Electronic Theses and Dissertation

Hepatoksisitas akibat obat kemoterapi seperti doksorubisin merupakan komplikasi serius yang dapat menyebabkan kerusakan struktural dan fungsional hati. Sekretom sel punca mesenkimal (MSC-secretome) diketahui memiliki potensi immunomodulator dan regeneratif melalui mekanisme parakrin, sehingga berpeluang digunakan sebagai terapi non-seluler pada kerusakan hati. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian sekretom MSC secara preventif dan kuratif terhadap hepatosomatic indeks (HSI) dan gambaran histopatologi hati tikus model hepatotoksik. Penelitian ini merupakan penelitian eksperimental laboratorium dengan desain posttest only control group menggunakan hati tikus putih (Rattus norvegicus) galur wistar. Tikus dibagi menjadi empat kelompok : kontrol sehat (KN), kontrol hepatotoksik (KP), sekretom MSC preventif (P1) dan sekretom MSC kuratif (P2). Hepatotoksisitas diinduksi dengan doksorubisin 10 mg/kgBB dosis tunggal intraperitoneal. Sedangkan sekretom MSC 0,15 ml intravena diberikan segera setelah DOX (P1) dan pada hari ke-5 setelah DOX (P2). Nilai HSI dan histopatologis hati dianalisis secara statistik. Hasil penelitian menunjukkan bahwa pemberian sekretom MSC baik secara preventif maupun kuratif belum menurunkan nilai HSI secara signifikan. Namun secara histopatologis, kelompok kuratif menunjukkan kecendrungan penurunan derajat degenerasi dan nekrosis hepatosit meskipun tidak berbeda signifikan secara statistik. Penelitian ini menyimpulkan bahwa sekretom MSC memiliki potensi respon perbaikan jaringan hati secara histopatologis, sementara perubahan makroskopis HSI belum terdeteksi dalam durasi penelitian ini.

Kata Kunci : sekretom sel punca mesenkimal, hepatotoksisitas, hepatosomatic index, histopatologi hati, doksorubisin.

Drug-induced hepatotoxicity caused by chemotherapeutic agents such as doxoru-bicin is a serious complication that may lead to structural and functional liver damage. Mesenchymal stem cell secretome (MSC secretome) possesses immuno-modulatory and regenerative properties through paracrine mechanisms, making it a potential non-cellular therapeutic approach for liver injury. This study aimed to evaluate the effects of preventive and curative administration of MSC secre-tome on the hepatosomatic index (HSI) and liver histopathological features in a rat model of hepatotoxicity. This experimental laboratory study employed a post-test-only control group design using Wistar rats (Rattus norvegicus). The animals were divided into four groups: healthy control (KN), hepatotoxic control (KP), preventive MSC secretome group (P1), and curative MSC secretome group (P2). Hepatotoxicity was induced by a single intraperitoneal injection of doxorubicin at a dose of 10 mg/kg body weight. MSC secretome (0.15 mL, intravenous) was administered immediately after doxorubicin injection in the preventive group (P1) and on day 5 after doxorubicin administration in the curative group (P2). HSI values and liver histopathological findings were analyzed statistically. The results showed that neither preventive nor curative administration of MSC secre-tome significantly reduced HSI values. However, histopathological evaluation indicated that the curative group tended to exhibit lower degrees of hepatocyte degeneration and necrosis, although these differences were not statistically sig-nificant. This study concludes that MSC secretome demonstrates potential histo-pathological liver tissue repair, while macroscopic changes in HSI were not de-tected within the duration of this study. Keywords: mesenchymal stem cell secretome, hepatotoxicity, hepatosomatic in-dex, liver histopathology, doxorubicin.