[ABSTRAK
Doksorubisin 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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ABSTRACT
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, 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]