Neuroprotective effects of [Gly14]-Humanin against cisplatin-induced neurotoxicity: evidence from in vitro and in vivo studies

Cisplatin is a widely used chemotherapeutic agent whose clinical use is limited by dose-dependent adverse effects, particularly neurotoxicity. [Gly14]-Humanin, a potent analogue of the endogenous peptide Humanin, has been reported to possess marked neuroprotective properties. This study evaluated the protective effects of [Gly14]-Humanin against cisplatin-induced neurotoxicity using complementary in vitro and in vivo models. Primary rat neuronal cultures were exposed to cisplatin (50 and 100 µM) and treated with [Gly14]-Humanin (1, 5, or 7.5 µM). In vivo, male Balb/c mice were assigned to six groups (n = 10/group), and [Gly14]-Humanin (3 or 6 mg/kg/day, i.p.) was administered for 14 days, with a single cisplatin dose (10 mg/kg, i.p.) on day 10. Cell viability, oxidative stress, inflammatory and apoptosis-related markers, and Hoechst 33342 staining were assessed in neuronal cultures, while brain tissues were evaluated biochemically, molecularly, histopathologically, and immunohistochemically.Cisplatin significantly increased oxidative stress, inflammation, and apoptosis (p < 0.05). In contrast, [Gly14]-Humanin preserved cell viability and antioxidant status, reduced pro-inflammatory cytokine and caspase-3/caspase-9 mRNA expression, increased the Bcl-2/Bax ratio, and attenuated histopathological and immunohistochemical alterations (p < 0.05). Collectively, these findings suggest that [Gly14]-Humanin exerts neuroprotective effects against cisplatin-induced neuronal injury through attenuation of oxidative stress, inflammatory responses, and apoptosis-related changes. Not applicable.