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"[ABSTRAKDoksorubisin merupakan salah satu antikanker golongan antrasiklin yang efektif,untuk keganasan di darah. Akan tetapi, seperti antikanker konvensional padaumumnya, penggunaan doksorubisin dapat menyebabkan berbagai efek samping padaorgan lain, misalnya pada testis sehingga penggunaannya di klinis menjadi terbatas.Hal ini disebabkan karena mekanisme antikanker doksorubisin dapat jugamenimbulkan toksisitas pada testis. Peningkatan stress oksidatif adalah salah satumekanisme dapat menyebabkan kerusakan pada organ tersebut. Mangiferin sebagaizat antioksidan alami, terkandung dalam Mangifera Indica L. diperkirakan dapatdigunakan untuk mengurangi toksisitas testis. Namun sampai saat ini, belum adapenelitian yang mengeksplor efek proteksi mangiferin terhadap kerusakan oksidatiftestis yang diinduksi doksorubisin.Penelitian ini menggunakan tikus jantan Sprague Dawley, yang dibagi menjadi empatkelompok. Masing-masing kelompok terdiri dari enam ekor tikus. Tikus padakelompok kontrol negatif diberikan doksorubisin secara intraperitoneal (dosis total 15mg/kgBB) dan kelompok normal diberikan NaCl 0,9%. Mangiferin (dosis 30 dan 60mg/kg BB) diberikan oral selama tujuh minggu. Setelah, tujuh minggu tikusdimatikan dan testis dikumpulkan untuk analisis parameter stress oksidatif biokimiakadar MDA (malonedyaldehide), aktivitas SOD (Superoxide Dysmutase), perubahanhistologi dan apoptosis kaspase-9 dan kaspase-12. Hasil penelitian menunjukkanbahwa pemberian doksorubisin selama dua minggu dapat meningkatkan kadar MDA,menyebabkan kerusakan sel spermatogenik, sel Sertoli dan penciutan diametertubulus seminiferus testis, peningkatan ekspresi kaspase-9 di sisi luminal yangdiberikan doksorubisin. Pemberian mangiferin dosis 30 dan 60 mg/kg BB selamatujuh minggu dapat mengurangi kerusakan sel spermatogenik dan sel Sertoli tubulusseminiferus testis, penurunan kadar MDA dan penurunan ekspresi kaspase-9 padakelompok perlakuan diberikan doksorubisin dan mangiferin. Perbaikan parameterparameterini mengindikasikan bahwa mangiferin mempunyai efek proteksi terhadapkerusakan sel spematogenik dan sel sertoli tubulus seminiferus testis tikus yangdiberikan doksorubisin.

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ABSTRACTDoxorubicin, one of the anthracycline anticancer class, is effective especially in bloodmalignancy. However, as in the general use of the conventional anticancer-drugs.Doxorubicin can cause various side effects in other organs, such as the testes so thatits use in clinical become limited. This is because of the anticancer mechanism cancause cytotoxicity on testes. The increased oxidative stress is the main mechanismthat can be the causal. Mangiferin as a natural antioxidant substance, contained inMangifera Indica L., is expected to reduce the toxicity. The Antioxidants areexpected to reduce the toxicity of the testes. But until now, no studies have exploredthe effects of mangiferin protection against oxidative damage induced testiculardoxorubicin.This study used male Sprague Dawley rats, which were divided into four groups.Each group consisted of six mice. Rats in the negative control group was givenintraperitoneal doxorubicin (total dose 15 mg/kg) and the normal group was givennormal saline 0.9%. Mangiferin (doses of 30 and 60 mg/kg) was administered orallyfor seven weeks to the treatment gtoups (both DOX and MAG were given). Afterseven weeks-off, testes of mice were collected for analysis of biochemical parametersi.e. oxidative stress levels of MDA and SOD activity, histology and apoptosis of thecaspase-9 and of the caspase-12. The results showed that administration ofdoxorubicin for two-weeks can cause damage to Sertoli, spermatogenic cells andshrinking of diameter of testicular seminiferous tubules, increasing the levels ofMDA, increasing in the expression of caspase-9 on the luminal side in the treatmentgroup was given doxorubicin. This possibility of the doxorubicin dose given is tootoxic to the testes in this study. Mangiferin dose administration of 30 and 60 mg / kgfor seven-weeks can reduce the damage of Sertoli and spermatogenic cells of thetesticular seminiferous tubules, decrease levels of MDA, reduce Sertoli,spermatogenic cell and diameter of the testicular seminiferous tubulus damage,decrease caspase-9 expression only on luminal side of the seminiferus tubulus in thegroups given both of doxorubicin and mangiferin. these parameters indicate thatmangiferin, which has antioxidant?s activity, provides protective effects againstoxidative damage in spematogenic and Sertoli cell testicular seminiferous tubules ofmice given doxorubicin, Doxorubicin, one of the anthracycline anticancer class, is effective especially in bloodmalignancy. However, as in the general use of the conventional anticancer-drugs.Doxorubicin can cause various side effects in other organs, such as the testes so thatits use in clinical become limited. This is because of the anticancer mechanism cancause cytotoxicity on testes. The increased oxidative stress is the main mechanismthat can be the causal. Mangiferin as a natural antioxidant substance, contained inMangifera Indica L., is expected to reduce the toxicity. The Antioxidants areexpected to reduce the toxicity of the testes. But until now, no studies have exploredthe effects of mangiferin protection against oxidative damage induced testiculardoxorubicin.This study used male Sprague Dawley rats, which were divided into four groups.Each group consisted of six mice. Rats in the negative control group was givenintraperitoneal doxorubicin (total dose 15 mg/kg) and the normal group was givennormal saline 0.9%. Mangiferin (doses of 30 and 60 mg/kg) was administered orallyfor seven weeks to the treatment gtoups (both DOX and MAG were given). Afterseven weeks-off, testes of mice were collected for analysis of biochemical parametersi.e. oxidative stress levels of MDA and SOD activity, histology and apoptosis of thecaspase-9 and of the caspase-12. The results showed that administration ofdoxorubicin for two-weeks can cause damage to Sertoli, spermatogenic cells andshrinking of diameter of testicular seminiferous tubules, increasing the levels ofMDA, increasing in the expression of caspase-9 on the luminal side in the treatmentgroup was given doxorubicin. This possibility of the doxorubicin dose given is tootoxic to the testes in this study. Mangiferin dose administration of 30 and 60 mg / kgfor seven-weeks can reduce the damage of Sertoli and spermatogenic cells of thetesticular seminiferous tubules, decrease levels of MDA, reduce Sertoli,spermatogenic cell and diameter of the testicular seminiferous tubulus damage,decrease caspase-9 expression only on luminal side of the seminiferus tubulus in thegroups given both of doxorubicin and mangiferin. these parameters indicate thatmangiferin, which has antioxidant’s activity, provides protective effects againstoxidative damage in spematogenic and Sertoli cell testicular seminiferous tubules ofmice given doxorubicin]"

"Hati merupakan organ yang berperan penting dalam metabolisme zat terutama obat-obatan sehingga organ ini rentan terhadap kerusakan. Salah satu obat yang dapat menyebabkan kerusakan hati adalah doksorubisin. Hal ini disebabkan karena struktur kimia dan proses metabolisme doksorubisin dapat membentuk sejumlah metabolit yang bersifat radikal bebas. Radikal bebas yang diproduksi doksorubisin menyebabkan berkurangnya antioksidan endogen, mengganggu keseimbangan besi intraselular sehingga mencetuskan kerusakan oksidatif. Berdasarkan hal tersebut, kerusakan oksidatif yang dipicu oleh doksorubisin dapat dicegah dengan pemberian antioksidan eksogen. Salah satu bahan bioaktif yang terbukti memiliki efek antioksidan adalah mangiferin. Efek antioksidannya berhubungan dengan sifat scavenging radikal bebas dan sifat kelator besinya. Pemberian senyawa ini diasumsikan dapat melindungi atau mencegah kerusakan oksidatif sel. Penelitian ini bertujuan untuk membuktikan efek protektif mangiferin terhadap kerusakan hati pada tikus yang diberikan doksorubisin. Pada penelitian ini, tikus dibagi menjadi lima kelompok, masing-masing kelompok terdiri dari lima ekor tikus. Tikus pada kelompok perlakuan diberikan injeksi doksorubisin intraperitoneal (dosis kumulatif 15 mg/kgBB) dan kelompok kontrol diberikan minyak jagung oral. Mangiferin (dosis 50 mg/kgBB dan 100 mg/kgBB) dan silymarin diberikan secara oral selama lima minggu. Setelah lima minggu, tikus dimatikan, darah dan jaringan hati dikumpulkan untuk analisis histopatologi dan penentuan SGOT, SGPT, MDA, SOD dan GSH. Hasil penelitian menunjukkan bahwa pemberian doksorubisin dengan dosis kumulatif 15 mg/kgBB selama dua minggu dapat menyebabkan kerusakan sel hati, meningkatkan kadar MDA, dan menurunkan pertahanan antioksidan endogen di hati. Pemberian mangiferin 50 dan 100 mg/kgBB selama lima minggu dapat mengurangi kerusakan sel hati yang ditandai dengan penurunan aktivitas SGPT dan SGOT, penurunan kadar MDA, dan peningkatan aktivitas SOD dan kadar GSH sel hati (p < 0.05). Perbaikan pada parameter-parameter ini mengindikasikan bahwa mangiferin memiliki efek proteksi terhadap kerusakan hati pada tikus yang diberikan doksorubisin.

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Liver is an organ that plays an important role in the metabolism of xenobiotics. However, since it is actively involved in drug metabolism, it is also subject to damage caused by toxic drugs or metabolites. One of the drugs that caused liver damage is doxorubicin. The liver damaging effect of doxorubicin is determined to its chemical structure and toxic metabolites which can produce free radical molecules. The free radicals produced by doxorubicin cause depletion of antioxidant in the body, disrupt the balance of intracellular iron and lead to oxidative stress. Based on this consideration, the oxidative stress induced by doxorubicin should be diminished by means of exogenous antioxidant administration. One of the bioactive ingredient that has been shown to have antioxidant effects is mangiferin; its antioxidant properties relate to free radical scavenging and iron chelating effect. This compound is expected to protect against or prevent oxidative damage caused by doxorubicin to cells.

This study aims to investigate the protective effect of mangiferin against liver damage-induced doxorubicin. There were five groups of rats, consisting five each group. The animals in the study groups were treated with intraperitoneal doxorubicin (cumulative dose 15 mg/kgBW for two weeks) and control group was given oral corn oil. Mangiferin (dose 50 mg/kgBW and 100 mg/kgBW) and silymarin were given daily by oral administration for five weeks. After sacrifice, blood and liver tissue samples were collected for histopathological analysis and determination of SGOT, SGPT, MDA, SOD, and GSH.

The results showed that administration of cumulative doses of doxorubicin to 15 mg/kgBW for two weeks caused liver cell damage, increased MDA level and decreased activities of SOD and GSH level in liver. The supplementation of mangiferin 50 and 100 mg/kgBW for five weeks reduced liver cell damage as shown by decreased activities of SGPT and SGOT, decreased MDA level, and increased activities of liver SOD and GSH levels. (p <0.05). These results showed that mangiferin has a protective effect against liver damage induced by doxorubicin in the rat."

"Latar belakang. Doksorubisin dikenal sebagai antikanker yang sangat poten, namun penggunaanya dibatasi oleh toksisitas terhadap berbagai organ vital, salah satunya jantung. Mekanisme molekuler kardiotoksisitas doksorubisin berhubungan dengan produksi radikal bebas berlebih yang menyebabkan penurunan ekspresi gen-gen yang mengkode protein regulator kalsium intrasel sehingga terjadi gangguan homeostasis kalsium intrasel yang menyebabkan aktivasi jalur apoptosis intrinsik yang dimediasi caspase, terutama caspase-9 dan caspase-12. Stres oksidatif akibat DOX juga menyebabkan peningkatan produksi sitokin proinflamasi yang berperan dalam terjadinya apoptosis. Mangiferin merupakan salah satu kandidat potensial senyawa kardioprotektor untuk terapi doksorubisin, akan tetapi mekanisme molekulernya belum diketahui dengan pasti. Penelitian ini bertujuan untuk mengetahui apakah mekanisme molekuler mangiferin berhubungan dengan regulasi kalsium intraseluler. Metode. Penelitian dilakukan terhadap tikus Sprague Dawley jantan yang diinduksi doksorubisin dengan dosis total 15 mg/kg BB. Pemberian mangiferin dilakukan dengan dosis 30 dan 60 mg/kg BB secara oral selama tujuh minggu. Parameter yang diamati adalah ekspresi protein regulator Ca2+ intrasel yaitu SERCA2a, parameter apoptosis (caspase-12 dan caspase-9), kadar kalsium sitosol dan mitokondria, serta parameter inflamasi (TNF-α). Hasil. Induksi doksorubisin menyebabkan penurunan ekspresi SERCA2a, disertai peningkatan ekspresi gen pro-apoptosis yakni caspase-12 dan caspase-9 serta peningkatan derjat inflamasi dan kerusakan jantung. Pemberian mangiferin menyebabkan peningkatan ekspresi SERCA2a, penurunan ekspresi caspase-12 dan caspase-9 serta penurunan derajat inflamasi. Kesimpulan. Berdasarkan hasil tersebut, dapat disimpulkan bahwa normalisasi homeostasis kadar kalsium intrasel merupakan bagian dari mekanisme kardioproteksi mangiferin.

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Background. Doxorubicin is well known as a potent anticancer agent despite its toxicity on various vital organs, especially the heart. The molecular mechanism of doxorubicin cardiotoxicity revolves around the overproduction of free radicals which cause downregulation of genes encoding calcium regulatory proteins, leading to disturbance of calcium homeostasis and activation of intrinsic apoptotic pathway mediated by caspases, particularly caspase-12 and caspase-9. Doxorubicin cardiotoxicity is also accompanied by inflammation that is crucial for apoptosis. Mangiferin is currently studied as cardioprotective agents for doxorubicin therapy. However, its molecular mechanism has yet been revealed. This study was aimed to determine whether cardioprotective effect of mangiferin is caused by its effect on intracellular calcium regulation.

Method. Male Sprague Dawley rats were induced by doxorubicin with a total dose of 15 mg/kg BW. Mangiferin was given orally at the dose of 30 and 60mg/kg BW for seven weeks. The parameters examined were mRNA expressions levels of calcium regulatory gene (SERCA2a), proapoptotic genes (caspase-9 and caspase-12) and proinflammatory cytokine gene (TNF-α), as well as mitochondrial and cytosolic calcium levels.

Result. It was found that doxorubicin caused downregulation of SERCA2a expression and increased the expression of both proapoptotic genes. Interestingly, we found that mangiferin could attenuate those things above by increasing SERCA2a expression as well as decreasing caspase-9 and caspase-12 expressions, while ameliorating inflammation.

Conclusion. Based on this finding, we suggest that the cardioprotective effect of mangiferin is at least in part due to the regulation of intracellular calcium homeostasis."

"Latar belakang. Doksorubisin (DOK), suatu antibiotika antrasiklin, digunakan secara luas untuk terapi antikanker, namun penggunaan DOK dapat menimbulkan efek samping, salah satunya gangguan kognitif. Penggunaan kemoterapi berbasis DOK menunjukkan hingga 76% pasien mengalami penurunan kognitif. Kerusakan otak akibat penggunaan DOK disebabkan oleh peningkatan TNF-α di otak melalui uptake reseptor di sawar darah otak dan peningkatan produksi melalui aktivasi NF-κB. Peningkatan TNF-α lebih lanjut dapat menyebabkan inflamasi kronis yang dapat menimbulkan kematian sel saraf atau penyakit degenerasi saraf. Mangiferin (MAG) merupakan salah satu senyawa neuroprotektif, akan tetapi efek terhadap kerusakan otak akibat pemberian DOK belum diketahui. Penelitian ini bertujuan untuk mengetahui efek MAG terhadap kerusakan otak yang ditimbulkan oleh pemberian DOK. Metode. Penelitian dilakukan terhadap tikus Sprague-Dawley yang diinduksi menggunakan DOK dengan dosis total 15 mg/kgBB secara i.p mulai minggu kedua. Pemberian MAG dilakukan secara p.o dengan dosis 30 dan 60 mg/kgBB selama 7 minggu. Parameter yang diamati adalah fungsi kognitif, inflamasi (TNF-α, NF-κB dan iNOS), stres oksidatif (SOD dan MDA) dan histopatologi dengan pewarnaan HE. Hasil. Pemberian DOK menyebabkan gangguan kognitif yang ditandai dengan penurunan penggiliran labirin Y dan penurunan indeks diskriminasi pada pengenalan obyek baru, disertai peningkatan parameter inflamasi yaitu ekspresi TNF-α, NF-κB dan iNOS. Pemberian MAG bersama DOK menyebabkan peningkatan fungsi kognitif, penurunan inflamasi dan penurunan stres oksidatif serta histopatologi dewan pewarna HE. Kesimpulan. Berdasarkan hasil pemeriksaan parameter pada penelitian mengindikasikan bahwa mangiferin memiliki efek neuroproteksi terhadap pemberian DOK.

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Introduction. Doxorubicin (DOK), an anthracycline antibiotic, is widely used for anticancer therapy, but the use of DOK causing side effects, one of them is cognitive impairment. Up to 76% of patients experienced cognitive decline caused by DOK-based chemotherapy. Brain damage due to the use of DOK lead by an increase in TNF-α in the brain through the receptors uptake in the blood brain barrier and increasing production through activation of NF-κB. Increased TNF-α can further lead to chronic inflammation which can lead nerve cells death or nerve degeneration diseases. Mangiferin (MAG) is one of the neuroprotective compound, but the effect on brain damage induced by DOK is still unknown. This study aims to determine the effect of MAG on brain damage induced by DOK.

Methods. Research carried out on Sprague-Dawley rats induced by DOK i.p with total dose 15 mg/kg that divided into 6 dose and given within 2 weeks, started from 2nd week. The rats was administrated by MAG p.o with dose 30 and 60 mg/kg daily for 7 weeks. Parameters measured were cognitive function, inflammatory parameters (TNF-α, NF-κB and iNOS), oxidative stress parameters (SOD and MDA) and histopatology using HE staining.

Results. DOK cause cognitive disorders that characterized by decreased Y maze alteration and discrimination index in new object recognition, and accompanied by increasing inflammatory parameters that showed in increasing TNF-α, NF-κB and iNOS expressions. Coadministration MAG with DOK led an increasing on cognitive function, reducing the inflammation and oxidative stress.

Conclusion. Based on the results of the study, MAG indicated has a neuroprotective effect on brain damage induced by DOK"

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Latar belakang: Kondisi besi berlebih dalam tubuh dapat terjadi karena besi yang masuk mengalami peningkatan atau salah satu komponen ekskresi besi mengalami gangguan. Kondisi ini dapat terjadi pada pasien talasemia, terutama yang mendapat transfusi darah secara rutin. Transfusi darah rutin dapat menyebabkan kondisi kelebihan besi dan akumulasi besi pada berbagai organ, termasuk limpa. Oleh karena itu, pasien membutuhkan obat kelasi besi, tetapi harganya mahal dan banyak efek samping. Penelitian sebelumnya menyimpulkan bahwa mangiferin memiliki efek mengikat besi, namun bioavailabilitasnya rendah. Oleh karena itu, penelitian ini bertujuan untuk membandingkan efek mangiferin dan mangiferin dalam nanopartikel kitosan-alginat sebagai obat kelasi besi.

Metode: Limpa tersimpan dari dua puluh lima tikus jantan Sprague-Dawley dibagi ke dalam 5 kelompok, yaitu tikus normal (N), tikus yang diberi besi berlebih (KN), tikus yang diberi mangiferin 50 mg/kgBB (M50), tikus yang diberi mangiferin dalam nanopartikel kitosan-alginat 50 mg/kgBB (MN50), dan tikus yang diberi mangiferin dalam nanopartikel kitosan-alginat 25 mg/kgBB (MN25). Perlakuan pada hewan coba dilakukan selama 28 hari. Setelah 28 hari, tikus dikorbankan dan organ limpa diambil untuk pengukuran kadar besi pada limpa. Pengukuran menggunakan spektrofotometer serapan atom dengan panjang gelombang 248,3 nm.

Hasil: Dari pengukuran, rata-rata kadar besi organ limpa (µg Fe/g jaringan) pada kelompok M50 (1200,80±126,05), kelompok MN50 (918,38±427,63), dan kelompok MN25 (645,73±178,89). Ketiga kelompok tersebut tidak berbeda signifikan dengan kelompok KN. Namun, terdapat perbedaan signifikan antara kelompok M50 dan MN25 (p=0,006).

Kesimpulan: Mangiferin dalam nanopartikel kitosan-alginat dosis 25 mg/kg BB dapat menurunkan kadar besi di limpatikus yang diberi besi berlebih lebih baik dari mangiferin saja.

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Background: Iron overload is a condition caused by increased intake or disruption of the excretion process. Thalassemia is one of the causes of iron overload, especially transfusion-dependent thalassemia (TDT). Transfusion-dependent thalassemia can cause iron overload and iron accumulation in several organs, including the spleen. Therefore, the patients also need iron chelator to excrete excessive iron, but it is expensive and has many side effects. The previous study shows mangiferin could act as an iron chelator but has low bioavailability. Therefore, we conducted this experimental study to compare mangiferin and mangiferin in chitosan-nanoparticle as an iron chelating agent.

Methods: Spleens from twenty five male Sprague-Dawley rats were divided into 5 groups, which are normal (N), negative control (KN), mangiferin 50 mg/kgBW (M50), mangiferin in chitosan-alginate nanoparticle 50 mg/kgBW (MN50), and mangiferin in chitosan-alginate nanoparticle 25 mg/kgBW (MN25). After 28 days, rats were sacrificed and the spleen were taken to measure the iron level using atomic absorbance spectrophotometer at 248,3 nm wavelength. 

Results: From the measurement, the mean of iron level in spleen (µg Fe/g tissue) of M50 group (1200,80±126,05), MN50 group (918,38±427,63), and MN25 group (645,73±178,89). In this study, those three groups did not significantly different with negative control group (KN). But, there was a significant difference between M50 and MN25 groups (p=0,006).

Conclusion: Mangiferin in chitosan-alginate nanoparticles 25 mg/kg BW decreases the iron level in spleen of the iron overload rats better than mangiferin only.

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Latar belakang: Besi berlebih yang terakumulasi di dalam tubuh akibat transfusi darah berulang pada pasien talasemia-β mayor dapat menyebabkan kerusakan pada banyak organ, terutama hati. Besi berlebih di dalam tubuh dapat dikurangi kadarnya dengan agen kelasi besi. Mangiferin yang berasal dari sumber alami telah terbukti memiliki kemampuan sebagai agen kelasi besi, antioksidan, dan antiinflamasi. Namun, mangiferin memiliki bioavailabilitas yang rendah. Salah satu cara untuk meningkatkan bioavailabilitas mangiferin yaitu menjadikannya dalam formulasi kitosan-alginat nanopartikel. Penelitian ini bertujuan untuk membuktikan efek mangiferin dan mangiferin dalam kitosan-alginat nanopartikel pada gambaran histopatologi organ hati tikus yang diberi besi berlebih.

Metode: Dua puluh lima tikus Sprague-Dawley dibagi menjadi 5 kelompok: normal (N), kontrol negatif (KN), terapi mangiferin dosis 50 mg/kg BB/hari (M50), terapi mangiferin dalam kitosan-alginat nanopartikel dosis 50 mg/kg BB/hari (MN50), dan terapi mangiferin dalam kitosan-alginat nanopartikel dosis 25 mg/kg BB/hari (MN25). Setelah diberikan perlakuan selama 28 hari, tikus dikorbankan dan organ hati diambil untuk membuat preparat jaringan. Pengamatan dilakukan di bawah mikroskop dengan menggunakan uji lapang pandang. Parameter yang diteliti adalah gambaran nekrosis, inflamasi, dan steatosis hati.

Hasil: Pemberian mangiferin dapat memperbaiki kerusakan hati akibat besi berlebih dalam bentuk nekrosis, inflamasi, dan steatosis, secara signifikan (p <0,05) dibandingkan dengan kelompok KN. MN50 dan MN25 menunjukkan perbaikan yang signifikan pada nekrosis dan steatosis hati dibandingkan dengan M50. Kemampuan mangiferin dalam kitosan-alginat nanopartikel untuk memperbaiki nekrosis, inflamasi, dan steatosis hati, menunjukkan kecenderungan meningkat secara berurutan dari M50, MN50, dan MN25.

Kesimpulan: Mangiferin dalam kitosan-alginat nanopartikel lebih baik dalam memperbaiki gambaran histopatologi hati tikus yang diberi besi berlebih dibandingkan dengan mangiferin saja.

 

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Background: Iron overload that accumulates in the body due to repeated blood transfusions in β-thalassemia major can cause damage to many organs, especially the liver. Iron overload can be reduced by iron-chelating agents. Mangiferin from natural sources has been proven to have the ability as an iron-chelating agent, antioxidant and anti-inflammatory agent. However, mangiferin has a low bioavailability. To increase mangiferin bioavailability, formulated mangiferin in chitosan-alginate nanoparticles has been made. This study is aimed to determine the effect of mangiferin and mangiferin in chitosan-alginate nanoparticles on liver histopathology of iron overload rats.

Methods: Twenty-five Sprague-Dawley rats were divided into 5 groups: normal (N), negative control (KN), mangiferin therapy dose of 50 mg/kg BW per day (M50), mangiferin in chitosan-alginate nanoparticles therapy dose of 50 mg/kg BW per day (MN50), and mangiferin in chitosan-alginate nanoparticles therapy dose of 25 mg/kg BW per day (MN25). After treatment, the rats were sacrificed and the livers were taken to make preparations. Observations under the microscope were carried out using visual field test. The parameters studied were features of liver necrosis, inflammation, and steatosis.

Results: Mangiferin treatment can ameliorates the liver damage due to iron overload in the form of necrosis, inflammation, and steatosis, significantly (p < 0.05) compared to the KN group. MN50 and MN25 show significant amelioration in liver necrosis and steatosis compared to the M50. The ability of mangiferin in chitosan-alginate nanoparticles to ameliorates liver necrosis, inflammation, and steatosis, show a tendency to increase sequentially from M50, MN50, and MN25.

Conclusion: Mangiferin in chitosan-alginate nanoparticles ameliorates the liver histopathological features of iron overload rats better than mangiferin alone.

 

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"Latar belakang: Kelebihan besi akibat transfusi darah terus-menerus dapat dialami penderita penyakit hemoglobinopati seperti talasemia. Di Indonesia, prevalensi penderita talasemia terbilang cukup tinggi. Untuk mengatasi kondisi tersebut, dibutuhkan terapi kelasi besi namun, terapi kelasi yang tersedia memiliki banyak kelemahan. Oleh karena itu, dilakukan studi terhadap mangiferin yang memiliki efek kelasi besi. Oleh karena bioavailabilitas mangiferin rendah, perlu dibentuk sebagai nanopartikel kitosan-alginat. Pada studi terdahulu, efek mangiferin dalam nanopartikel kitosan-alginat terhadap kadar MDA pada jantung tikus dengan kelebihan besi belum pernah dibuktikan Tujuan: Penelitian ini bertujuan untuk menilai kemampuan mangiferin dan mangiferin dalam nanopartikel kitosan-alginat terhadap kadar MDA organ jantung tikus dengan kondisi kelebihan besi Metode: Sebanyak 25 ekor tikus Sprague-Dawley dibagi dalam 5 kelompok: kontrol (N), tikus kelebihan besi (IO), dan kelompok terapi per oral yaitu tikus IO yang diberi mangiferin dosis 50 mg/kgBB (IO + M50), mangiferin nanopartikel kitosan-alginat dosis 50 mg/kgBB (IO + MN50), dan mangiferin nanopartikel kitosan-alginat dosis 25 mg/kgBB (IO + MN25). Tikus kelebihan besi diinjeksikan iron dextran intraperitoneal 15 mg, dua kali seminggu selama empat minggu. Kadar MDA organ jantung diukur menggunakan spektrofotometer. Hasil: Rerata kadar MDA jantung tikus pada kelompok N, IO, MN, MN50, dan MN25 secara berurutan adalah 7,36, 2,53, 5,64, 4,80, dan 9,36 nMol/mg. Tidak ditemukan penurunan kadar MDA pada kelompok terapi terhadap kelompok IO. Meskipun begitu, terdapat perbedaan signifikan kadar MDA jaringan jantung tikus Sprague-Dawley pada setiap kelompok (ANOVA, p = 0,048). Ditemukan juga perbedaan bermakna antara kelompok IO dengan MN (P= 0,03) dan MN 50 (P=0,041). Kesimpulan: Mangiferin dan mangiferin dalam nanopartikel kitosan-alginat tidak mampu menurunkan kadar MDA pada jantung tikus dengan keadaan besi berlebih.

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Introduction: Iron overload due to continuously blood transfusions is a problem that must be faced by people with hemoglobinopathy such as thalassemia. In Indonesia, the prevalence of patient with thalassemia is fairly high. To overcome the conditions of iron overload, iron chelator is needed. However, the available iron chelator therapy has many weaknesses. Therefore, a study of Mangiferin that has an iron chelator effect, has been conducted. However, the bioavailability of mangiferin is low so it needs to be formed as nanoparticles and wrap in chitosan-alginate. In previous studies, the mangiferin effect on MDA levels in the heart of rats with excess iron has not been measured Objective: This study aims to assess the ability of mangiferin and mangiferin in chitosan- alginate nanoparticles on MDA levels in the heart of rats with iron overload conditions. Method: Twenty-five Sprague-Dawley rats were divided into five groups: control (N), iron overload rats (IO), and an oral therapy group, IO rats treated with mangiferin 50 mg/kg/day per oral (IO+M50), mangiferin chitosan-alginate nanoparticle 50 mg/kg/day (IO+MN50), and mangiferin chitosan-alginate nanoparticle 25 mg/kg/day (IO+MN25).The rats were given Iron Dextran 15 mg intraperitoneal, twice a week for four weeks. MDA levels are measured in heart organs using a spectrophotometer. Result: The MDA concentration in heart at N, IO, MN, MN50, and MN25 groups were 7,36 nMol/mg, 2,53 nMol/mg, 5,64 nMol/mg, 4,80 nMol/mg, and 9,36 nMol/mg. There was no decline in MDA levels in the IO group compare to therapy group. However, there was a significant difference in MDA levels of the Sprague-Dawley mouse heart tissue in each group (ANOVA, P = 0.048). It was also found a significant difference between the IO group and MN (p = 0.03) and MN 50 (p = 0.041). Conclusion: Mangiferin and mangiferin in chitosan-alginate nanoparticles could not reduce MDA levels in the heart of mice with iron overload."

"Latar belakang : Toluena merupakan zat pelarut sering digunakan di berbagai industri seperti dalam pembuatan cat, lem dan lainnya. Toluena mempunyai sifat lipofilik dan memberikan efek toksik ke beberapa organ seperti sistem saraf pusat. Pada tahap biomolekuler, toluena merubah struktur lipid pada membran sel, sehingga terjadi peningkatan kadar MDA plasma dan jaringan. Pada Sistem Saraf Pusat, toluena bisa melewati sawar otak dan menyebabkan gangguan pada serebelum otak sehingga dapat meningkatkan kadar MDA serta terjadi perubahan struktur pada dinding sel astrosit. Metode : Untuk mengetahui efek pajanan toluena selama 14 hari dengan dosis dibawah nilai ambang pada organ serebelum otak, dan dilakukan pemeriksaan kadar MDA serebelum otak, serta kerusakan dari sel Astrosit, menggunakan lima kelompok tikus jenis Wistar jantan dengan pajanan sebesar 1,6 ml; 3,2 ml; 6,4 ml; 12,8 ml; dan kelompok kontrol tanpa pajanan. Hasil: Analisis uji nilai kadar MDA serebelum otak menggunakan One Way Anova dengan hasil tidak ada perbedaan rerata (p=0.133) antar kelompok pajanan dengan kelompok kontrol, dan analisis jumlah sel Astrosit dengan menggunakan One Way Anova didapatkan (p=0,310) dengan hasil tidak ada perbedaan antar kelompok pajanan. Kesimpulan : Tidak ada perbedaan rerata pada kelompok pajanan pada nilai MDA serebelum Otak maupun jumlah Sel Astrosit yang terpajan toluena dengan dosis dibawah nilai ambang.

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Backgrounds : Toluene is a solvent commonly used in various industries such as in the manufacture of paint, glue and others. Toluene has lipophilic properties and toxic effects to some organs such as the central nervous system. At this stage of biomolecular, toluene alters the structure of the lipids in cell membranes, resulting in an increased of plasma and tissue levels of MDA. In the Central Nervous System, toluene can cross the blood brain barrier and cause a disruption in the cerebellum of the brain, thereby increasing the levels of MDA and structural changes in the structure of astrocytes’ cells.

Methods : To determine the effect of toluene exposure for 14 days at doses below the threshold value on the organ brain cerebellum and cerebellar MDA examination of the brain, as well as causing damage to Astrocytes cells, using five groups of male Wistar rats with four types of exposure of 1.6 ml; 3.2 ml; 6.4 ml; 12.8 ml; and a control group without exposure.

Results : MDA value analysis test brain cerebellum using One Way Anova showed no significance mean difference (p = 0.133) between the exposed group and the control group. From the analysis of the number of cells Astrocytes using One Way Anova that obtained (p = 0.310) with no difference in outcomes among exposed groups.

Conclusion : There was no significance difference in the group mean exposure to MDA values and the number of cells of the cerebellum Brain Astrocytes exposed to toluene at a dose below the threshold value."

"Torsio testis merupakan kedaruratan dalam urologi yang dapat terjadi pada 1 dari 4000 laki-laki berusia dibawah 25 tahun, dan apabila keadaan ini tidak segera ditangani dengan benar dalam 4 sampai 6 jam dapat terjadi nekrosis testis. Dari penelitian sebelumnya didapatkan torsio testis dengan puntiran sebesar 720° dan lama puntiran lebih dari 4 jam dapat menyebakan kerusakan testis secara menetap. Oleh karena itu tindakan bedah sedini mwtgkin harus dilakukan untuk menyelamatkan testis dari kerusakan menetap, saat ini tindakan bedah yang dianjurkan adalah melakukan detorsi testis dan orkidopeksi bilateral. Tindakan ini dilaporkan dapat menyelamatkan testis sampai dengan 90%, namun dalam pengamatan yang lebih lanjut menunjukkan lebih dari 67% tetstis tersebut akan mengalami atropi dan menjadi subfertil. Menurut Hagan dan kawan-kawan dari 55 pasien yang diamati hanya 7 pasien yang menenjukkan spermiogrnmnya normal Oleh karena itu dibutuhkan suatu terobosan lain dalam penatalaksanaan torsio testis guna menekan angka terjadinya kerusakan testis permanen secara signifikan. Kerusakan jaringan testis akibat torsio testis disebakan adanya ischemia yang diperberat dengan teijadinya reperfosion injury (IR) setelah dilakukan detorsi. Telah banyak penelitian dilakukan untuk mengetahui mekanisme dan penanganan IR., diantaranya penggunaan oksigen hiperbarik yang secara signifikan dapat mengurangi efek IR dalam tindakan pembuatan flap kulit dan otot yang percobaannya dilakukan pada binatang.

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Testicular torsion is a urological emergency that can occur in 1 in 4000 men under 25 years of age, and if this condition is not treated properly within 4 to 6 hours, testicular necrosis can occur. From previous research, it was found that testicular torsion with a twist of 720° and a twisting time of more than 4 hours can cause permanent testicular damage. Therefore, surgical action must be carried out as early as possible to save the testicles from permanent damage. Currently, the recommended surgical treatment is testicular detorsion and bilateral orchidopexy. This action was reported to be able to save up to 90% of the testicles, but further observations showed that more than 67% of the testicles would experience atrophy and become subfertile. According to Hagan and friends, of the 55 patients who were observed, only 7 patients showed normal sperm. Therefore, another breakthrough is needed in the management of testicular torsion in order to significantly reduce the rate of permanent testicular damage. Damage to testicular tissue due to testicular torsion is caused by ischemia which is exacerbated by the occurrence of reperfusion injury (IR) after detorsion. Many studies have been carried out to determine the mechanism and treatment of IR, including the use of hyperbaric oxygen which can significantly reduce the effects of IR in the procedure of creating skin and muscle flaps in experiments carried out on animals."

"ABSTRAKLatar Belakang: Mangiferin diketahui memiliki aktivitas sebagai agen pengikat besi, namun pemberian mangiferin melalui oral memiliki bioavailabilitas yang rendah. Sistem hantaran dengan nanopartikel diharapkan dapat meningkatkan bioavailabilitas dan efektivitas mangiferin. Penelitian bertujuan menguji efektivitas mangiferin nanopartikel kitosan-alginat dalam menurunkan kadar besi di plasma dan organ, kadar ferritin, transferrin, SGOT dan SGPT. Metode: Penelitian menggunakan desain eksperimental in vivo dengan hewan coba tikus Sprague-Dawley dibagi dalam 5 kelompok, yaitu kelompok normal, kelebihan besi, terapi mangiferin 50 mg/KgBB, terapi mangiferin dalam nanopartikel kitosanalginat 25 mg/KgBB, dan terapi mangiferin dalam nanopartikel kitosan-alginat 50 mg/KgBB. Pengukuran kadar Fe plasma, hati dan jantung, kadar Ferritin, kadar Transferrin, dan nilai aktivitas SGPT dan SGOT. Hasil: Kadar besi plasma, besi hati dan jantung, ferritin, dan transferrin pada kelompok kelebihan besi adalah 45,52 mg/L; 3661,98 μg/gram; 1734,4 μg/gram; 3578,16 ng/mL; 388,96 μg/dL, sedangkan pemberian terapi mangiferin 50 mg/KgBB (p < 0,05) menghasilkan 5,17 mg/L; 1572,96 μg/gram; 776,68 μg/gram; 1136,51 ng/mL; 272,18 μg/dL, pemberian terapi mangiferin dalam nanopartikel kitosan-alginat 25 mg/KgBB (p < 0,05) menghasilkan 5,74 mg/L; 1090,01 μg/gram; 753,90 μg/gram; 520,89 ng/mL; 231,97 μg/dL, pemberian terapi mangiferin dalam nanopartikel kitosan-alginat 50 mg/KgBB (p < 0,05) menghasilkan 3,34 mg/L; 1703,92 μg/gram; 759,2 μg/gram; 559,48 ng/mL; 235,70 μg/dL. Tidak terdapat perbedaan bermakna antar kelompok terhadap nilai aktivitas SGOT dan SGPT Kesimpulan: Mangiferin dalam nanopartikel kitosan-alginat efektif menurunkan kadar besi, ferritin, transferrin plasma, dan kadar besi di organ hati dan jantung, namun tidak menurunkan nilai aktivitas SGOT dan SGPT. Efektivitas mangiferin dalam nanopartikel kitosan-alginat tidak berbanding lurus dengan dosis.

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ABSTRACTBackground: Mangiferin was known to have activity as an iron-chelating agent, but oral administration of mangiferin has poor bioavailability. Nanoparticles delivery system is expected to increase bioavailability and effectiveness of mangiferin. This study aims to examine the effectiveness of mangiferin in chitosanalginate nanoparticles in reducing iron levels in plasma and organs, ferritin, transferrin, SGOT and SGPT activities. Methods: This is an in vivo experimental study using Sprague-Dawley rats, divided into 5 groups, normal, iron overload, mangiferin 50mg/KgBW, mangiferin in chitosan-alginate nanoparticles 25mg/KgBW, and mangiferin in chitosanalginate nanoparticles 50mg/KgBW. Fe levels were measured in plasma, liver and heart. In addition ferritin levels, transferrin levels, and SGPT and SGOT activities also measure at day 29th. Results: Plasma iron levels, liver and heart iron levels, ferritin, and transferrin in the iron overload group were 45.52 mg/L; 3661.98 μg/gram; 1734.4 μg/gram; 3578.16 ng/mL; 388.96 μg/dL, treatment with mangiferin 50 mg/KgBW (p < 0.05) reduced those parameters to 5.17 mg/L; 1572.96 μg/gram; 776.68 μg/gram; 1136.51 ng/mL; 272.18 μg/dL, treatment with mangiferin in chitosan-alginate nanoparticles 25 mg/KgBW (p < 0.05) reduced those parameters 5.74 mg/L; 1090.01 μg/gram; 753.90 μg/gram; 520.89 ng/mL; 231.97 μg/dL, treatment with mangiferin in chitosan-alginate nanoparticles 50 mg/KgBW (p < 0.05) reduced those parameters 3.34 mg/L; 1703.92 μg/gram; 759.2 μg/gram; 559.48 ng/mL; 235.70 μg/dL. There is no significant difference in SGOT and SGPT activities. Conclusions: Mangiferin in chitosan-alginate nanoparticles was effective in preventing the increase of iron, ferritin, transferrin plasma levels, and iron levels in the liver and heart, but not prevent the increasing of SGOT and SGPT. The effectiveness of mangiferin in chitosan-alginate nanoparticles is not directly proportional to the dose."