Comparison of the protective effects of curcumin and caffeic acid phenethyl ester against doxorubicin‐induced testicular toxicity

Abstract

Testicular dysfunction is one of the serious side effects of cytotoxic chemotherapy. It has been reported that low sexual function and quality of life and infertility concerns associated with gonadal insufficiency in young patients are related to psychosocial distress (Levi et al., 2015). Doxorubicin (DOX, brand name Adriamycin), which is one of the most important cornerstones of many chemotherapeutic protocols, is an anticancer drug selected in the treatment of many chemo-responsive tumours from ovarian, breast, liver and lung cancer and lymphomas. However, DOX can cause severe dose-dependent toxicity for other nontarget tissues, including testicular tissues (e.g. reduced testicular weight; Nishi et al., 2018). Studies have reported that DOX toxicity causes testicular damage and apoptosis and adversely affects reproductive function (Kopalli et al., 2016; Nowrouzi et al., 2019). In addition, DOX has been reported to increase oxidative stress by reducing antioxidant capacity in testicular tissue (Uyeturk et al., 2014). Does DOX cause testicular toxicity by only increasing oxidative stress and apoptosis? Or does DOX have an effect on testicular

Nano-Curcumin Prevents Copper Reproductive Toxicity by Attenuating Oxidative Stress and Inflammation and Improving Nrf2/HO-1 Signaling and Pituitary-Gonadal Axis in Male Rats

“…Exposure to Cu compounds has been associated with adverse effects, including testicular oxidative stress, and apoptosis, along with declined sperm quality [ 19 , 24 ]. CUR has shown potent antioxidant properties and protected the testis against injury induced by various agents [ 26 , 27 , 41 , 42 , 43 ]. Herein, we evaluated the role of CUR and N-CUR in attenuating CuSO 4 -induced testicular injury in rats, pointing to changes in steroidogenesis, Nrf2/HO-1 signaling, and inflammatory and apoptosis markers.…”

“…Although the effect of CuSO 4 on spermatogenesis has been previously reported [ 19 ], we introduced evidence that it downregulates AR in the testis and that CUR and its nanoform can increase testosterone biosynthesis and AR. The ability of CUR to prevent testicular damage caused by various toxicants, including titanium dioxide [ 41 ], lead [ 42 ], and DOX [ 43 ] has been previously demonstrated. In these studies, the protective effect of CUR prevented histopathological alterations, increased testosterone release and enhanced sperm parameters.…”

“…The well-documented antioxidant and radical-scavenging properties of CUR [ 32 , 33 , 38 , 67 ] are involved in its protective effect against CuSO 4 -induced testicular toxicity. The antioxidant potency of CUR was demonstrated in animal models of testicular toxicity induced by lead acetate [ 42 ], and DOX [ 43 ] where it decreased MDA and enhanced GSH and antioxidant enzymes. In this study, N-CUR decreased MDA and NO, and boosted antioxidant defenses in the testis of CuSO 4 -administered rats significantly as compared to the native form, demonstrating its enhanced radical-scavenging activity.…”

“…CUR has been evidenced to act in a multi-targeted fashion through its ability to target bioactive proteins in various signaling pathways or its epigenetic modulating power [ 39 , 40 ]. The protective efficacy of CUR against testicular injury induced by titanium dioxide [ 41 ], lead acetate [ 42 ], and doxorubicin (DOX) [ 43 ] has been reported; however, its protective efficacy against testicular injury caused by CuSO 4 has not been investigated yet. In addition, the rapid metabolism and poor systemic bioavailability of CUR are the main drawbacks that can limit its therapeutic applications [ 44 ].…”

Ginger reserves testicular spermatogenesis and steroidogenesis in difenoconazole‐intoxicated rats by conducting oxidative stress, apoptosis and proliferation

“…In this respect, caffeic acid can suppress testicular oxidative injury‐induced apoptosis by blocking the increases in matrix metalloproteinases and pro‐inflammatory cytokines. It can also increase sperm quality by enhancing the mitochondrial membrane components and providing the spermatozoa with exogenous energy (Huyut et al., 2021). This energy can be utilised by mitochondria to give high mitochondrial membrane potential with the low plasma membrane and acrosome integrity rates which protect the spermatogenesis process from any disturbance (Gungor et al., 2019).…”