The same phenomenons were also observed on echocardiographic parameters (EF: 78.9 ± 1.8; 59.6 ± 1.4; 76.2 ± 2.75 %, resepectively; FS: 42.8 ± 1.7; 29.1 ± 1.3; 41 ± 2.7 %) respectively. Expression of RAGE as well as pentosidine and CML were increased in DNR-rats. TML treatment ameliorated these changes.Conclusion: These results suggested the role of AGE formation in DNR-induced cardiotoxicity and telmisartan could inhibit the progression of cardiac toxicity at least in part by reduction RAGE expressiom. (Med J Indones 2011; 20:255-62)Keywords: advanced glycation end product, anthracyline, cardiotoxicity, daunorubicin, telmisartan
The Effect of Mangiferin Against Brain Damage Caused by Oxidative Stress and Inflammation Induced by Doxorubicin Siswanto, Soni; Arozal, Wawaimuli; Juniantito, Vetnizah; Grace, Agatha; Agustini, Femmi Dwinda; Nafrialdi, .
HAYATI Journal of Biosciences Vol. 23 No. 2 (2016): April 2016
Publisher : Bogor Agricultural University, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (642.703 KB) | DOI: 10.4308/hjb.23.2.51

Abstract

Doxorubicin (DOX) is an anthracycline antibiotic used for anticancer therapy. However, this agent can cause various systemic side effects including cognitive impairments in chronic use. Brain damage due to DOX is caused by an increase of tumor necrosis factor-alpha (TNF-α) level in the brain. Increased TNF-α can further lead to chronic inflammation which can lead to neuronal deaths or neurodegenerative diseases. Mangiferin (MAG), a compound extracted from Mangifera indica, has been found neuroprotective activities, but its effect on DOX-induced brain damage is unknown. This study aims to determine the effect of MAG on brain damage induced by DOX. Male Sprague-Dawley rats were induced by DOX intraperitoneally. MAG was given orally at the doses of 30 and 60 mg/kg bw for 7 consecutive weeks. The parameters measured were inflammatory and oxidative stress markers in brain tissue. Coadministration of MAG with DOX reduced inflammation which was marked by the reduction of TNF-α mRNA expression, decreased TNF-α level and reduction of oxidative stress marked by increase of superoxide dismutase level and decrease of malondialdehyde level. In conclusion, MAG was shown to have a neuroprotective effect on brain damage induced by DOX, partly due to inhibition of inflammation and oxidative stress.
Evaluation of Kidney Injury Molecule-1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) Urinary Levels for Detecting Kidney Dysfunction in Patients With Nasopharyngeal Cancer Treated With Cisplatin-Based Treatment Rejeki, Marliana Sri; Arozal, Wawaimuli; Setiabudy, Rianto; Atmakusuma, Djumhana
Indonesian Journal of Cancer Vol 12, No 2 (2018): April-June
Publisher : National Cancer Center - Dharmais Cancer Hospital

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (951.677 KB) | DOI: 10.33371/ijoc.v12i2.581

Abstract

Background: Cisplatin has a potency of causing nephrotoxicity. Serum BUN and creatinine levels have been well-known for detecting kidney dysfunction; while KIM-1 and NGAL urine levels are relatively new measurements. The study was aimed to evaluate urinary KIM-1 and NGAL level to detect kidney dysfunction in patients with advanced stage NPC who received cisplatin-based chemotherapy.Methods: The study was a cohort-prospective study with 3 subject groups, i.e. patients who had never received and who had received 75-100 mg/m2 cisplatin-based chemotherapy as well as those who had never received 40 mg/m2 cisplatin-based chemotherapy. The levels of urinary KIM-1, NGAL and serum level of BUN and creatinine were measured before and after receiving cisplatin. Statistical analyses were ANOVA, Pearson, Spearman, Kolmogorov-Smirnov test and SPSS version 22.0.Result: There was a significant difference of delta BUN level (p=0.0001) and delta urinary NGAL level (p = 0.025) before and after treatment in all three groups; while delta KIM-1 level showed no significant difference in all three groups (p=0.275). Cisplatin may cause accumulated nephrotoxicity, which has dose-dependent manner.Conclusion: Measuring urinary NGAL level can detect an early stage of kidney dysfunction; however, it still cannot replace the role of BUN. Measurement of urinary KIM-1 level cannot detect kidney dysfunction.
Efek Kombinasi Ekstrak Etanol Acalypha indica dan Centella asiatica pada Jantung Tikus Pascahipoksia: Gen Hif-1a, Troponin I dan Stres Oksidatif Edhiatmi, Marsetyo; Arozal, Wawaimuli; Purwaningsih, Erni H
Jurnal Jamu Indonesia Vol 1 No 2 (2016): Jurnal Jamu Indonesia
Publisher : Pusat Studi Biofarmaka Tropika LPPM IPB; Tropical Biopharmaca Research Center - Bogor Agricultural University

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1083.737 KB) | DOI: 10.29244/jji.v1i2.15

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Hipoksia meningkatkan pembentukan dan pelepasan spesies oksigen reaktif (ROS). Sel mempunyai mekanisme melindungi diri terhadap kerusakan akibat pembentukan ROS yang terjadi secara alami. Jika pembentukan radikal bebas terjadi berlebihan maka dapat menyebabkan stres oksidatif yang memicu kerusakan sel terutama pada jantung. Sehingga tubuh memerlukan asupan antioksidan. Acalypha indica dan Centella asiatica terbukti memiliki efek antioksidan dan melindungi banyak organ dari kondisi hipoksia, sehingga penelitian ini dilakukan dengan tujuan untuk mengetahui efek antioksidan kombinasi ekstrak etanol Acalypha indica dan Centella asiatica pada organ jantung tikus Spraque-Dawley pascahipoksia. Tiga puluh lima ekor tikus Sprague-Dawley jantan diinduksi hipoksia selama 7 hari dalam ruang khusus, kemudian diberi perlakuan. Ekstrak Acalypha indica, ekstrak Centella asiatica dan kombinasinya diberikan kepada kelompok tikus yang telah dibagi menjadi grup A (hipoksia dan diberi air), B (hipoksia dan diberi kombinasi Acalypha indica 200 mg/kgBB dan Centella asiatica 150 mg/kgBB), C (hipoksia dan diberi kombinasi Acalypha indica 250 mg/kgBB dan Centella asiatica 100 mg/kgBB), D (hipoksia dan diberi Acalypha indica 250 mg/kgBB), E (hipoksia dan diberi Centella asiatica 150 mg/kgBB), F (hipoksia dan diberi vitamin C 100mg/kgBB) dan kelompok normal. Perlakuan diberikan secara oral selama 7 hari setelah hipoksia. Parameter yang diamati adalah ekspresi mRNA HIF-1α, kadar MDA, aktivitas enzim SOD dan ekspresi mRNA cTnI. Tidak terdapat perbedaan bermakna pada ekspresi HIF-1α antara grup A dan kelompok tikus normal (p>0,05). Kadar MDA meningkat signifikan pada grup A (p<0,05) dibanding tikus normal. Kadar MDA grup D mengalami penurunan secara signifikan (p<0,05) dibanding grup A. Aktivitas SOD menurun signifikan pada grup A (p<0,05) dibanding tikus normal. Aktivitas SOD grup B dan E (p<0,05) mengalami peningkatan secara signifikan dibanding grup A. Grup B meningkat signifikan (p<0,05) dibanding grup E. Tidak terdapat perbedaan bermakna antar kelompok perlakuan pada Ekspresi cTnI. Tidak terdapat korelasi antara kadar MDA dan aktivitas SOD serta ekspresi mRNA HIF-1a dan mRNA cTnI. Pemberian kombinasi ekstrak Acalypha indica dan Centella asiatica tidak dapat membantu memproteksi kerusakan jantung pascahipoksia.
Cardioprotective Effect of Quercetin in 5/6-Nephrectomized Rats: Focus on Myocardial fibrosis and Oxidative Stress Yuliani, Tri; Louisa, Melva; Arozal, Wawaimuli; Soetikno, Vivian; Nafrialdi, Nafrialdi; Dewijanti, Indah D
Jurnal Jamu Indonesia Vol 2 No 3 (2017): Jurnal Jamu Indonesia
Publisher : Pusat Studi Biofarmaka Tropika LPPM IPB; Tropical Biopharmaca Research Center - Bogor Agricultural University

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (994.684 KB) | DOI: 10.29244/jji.v2i3.37

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Uremic cardiomyopathy is the leading cause of death in patients with chronic kidney disease. Fluid overload and oxidative stress play important roles in its pathogenesis. This study aims to determine the effect of quercetin on uremic cardiomyopathy in 5/6-nephrectomized rats. To our knowledge, its cardioprotective effect on uremic cardiomyopathy induced in rats by 5/6 nephrectomy has not been investigated yet. Uremia was induced surgically in male Sprague-Dawley rats via 5/6 nephrectomy. Quercetin was administered per orally at a dose of 100 mg/kg/day for 8 weeks prior to sacrifice. Meanwhile, captopril was administered at a dose of 10 mg/kg/day. Lipid peroxidation was assessed using TBARS reaction, while GPX activity was determined to explore the endogen antioxidant mechanism. Myocardial fibrosis was analyzed using Massons’ Trichrome staining and the level of NT-proBNP in plasma was measured as a marker of cardiac dysfunction. Nephrectomy 5/6 had no effects on plasma NT– proBNP levels, cardiac and plasma MDA levels, but induced mild myocardial fibrosis and significant increase in cardiac GPX activity in comparison with normal rat (p<0.05). However, administration of quercetin or captopril did not ameleriote those mild myocardial fibrosis and increased GPX activity. Uremic cardiomyopathy induced by 5/6 nephrectomy demonstrated mild myocardial fibrosis but preservation of cardiac function demonstrated by NT-proBNP levels. Increased of GPX activity in the nephrectomized-rats compared to the control rats (p<0.05) suggests induction of antioxidant defense mechanisms that might not be exhausted yet. This condition highlighted a compensatory phase which was unchanged following chronic administration of either quercetin or captopril.
Hewan Model Kanker Ovarium untuk Studi Preklinik dan Pengembangan Obat Kanker Ovarium Dwi Sandhiutami, Ni Made; Wuyung, Puspita Eka; Arozal, Wawaimuli; Louisa, Melva; Rahmat, Deni
JURNAL ILMU KEFARMASIAN INDONESIA Vol 17 No 2 (2019): JIFI
Publisher : Fakultas Farmasi Universitas Pancasila

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (495.923 KB) | DOI: 10.35814/jifi.v17i2.734

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Pengobatan pada karsinoma ovarium masih jauh dari optimal, model hewan masih diperlukan untuk mempelajari kanker ovarium tipe epitelial manusia. Hewan model kanker ovarium sangat penting untuk memahami patogenesis penyakit dan untuk menguji strategi pengobatan baru. Model karsinogenesis ovarium pada tikus telah dimodifikasi dan diperbaiki untuk menghasilkan lesi preneoplastik dan neoplastik ovarium yang secara patogen menyerupai kanker ovarium manusia.  Meskipun tumor ovarium spontan pada tikus telah dilaporkan, namun beberapa kekurangan dari penelitian yang telah ada menghalangi penggunaannya sebagai hewan coba model kanker ovarium. Karena itu, banyak upaya telah dilakukan untuk mengembangkan model hewan yang relevan untuk kanker ovarium. Model-model hewan coba dikembangkan secara akurat agar dapat mewakili perubahan seluler dan molekuler yang terkait dengan inisiasi dan perkembangan kanker ovarium manusia. Model hewan coba yang akurat memiliki potensi signifikan dalam memfasilitasi pengembangan metode yang lebih baik untuk deteksi dini dan pengobatan kanker ovarium. Beberapa model hewan coba kanker ovarium telah dilaporkan, termasuk manipulasi berbagai faktor reproduksi atau paparan karsinogen. Kemajuan terbaru dalam pemodelan kanker ovarium adalah menggunakan tikus yang direkayasa genetika.
POTENTIAL DELETERIOUS EFFECTS OF L-CITRULLINE SUPPLEMENTATION IN ISOPROTERENOL-INDUCED MYOCARDIAL INFARCTION: FOCUS ON NITROSATIVE STRESS Wikanendra, Gregorius Bhaskara; Arozal, Wawaimuli; Kusmardi, Kusmardi; Juniantito, Vetnizah; Laurentius, Andrea
Indonesian Journal of Pharmacy Vol 30 No 4, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjpharm30iss4pp269

Abstract

L-Citrulline shows potential activity as a supplement to prevent myocardial infarction through vasodilative and possible antioxidative effects but may be deleterious by causing nitrosative stress. This study determined the potentially deleterious effects of L-citrulline supplementation in isoproterenol-induced myocardial infarction with a focus on nitrosative stress. L-Citrulline supplementation was given orally at dosages of 300 or 600mg/kg body weight daily for 6 days. Myocardial infarction was induced in Wistar rats via subcutaneous injection of isoproterenol (85 mg/kg body weight (BW)) on day 4 and 5. Blood pressure was measured at the end of the study (day 6) and rats were sacrificed to collect heart tissue samples for a histopathological evaluation. The histopathological evaluation was done using hematoxylin and eosin staining for the myocardial damage evaluation and immunohistochemical (IHC) staining of arginase-2, inducible nitric oxide synthase (iNOS), and 3-nitrotyrosine to evaluate nitrosative stress. L-Citrulline supplementation failed to show a significant protective effect on blood pressure and exacerbated the decrease of diastolic blood pressure. Both low and high dose L-citrulline supplementation had a significant protective effect on myocardial damage compared to the isoproterenol group (p<0.01). L-Citrulline also caused increased nitrosative stress as shown by increased expression of arginase-2 and 3-nitrotyrosine on IHC staining but tended to show an ameliorative effect on iNOS expression. A significant increase in arginase-2 expression was detected between the high dose group and the other groups (p<0.01 vs. normal and isoproterenol groups; p<0.05 vs. low dose group). L-Citrulline supplementation increased 3-nitrotyrosine expression in a dose-dependent manner, which was significantly different compared to the normal group (low dose: p<0.013; high dose: p<0.003). L-Citrulline increased the production of nitrosative stress but resulted in less myocardial damage through its other effects.