Harmine reduces ROS-mediated hepatotoxicity in a cisplatin mouse model.
Cisplatin, a widely used anticancer agent, has adverse effects on normal tissues during cancer treatment. This study aimed to investigate the use of harmine, a plant β-carboline alkaloid, against pathways associated with ROS-induced apoptosis in the livers of mice administered wi
- Authors
- Jalili C, Akhshi N, Mohebi H, Zamir-Nasta T, Tabandeh MR, Esmaeli M, Ravankhah S, Ghanbari A
- Journal
- Research in pharmaceutical sciences
- Published
- 2026-08-01
- DOI
- 10.4103/rps.rps_194_25
- PMID
- 42559493
- Content type
- Paper
- Authority
- Academic
Abstract
Cisplatin, a widely used anticancer agent, has adverse effects on normal tissues during cancer treatment. This study aimed to investigate the use of harmine, a plant β-carboline alkaloid, against pathways associated with ROS-induced apoptosis in the livers of mice administered with cisplatin. Twenty-four male Balb/c mice were randomly assigned to four groups (n = 6): (1) control group received daily intraperitoneal injections of saline for four days, (2) harmine group (15 mg/kg, intraperitoneally, daily for 4 days), (3) cisplatin group (5.5 mg/kg, intraperitoneally, one injection), and (4) cisplatin + harmine co-administration group. After sacrificing the animals under deep anesthesia, blood and liver tissue samples were collected for biochemical and molecular experiments. Cisplatin significantly elevated histopathological criteria (both qualitative and quantitative), levels of enzyme activity, malondialdehyde, nitric oxide, ROS, and apoptosis, and decreased glutathione, superoxide dismutase, and total antioxidant capacity. However, these factors were improved in the co-administration group compared to the cisplatin group. Furthermore, cisplatin treatment significantly upregulated caspase-8, BAX, p53, caspase-3, TNF-α, and NF-κB gene expression, while downregulating BCL-2. Co-administration with harmine led to significant changes in gene expression relative to the cisplatin group. Cisplatin notably increased protein levels of caspase-8, BAX, and TNF-α, but these levels were significantly reduced in the co-treatment group. Harmine effectively ameliorates cisplatin-induced hepatitis by suppressing ROS production, thereby reducing intrinsic, extrinsic, and inflammation-induced apoptosis. These findings suggest that the antioxidant and anti-inflammatory properties of Harmine play a key role in its hepatoprotective actions.
Citation
Jalili C, Akhshi N, Mohebi H, Zamir-Nasta T, Tabandeh MR, Esmaeli M, Ravankhah S, Ghanbari A (2026) Harmine reduces ROS-mediated hepatotoxicity in a cisplatin mouse model.. Research in pharmaceutical sciences. doi:10.4103/rps.rps_194_25
Indexed by the DMT Code Research Bibliography, an open, stance scored library (CC-BY-4.0).