Apocynin may alleviate side effects of autophagy-blocked radiotherapy through antioxidant effects.

Abstract

One of the most widely used techniques for cancer treatment is radiotherapy. Autophagic pathways allow some cancer cells that are resistant to radiation therapy to survive. Inhibiting autophagy has been shown to improve radiotherapy efficacy in several cancer types. Chloroquine (CQ) is a reasonable choice that has been used for many years to treat malaria and is preferred because of its minimal side-effects. Nevertheless, the effects of coadministration of CQ with radiation on various tissues remain unclear. In this study, it was aimed to understand how CQ, used to increase the effectiveness of radiotherapy, has effects on small intestine tissue alone and together with radiotherapy and what role apocynin (APO) can play with its antioxidant character in these stress conditions. Animals were divided into eight groups. The control group received physiological saline, while the other groups received 8 Gy total body irradiation, 50 mg/kg CQ, and 20 mg/kg APO, alone and in combination. In addition to causing significant histological damage, radiation triggered autophagy and showed antiproliferative and apoptotic effects. CQ administered with radiotherapy (RAD) had antiproliferative effects and did not cause a significant change in apoptosis. Reduced glutathione level, glutathione reductase, glutathione peroxidase, glutathione S-transferase, catalase, superoxide dismutase activities, and total antioxidant status were decreased, while lipid peroxidation, total oxidant status, reactive oxygen species, tumor necrosis factor-α, nitric oxide levels, adenosine deaminase, alkaline phosphatase, trypsin, lactate dehydrogenase, sodium potassium ATPase, xanthine oxidase activities, and protein carbonyl contents were increased in the RAD, CQ, and RAD+CQ groups. Apocynin therapy reversed these effects.