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Protective and restorative effects of hexarelin on MPTP-induced lung injury in mice
Onur Celikoglu1, Elif S Karanfil2, Ozlem Ozmen1
1Faculty of Veterinary Medicine Department of Pathology, Burdur Mehmet Akif Ersoy University, Burdur, Türkiye.
Objectives:
This study investigated the protective and therapeutic effects of hexarelin (HEX) against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced lung injury in mice by evaluating oxidative stress, IL-6-mediated inflammation, and Caspase-3-dependent apoptosis.
Methods:
Fifty male Balb/C mice were randomly assigned to five groups (n=10): control, MPTP, PREHEX, POSTHEX, and HEX. Parkinson-like neurotoxicity was induced by a single intranasal dose of MPTP (1 mg/kg). Hexarelin (10 μg/kg, i.p.) was administered twice at 4-h intervals before or after MPTP exposure. Lung tissues were examined histopathologically using hematoxylin-eosin staining, and immunohistochemically for Caspase-3, IL-6, and SOD expression.
Results:
MPTP caused severe pulmonary injury, including alveolar wall thickening, edema, hyperemia, and inflammatory infiltration, with increased Caspase-3 (p<0.001) and IL-6 (p=0.002) expression and reduced SOD immunoreactivity compared with controls (p<0.001). Both HEX regimens significantly reduced histopathological damage and improved immunohistochemical parameters (p<0.05). POSTHEX showed greater recovery than PREHEX, with lower apoptotic (p=0.005) and inflammatory (p=0.050) marker expression and higher SOD (p=0.007) levels. The enhanced efficacy of therapeutic post-treatment over prophylactic pretreatment is likely attributable to the active engagement of cytoprotective pathways during ongoing severe oxidative and inflammatory cascades, optimizing hexarelin's receptor-mediated cellular rescue mechanisms.
Conclusions:
Hexarelin demonstrated significant protective and therapeutic effects against MPTP-induced lung injury by mitigating oxidative stress, suppressing inflammation, and limiting apoptosis.
Insights
Hexarelin (HEX) protects against and treats lung injury caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by reducing oxidative stress, inflammation, and apoptosis.
Area of Science:
- Pulmonary Medicine
- Toxicology
- Pharmacology
Background:
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure induces significant lung injury.
- MPTP-induced lung injury is characterized by oxidative stress, IL-6-mediated inflammation, and Caspase-3-dependent apoptosis.
Purpose of the Study:
- To investigate the protective and therapeutic effects of hexarelin (HEX) on MPTP-induced lung injury in mice.
- To evaluate HEX's impact on oxidative stress, inflammation, and apoptosis markers in lung tissue.
Main Methods:
- Male Balb/C mice were exposed to MPTP (1 mg/kg, intranasal).
- Hexarelin (10 μg/kg, intraperitoneal) was administered either before (PREHEX) or after (POSTHEX) MPTP exposure.
- Lung tissues were analyzed for histopathological changes, Caspase-3, IL-6, and SOD expression.
Main Results:
- MPTP caused severe lung injury with increased Caspase-3 and IL-6, and decreased SOD.
- Both HEX treatment regimens (PREHEX and POSTHEX) significantly reduced lung damage and improved biochemical markers.
- Therapeutic POSTHEX treatment demonstrated superior recovery compared to prophylactic PREHEX treatment.
Conclusions:
- Hexarelin exhibits significant protective and therapeutic potential against MPTP-induced lung injury.
- HEX mitigates lung injury by reducing oxidative stress, suppressing inflammation, and limiting apoptosis.
- Therapeutic hexarelin administration is more effective than prophylactic treatment for MPTP-induced lung injury.
