Potential Hepatoprotective Effects of Adenosine Triphosphate Against Olaparib-Induced Oxidative Liver Injury: An Experimental Rat Model
DRUG DESIGN, DEVELOPMENT AND THERAPY, cilt.20, sa.6, ss.1-17, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 20 Sayı: 6
- Basım Tarihi: 2026
- Doi Numarası: 10.2147/dddt.s613667
- Dergi Adı: DRUG DESIGN, DEVELOPMENT AND THERAPY
- Derginin Tarandığı İndeksler: Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Scopus, Science Citation Index Expanded (SCI-EXPANDED), BIOSIS, EMBASE, MEDLINE, Directory of Open Access Journals
- Sayfa Sayıları: ss.1-17
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Erzincan Binali Yıldırım Üniversitesi Adresli: Evet
Özet
Background: Olaparib, a clinically established poly (ADP-ribose) polymerase (PARP) inhibitor widely used in oncology, has significantly improved outcomes in several malignancies. However, increasing evidence indicates that olaparib may induce hepatocellular injury through mechanisms involving oxidative stress, inflammation, and mitochondrial dysfunction. Adenosine triphosphate (ATP), a key regulator of cellular bioenergetics and redox homeostasis, may confer protection against oxidative tissue injury. This study investigated the hepatoprotective effects of ATP against olaparib-induced oxidative liver damage in rats and compared its efficacy with melatonin.
Methods: Twenty-four male albino Wistar rats were randomly assigned to four experimental groups (n = 6): healthy control (HG), olaparib-treated (OLP), ATP plus olaparib (ATOL), and melatonin plus olaparib (MLOL). Olaparib was administered at a dose of 100 mg/kg orally twice daily, whereas ATP (5 mg/kg, intraperitoneally) and melatonin (10 mg/kg, orally) were administered once daily. The treatments were administered for 14 consecutive days. Hepatic oxidative and inflammatory status was assessed by measuring malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), interleukin-6 (IL-6) and ATP levels in liver tissue. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured as biochemical indicators of hepatocellular injury. Liver tissues were also examined histopathologically.
Results: Olaparib administration significantly increased hepatic MDA and IL-6 levels together with serum ALT and AST activities, while significantly reducing hepatic tGSH and ATP levels and SOD and CAT activities compared with the healthy group (p < 0.001). Both ATP and melatonin significantly attenuated these alterations (p < 0.001). Notably, ATP demonstrated a more pronounced protective effect than melatonin, particularly in suppressing aminotransferase elevations and improving histopathological liver architecture.
Conclusion: ATP significantly alleviates olaparib-induced hepatotoxicity by attenuating oxidative stress, suppressing inflammatory responses, restoring antioxidant defense mechanisms and significantly replenishing depleted hepatic ATP levels. These findings suggest that ATP may represent a promising therapeutic strategy for preventing PARP inhibitor-associated drug-induced liver injury. The diagram illustrates a study on olaparib-induced hepatotoxicity. Olaparib is administered orally twice daily, leading to hepatotoxicity in a rat model. Adenosine triphosphate is given intraperitoneally once daily and melatonin is given orally once daily. The study includes four groups: Healthy (n=6), Olaparib-alone (100 mg/kg) (n=6), ATP (5 mg/kg) plus Olaparib (100 mg/kg) (n=6) and Melatonin (10 mg/kg) plus Olaparib (100 mg/kg) (n=6). Liver tissue analysis includes measurements of malondialdehyde, total glutathione, superoxide dismutase, catalase, interleukin 6 and adenosine triphosphate for all groups (n=6). Histopathology is performed for all groups (n=6). Blood serum analysis includes alanine transaminase and aspartate transaminase for all groups (n=6).Study: olaparib hepatotoxicity, ATP/melatonin treatments, liver tissue & serum analysis.