Glabridin attenuates dibutyl phthalate-induced testicular toxicity via regulating oxidative stress, inflammation, apoptosis, and Wnt/β-catenin pathway

Tissue Cell. 2025 Nov 10;98:103223. doi: 10.1016/j.tice.2025.103223. Online ahead of print.

ABSTRACT

Dibutyl phthalate (DBP) is a member of phthalate esters which are considered as potent environmental toxicant owing to their damaging effects on different organs including testis. Glabridin (GLN) is a polyphenolic substance that is found in the roots of Glycyrrhiza glabra and exhibits a wide range of pharmacological activities. This research investigation explored the ameliorative potential of GLN against DBP instigated testicular toxicity. Forty-eight male Sprague Dawley rats were categorized into control, DBP (200 mg/kg), DBP (200 mg/kg) + GLN (50 mg/kg), and GLN (50 mg/kg) group. We found that DBP administration exacerbated the gene expression of β-catenin, WNT1, and TCF7L2 while suppressed the gene expression of APC, AXIN1 as well as GSK3β. Furthermore, DBP exposure promoted the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) while suppressing the activities of superoxide dismutase (SOD), heme oxygenase-1 (HO-1), glutathione reductase (GSR), glutathione Peroxidase (GPx), catalase (CAT), and glutathione (GSH). Moreover, DPB administration exacerbated Caspase-9, Bax and Caspase-3 while diminishing Bcl-2 concentrations. A notable escalation was observed in the levels of interleukin-6 (IL-6), tumor necrosis factor- α (TNF-α), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and nuclear factor- kappa B (NF-κB) following the administration of DBP. Besides, DBP intoxication distorted the normal morphology of testicular tissues. Nonetheless, GLN therapy significantly alleviated testicular impairments via regulating aforementioned biochemical and histological abnormalities. These findings suggest he palliative efficacy of GLN against DPN induced testicular damages thereby recommending the use of GLN to promote reproductive health in male.

PMID:41240790 | DOI:10.1016/j.tice.2025.103223