Protective Effect of Lycopene on Ifosfamide-Induced Mitophagy through Pink, Parkin, and LC3-I/II Pathway in Testicular Tissue

نویسندگان

1 Faculty of Medicine, University of Al-Ameed, Karbala, Iraq

2 Division of Comparative Histology, Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

3 RASTA Specialized Research Institute (RSRI), West Azerbaijan Science and Technology Park (WASTP), Urmia, Iran

doi
10.22074/ijfs.2024.2036627.1740
چکیده

  Background: Ifosfamide (IFO) is a widely used chemotherapeutic agent that exerts cytotoxic effects through various mechanisms, including the induction of apoptosis and oxidative stress. However, its use is associated with detrimen­tal effects on male reproductive health, including mitochondrial dysfunction and oxidative stress-induced damage. Mitophagy, a selective autophagic process, plays a crucial role in maintaining mitochondrial homeostasis during spermatogenesis. This study aimed to investigate the potential protective effect of lycopene against IFO-induced mi­tophagy in testicular tissue. We evaluated the expression levels of key mitophagy regulators Pink1, Parkin, and LC3-I/ II in testicular tissue of rats treated with IFO alone or in combination with lycopene.Materials and Methods: In this experimental study, 24 mature male Wistar rats (250 g ± 25) were divided into control (received normal saline), IFO-sole (received 250 mg/kg, single dose, ip), lycopene (25 mg/kg, orally), and IFO+lycopene groups. Following 60 days, the rats were euthanized and the testicles were dissected out. The expression levels of Pink1, Parkin, and LC3-I/II were evaluated using qRT-PCR and immunohistochemistry (IHC) techniques.Results: Our findings demonstrated that IFO significantly upregulated Pink1, Parkin, and LC3-I/II expression at both mRNA and protein levels compared to controls. Conversely, lycopene administration mitigated these increases induced by IFO, suggesting its potential to attenuate IFO-induced mitophagy. Immunohistochemistry analysis con­firmed the protective effect of lycopene, showing reduced expression levels of Pink1, Parkin, and LC3-I/II in the presence of lycopene following IFO treatment.Conclusion: These results underscore lycopene's role as a potent protective agent that can mitigate IFO-induced mi­tophagy in testicular tissue. Further research into the underlying mechanisms of lycopene's protective effects will be crucial for developing therapeutic strategies to preserve male fertility during IFO treatment.

کلیدواژه‌ها