Thymoquinone is a protective agent that reduces the negative effects of doxorubicin in rat testis

Abstract

Background: Doxorubicin (DOX) is used for treatment of many cancer types. Thymoquinone (THQ) is a powerful antioxidant agent used for reducing side effects of several drugs. The aim of this study is to determine possible therapeutic effects of THQ on doxorubicin-induced testicular toxicity in rats. Methods: Rats were divided into five groups ( n = 8): control, THQ, olive oil, DOX (a single dose of 15 mg/kg intraperitoneally (i.p.) on seventh day of the experiment), and DOX + THQ (10 mg/kg THQ per day and 15 mg/kg DOX i.p. on seventh day). Animals were euthanized, and testis tissues were evaluated histopathologically. Caspase 3 and HSP90 immunostaining were performed to determine the expression levels of these proteins among groups. Terminal deoxynucleotidyl transferase 2′-deoxyuridine, 5′-triphosphate nick-end labeling method was used for evaluation of apoptotic index. Moreover, serum testosterone levels and total antioxidant status (TAS) and total oxidant status (TOS) in testicular tissue were measured by ELISA assay. Results: The DOX group had histopathological deterioration compared to the control group. There was an increase in apoptotic index, caspase 3 and HSP90 expressions in the DOX group. While TAS level of the DOX group decreased, TOS level increased when compared with the other groups. Serum testosterone levels in the DOX group decreased compared to the control group. However, there was improvement in testicular tissue in DOX + THQ group compared to the DOX group. There was a decrease in apoptotic index, caspase 3, and HSP90 expressions in DOX + THQ group compared to the DOX group. Testosterone level of DOX + THQ significantly increased compared to the DOX group. Conclusion: We suggest that THQ can be used as a protective agent to reduce the toxic effects of DOX.

Antioxidant and cytoprotective effects of Nigella sativa L. seeds on the testis of monosodium glutamate challenged rats

“…In agreement with a previous study 81 , concurrent administration of NSS to MSG intoxicated rats provided cytoprotection against the development of MSG-induced apoptosis which can be explained based on its antioxidant and anti-inflammatory properties 108 . Thymoquinone exhibits anti-apoptotic properties evident by down-regulation in immuno-expression of caspase 3 and heat shock proteins in the testis of doxorubicin challenged rats 109 . Stabilization of the cell membrane due to its hydrophobicity 110 and inhibition of ataxia telangiectasia mutated kinase-dependent signaling pathway 111 are possible mechanistic pathways by which squalene blocks the action of pro-apoptotic inducers.…”

Alpha‐lipoic acid may ameliorate testicular damage by targeting dox‐induced altered antioxidant parameters, mitofusin‐2 and apoptotic gene expression

“…In the DOX and DOX + ALA groups, a single intraperitoneal (i.p.) dose of 15 mg/kg DOX was administered (Öztürk et al., 2020). In the DOX + ALA and ALA groups, 50 mg/kg ALA dissolved in saline was administered every other day by oral gavage for 28 days (El‐Sayed et al., 2017).…”

“…DOX has negative effects on the male reproductive system, and thus, it may cause male infertility (Türedi et al., 2015). Although no definite mechanism has been clarified, recent studies have pointed to the potential role of oxidative stress, cellular apoptosis, lipid peroxidation, generation of excessive reactive oxygen species (ROS) and mitochondrial disruption in the DOX‐induced testicular toxicity (Öztürk et al., 2020; Yeh et al., 2009).…”

Effects of Vitamin D on doxorubucin-induced lung injury and TRPM2 immunoreactivity in rats

“…The total redox statuses of individuals were best evaluated with TAS and TOS levels combined [31,32]. DOX treatment has been reported to lead to an increase in TOS level and a decrease in TAS level in testis [33], and heart [34], and tissues. These findings show that DOX disrupted the oxidant-antioxidant balance and led to tissue damage.…”