Ellagic acid effects on testis, sex hormones, oxidative stress, and apoptosis in the relative sterility rat model following busulfan administration

Abstract

Background Busulfan is an antineoplastic medication that is broadly utilized for cancer treatment. It affects the testicular function and leads to sterility. The present study aimed to evaluate the effects of ellagic acid on testicular tissue changes, sexual hormones, antioxidant defense system, and caspase-9 and Bcl2 gene expression in the busulfan-induced relative sterile rat model. Methods This is an interventional-experimental animal study that was performed on 65 Adult male rats; they were randomly divided into five groups including control (1 ml of 0.9% normal saline), ellagic acid (50 mg/kg); busulfan (10 mg/kg); and busulfan plus ellagic acid (10 mg/kg and 50 mg/kg). At the end of the experiment, blood samples were collected, and plasma levels of sex hormones, antioxidant system, apoptosis-related genes, and testis histology were assessed. Results Busulfan reduced the levels of serum testosterone, total antioxidant capacity, gene expression of Bcl2, testicular volume, seminiferous tubule, germinal epithelium, interstitial tissue volume, and the number of spermatogonia, spermatocyte, round spermatid, elongated spermatid, Sertoli cells and Leydig cells (p < 0.05). Busulfan administration resulted in a significant increase (p < 0.05) in the level of LH, FSH, malondialdehyde, and caspase 9. Busulfan + ellagic acid (50 mg/kg) showed higher serum levels of testosterone, gene expression of Bcl-2 and antioxidant markers, and lower LH, FSH levels, and gene expression of caspase 9 compared to the Busulfan-treated rats (p < 0.05). Stereological parameters were also ameliorated in the group treated with Busulfan+ 50 mg/kg ellagic acid (p < 0.05). Conclusion In conclusion, the consumption of ellagic acid may have beneficial effects on the antioxidant defense system, sexual hormone abnormality, and testicular tissue damage induced by busulfan.

The effect of ellagic acid on rabbit sperm in vitro parameters after cryopreservation

“…Ceribasi et al (2012) indicated that this polyphenol not only exhibits antioxidant and antiapoptotic properties, but also it can chelate metal ions and, therefore, prevent ironand copper-catalyzed ROS generation. These and other authors reported a protective effect, when rats were treated with chemo-toxic compounds (Turk et al 2008;Ceribasi et al 2012;Rostami et al…”

Mesenchymal stromal/stem cells promote intestinal epithelium regeneration after chemotherapy-induced damage

“…Busulfan is an alkylating chemotherapeutic agent that prevents cell division [ 52 , 53 ]. However, its potential mechanism of action is very intricate and probably involves multiple biological processes, such as disruption of cellular redox equilibrium, proliferation, apoptosis, and autophagy [ 54 , 55 ]. We investigated short- and long-term busulfan-mediated damage and the corresponding MSC-mediated rescue of human small intestine epithelium in our co-culture system.…”

“…Our results demonstrate that long-term culture of small intestine organoids after treatment with busulfan decreases both the size and the number of organoids. The reduced number of organoids might be a consequence of an oxidative stress induction by busulfan [ 54 ], which results in a delayed increase in cell death. However, the late adverse effect of other pathways activated by busulfan cannot be excluded.…”

Mesenchymal stromal/stem cells promote intestinal epithelium regeneration after chemotherapy-induced damage

“…Busulfan is an alkylating chemotherapeutic agent that prevents cell division [48,49]. However, its potential mechanism of action is very intricate and probably involves multiple biological processes, such as disruption of cellular redox equilibrium, proliferation, apoptosis, and autophagy [50,51]. We investigated short-and long-term busulfan-mediated damage and the corresponding MSC-mediated rescue of human small intestine epithelium in our co-culture system.…”

“…Our results demonstrate that long-term culture of small intestine organoids after treatment with busulfan decreases both the size and the number of organoids. The reduced number of organoids might be a consequence of an oxidative stress induction by busulfan [50], which results in a delayed increase in cell death. However, the late adverse effect of other pathways activated by busulfan cannot be excluded.…”