POTENSI HEPATOPROTEKTIF EKSTRAK Piper betle TERHADAP EKSPRESI mRNA ENZIM ANTIOKSIDAN SOD-1 DAN CATALASE SERTA APOPTOSIS BAX PADA TIKUS MODEL ISCHEMIA REPERFUSION INJURY

Zhafira Mafaz, dr. Nur Arfian, Ph.D., dr. Ratih Yuniartha, Ph.D., Dr. dr. Muhammad Mansyur Romi, SU., PA(K)

2025 | Skripsi | PENDIDIKAN DOKTER

Latar Belakang 

Hepatic ischemia-reperfusion injury (IRI) adalah penyebab utama morbiditas dan mortalitas setelah transplantasi hepar. Hepatic IRI adalah pemulihan aliran darah ke jaringan yang sebelumnya iskemia yang menyebabkan cedera berkepanjangan. Ekstrak Piper betle telah diketahui dapat menghambat reactive oxygen species dan sekresi sitokin pro-inflamasi. Meskipun demikian, belum ada penelitian tentang aktivitas ekstrak P. betle pada model hepatic IRI. Oleh karena itu, penelitian ini bertujuan untuk mengetahui aktivitas ekstrak P. betle terhadap fungsi hepar, enzim antioksidan, dan apoptosis model hepatic IRI.

Metode 

Ekstrak P. betle diekstrasi dengan metode ultrasonic-assisted extraction menggunakan etanol 80%. Hepatic IRI diinduksi pada tikus Wistar jantan (2 bulan, 130-200 g) dengan menjepit trias porta selama 60 menit, diikuti reperfusi selama 3 hari. Selama reperfusi, ekstrak P. betle dosis 100, 200, dan 400 mg/kg diberikan secara oral sekali sehari. Fungsi hepar dinilai berdasarkan kadar serum alanine aminotransferase (ALT). Histologi jaringan hepar diamati dengan pewarnaan hematoksilin-eosin (HE). Ekspresi Bax, superoxide dismutase-1 (SOD-1), dan catalase diukur dengan reverse transcription-polymerase chain reaction (RT-PCR). 

Hasil  

Tikus yang diberi ekstrak P. betle menunjukkan kadar serum ALT yang lebih rendah (p<0>P. betle menghasilkan perbaikan histologi hepatosit. Ekspresi mRNA Bax sebagai penanda apoptosis pada kelompok ekstrak P. betle juga lebih rendah (p<0> hepatic IRI. Ekstrak P. betle menunjukkan ekspresi mRNA enzim antioksidan yang lebih tinggi dibandingkan kontrol hepatic IRI, yaitu SOD-1 (p<0>P. betle lainnya. 

Kesimpulan 

Dengan demikian, ekstrak P. betle mempunyai aktivitas hepatoprotektif terhadap hepatic IRI dengan menginduksi ekspresi enzim antioksidan dan menghambat peningkatan mediator apoptosis.

Background 

Hepatic ischemia-reperfusion injury (IRI) is the leading cause of morbidity and mortality following liver transplantation. Hepatic IRI is defined as the restoration of blood flow to previously ischemic tissues which leads to prolonged injury. Piper betle extract has been studied to inhibit reactive oxygen species and proinflammatory cytokines production. However, the effect of P. betle extract in hepatic IRI has not been elucidated yet. This study aimed to determine the activity of P. betle extract in attenuating liver function, antioxidant enzyme, and apoptosis in hepatic IRI. 

Method 

P. betle extract was prepared by ultrasonic-assisted extraction using 80% ethanol. Hepatic IRI was performed in male Wistar rats (2 months, 130-200 g) by clamping the portal triad for 60 minutes, followed by 3 days of reperfusion. During reperfusion, P. betle extract doses of 100, 200, and 400 mg/kg were orally administered once daily. Liver function was assessed by serum level of alanine aminotransferase (ALT). The histology of the liver tissue was observed by hematoxylin-eosin (HE) staining. The expression of Bax, superoxide dismutase-1 (SOD-1), and catalase were measured by reverse transcription-polymerase chain reaction (RT-PCR).  

Results 

The rats given P. betle extract showed significantly lower serum ALT levels (p<0> P. betle extract led to improvements in hepatocyte histology. The expression of mRNA Bax, a marker of apoptosis, was also lower (p<0>P. betle extract group compared to the hepatic IRI control group. P. betle extract demonstrated higher expression of antioxidant enzyme mRNA compared to the hepatic IRI control group, specifically SOD-1 (p<0>P. betle extract treatment groups, the SR-400 group exhibited the highest ameliorative effect. 

Conclusion 

In conclusion, P. betle extract has hepatoprotective activity for hepatic IRI by inducing expression of antioxidant enzymes and inhibiting elevation of apoptosis mediator.

Kata Kunci : Piper betle, hepatic ischemia-reperfusion injury, enzim antioksidan, dan apoptosis