Morin provides therapeutic effect by attenuating oxidative stress, inflammation, endoplasmic reticulum stress, autophagy, apoptosis, and oxidative DNA damage in testicular toxicity caused by ifosfamide in rats

Objective(s): In the present study, it was evaluated whether morin has a protective effect on testicular toxicity caused by ifosfamide (IFOS), which is used in the treatment of various malignancies. Materials and Methods: For this purpose, ۱۰۰ or ۲۰۰ mg/kg morin was given to Sprague Dawley rats for ۲ days, and a single dose (۵۰۰ mg/kg) IFOS was administered on the ۲nd day. At the ۲۴th hr of IFOS administration, animals were decapitated and testicular tissues were taken and the status of oxidative stress, inflammation, endoplasmic reticulum stress (ERS), autophagy, and apoptosis markers were analyzed by biochemical, molecular, and histopathological methods.Results: According to the data obtained, it was determined that IFOS caused oxidative stress in testicular tissues. It was observed that inflammation, ERS, autophagy, apoptosis, and oxidative DNA damage occurred with oxidative stress. Morin treatment suppressed oxidative stress. Morin showed anti-inflammatory effects by reducing TNF-α and IL-۱β protein levels. It also increased the mRNA transcript levels of the ERS marker ATF-۶, PERK, IRE۱, GRP-۷۸, and CHOP genes, and the apoptosis marker genes Bax, Casp-۳, and apaf-۱. It up-regulated the anti-apoptotic protein Bcl-۲ gene and the cell survival signal AKT-۲ gene. Morin caused a decrease in beclin-۱ protein levels and showed an anti-autophagic effect. In addition, morin attenuated oxidative DNA damage and decreased ۸-OHdG immune-positive cell numbers.Conclusion: As a result, it was observed that IFOS caused cellular damage by activating various signaling pathways in testicular tissue, while morin exhibited protective properties against this damage.

Keywords:

Apoptosis , Ifosfamide , Inflammation , Morin , Oxidative stress , Testicular toxicity