ABSTRACT
Bortezomib is a chemotherapeutic agent used to treat several cancers; however, it exhibits severe side effects in testicular tissue. We investigated the use of agomelatine to prevent testicular tissue damage caused by bortezomib. We used 36 male Sprague-Dawley rats divided randomly into six equal groups: group 1, no treatment control; group 2, agomelatine treatment only; group 3, bortezomib treatment only for 48 h; group 4, bortezomib + agomelatine treatment for 48 h; group 5, bortezomib treatment only for 72 h; and group 6, bortezomib + agomelatine treatment for 72 h. After treatments, the rats were sacrificed and testicular tissue was harvested. Lipid oxidation (LPO) and superoxide dismutase (SOD) levels in the tissues were determined using biochemical methods. Tissue samples also were examined using histopathological and immunohistochemical techniques. The LPO level was increased, while the SOD level was decreased in the bortezomib treated groups. We found that agomelatine treatment normalized LPO and SOD activities in the bortezomib treated groups. In the spermatogonia and Sertoli cells, the staining density of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and caspase 3 were decreased in the bortezomib + agomelatine groups at both 48 and 72 h compared to bortezomib only treated groups. We observed maturation arrest, basal membrane thickening, increase in inflammatory cells and connective tissue, and edema between germ cells in the bortezomib only treated groups. By contrast, normal basal membrane, less edema and more normal maturation were observed in the bortezomib + agomelatine groups at 48 and 72 h. We found that agomelatine reduced the damaging effects of bortezomib. The use of agomelatine to prevent bortezomib induced testicular tissue damage in human patients should be investigated further.
Subject(s)
Acetamides/pharmacology , Bortezomib/toxicity , Testis/drug effects , Animals , Antineoplastic Agents/toxicity , Drug-Related Side Effects and Adverse Reactions/prevention & control , Immunohistochemistry , Male , Oxidative Stress/drug effects , Rats, Sprague-Dawley , Reference Standards , Superoxide Dismutase/metabolism , Testis/pathologyABSTRACT
BACKGROUND: Diabetes mellitus (DM) has a negative effect on cardiovascular functions. Little, however, is known of the overall effect of DM on the cardiac histology or the pathophysiological basis of this. AIM: We aimed to investigate the role of oxidative stress on the pathogenesis of diabetic cardiomyopathy in an experimental model. MATERIALS AND METHODS: 12 week-old female Sprague Dawley rats were randomly allocated into a healthy control group (n=6) and an DM group (n=6). After 12 weeks of alloxan induced DM, the groups' cardiac tissues were histopathologically analyzed and examined for determination of oxidant and antioxidant enzymes [activities of catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) and amount of reduced glutathione (GSH) and lipid peroxidation (LPO)]. RESULTS: When compared to the control group, the DM group showed cardiomyopathic changes. In the DM group, activities of CAT (144 +/- 0.9 vs. 112 +/- 1.4, p < 0.05) and LPO amount (27.0 +/- 0.74 vs. 14.4 +/- 0, 20, p < 0.05) were significantly increased whereas activities of SOD (142 +/- 0.2 vs. 146 +/- 0.7, p < 0.05) and amount of GSH (3.48 +/- 0.01 vs. 3.73 +/- 0.01, p < 0.05) were significantly decreased when compared to the control group. Besides, activities of MPO (7.3 +/- 0.02 vs. 8.6 +/- 0.11, p < 0.05) were comparable between groups. CONCLUSIONS: Using the experimental animal model, we were able to demonstrate that DM causes cardiomyopathic changes, and we propose that these changes could be mediated by an oxidative stress.