A new thiocyanoacetamide (2-cyano-2-p-nitrophenyl-N-benzylthioamide) reduces doxorubicin-induced in vitro toxicity in Sertoli cells by decreasing apoptosis and autophagy

Boussada, Marwa; Dias, Tânia R.; Crisóstomo, Luís; Akacha, Azaiez Ben; Ali, Ridha Ben; May, Michèle Véronique El; Alves, Marco G.; Oliveira, Pedro F.

doi:10.1016/j.theriogenology.2019.08.030

Cited by 7 publications

(4 citation statements)

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“…5,6 A common way to decrease the side effects of Dox is the utilization of adjuvant compounds, which reduce the therapeutic dosage and keeps or increases the therapeutic outcome. 7 Different adjuvants are used in combination with Dox including cyclophosphamide, 8,9 5-uorouracil, 7,10 b-caryophyllene, 11 thiocyanoacetamide, 12 ifosfamide, 13 furanodiene, 14 quercetin, 15 quinacrine, 16 orange peel extract, naringin 17 and conferone. 18 Conferone is a natural and non-toxic compound, which is extracted from the fruits and roots of the self-growing Ferula species, which has signicant anticancer properties, such as antiangiogenic effects, suppressing P-glycoprotein (P-gp)mediated drug efflux, and increasing the cellular uptake and accumulation of Dox in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Novel pH-sensitive and biodegradable micelles for the combined delivery of doxorubicin and conferone to induce apoptosis in MDA-MB-231 breast cancer cell line

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Novel pH-sensitive and biodegradable micelles for the combined delivery of doxorubicin and conferone to induce apoptosis in MDA-MB-231 breast cancer cell line

et al. 2020

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“…Here we have built upon our previous studies to show that TA can alleviate DOX‐induced testicular toxicity, and provide key information regarding its protective potential. The underlying reason behind TA association with DOX in an attempt to reduce its gonadotoxicity was based on TA antioxidant potential (Ali et al, 2017), and its ability to diminish DOX‐triggered damages in vivo (Boussada et al, 2017), in vitro (Boussada, Ali, et al, 2019; Boussada, Dias, et al, 2019), and ex vivo (Boussada, Ali, et al, 2019; Boussada, Dias, et al, 2019). Hence, this study aims to provide continuity to our prior work and confirm the protective effect of the newly synthesized TA, against the structural impairment inflcited by DOX in the germinal epithelium.…”

Section: Discussionmentioning

confidence: 99%

“…Mounting medium (#ab64230) was provided by Abcam (USA). The chemical synthesis of the 2‐cyano‐2‐ p ‐nitrophenyl‐ N ‐benzylthioamide or TA was performed as previously described by Boussada, Ali, et al (2019); Boussada, Dias, et al (2019).…”

Section: Methodsmentioning

confidence: 99%

“…In the context of alternative therapy implementation, a new derivative of thioamide; TA, was developed by our group and tested against the detrimental effects of DOX in vivo (Boussada et al, 2017), in vitro in Sertoli cell culture (Boussada, Ali, et al, 2019; Boussada, Dias, et al, 2019) and ex vivo in freshly extracted sperm cells (Boussada, Ali, et al, 2019; Boussada, Dias, et al, 2019). Data obtained from the studies mentioned above, brought to light interesting results, in terms of improvement of spermatogenesis, decrease of SC death triggered by the DOX, and enhancement of sperm cell oxygen consumption and survival, by the co‐therapy of DOX and TA.…”

Section: Introductionmentioning

confidence: 99%

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In vivo exposure to a new 2‐cyano‐2‐ p ‐nitrophenyl‐ N ‐benzylthioamide decreases doxorubicin‐triggered structural damages in the mature testis

et al. 2022

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The use of doxorubicin (DOX) in clinical practice continues to be challenged by its severe toxicity. DOX cytotoxic activity is not only directed against malignant tumours, given that the treatment will damage healthy tissues as well leading to irreversible injuries. This study aimed to address the in vivo effects of DOX and its co‐administration with a new analog of thioamide; thiocyanoacetamide (TA) on the germinal epithelium. Thus, male rats received either intravenous injection (iv) of 0.03 mg/kg of body weight/week, 0.9% NaCl and were regarded as the control group (CTR), treated with DOX (3.7 mg/kg/week iv), TA [10 mg/kg/day intragastrically (ig)] or a co‐supplementation of DOX and TA. After 50 days, the left testes were dissected and used for toluidine blue, periodic acid‐Schiff (PAS) staining (to evaluate the change in polysaccharides/glycoproteins content), and transmission electron microscopy (TEM) (to assess the morphological damages). To estimate the impact of the test compounds on mitochondrial biogenesis, the expression of NAD‐dependent deacetylase sirtuin‐3 (SIRT‐3) and proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α) were evaluated by immunofluorescence. Apoptotic cells were observed using Hoechst 33324 fluorescent staining. Data showed testicular injuries in the DOX‐treated group, manifested by a significant decrease in total germ cell (GC) number, alteration of Sertoli cell (SC) nucleolus, anchoring junction, along with modifications of the basement membrane (BM) regularity and increase in apoptotic cell count. Mitochondrial aspect and SIRT‐3 and PGC‐1α expression in the testis were unaffected by the DOX. Co‐therapy increased GC number, decreased apoptotic cell count, and restored the BM and anchoring junction regular aspects. This study provides novel insights into understanding DOX‐mediated impairment in rats' testis and might offer some basis for the emerging new alternative therapeutic schemes in male patients undergoing chemotherapy.

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Modulatory effect of liraglutide on doxorubicin-induced testicular toxicity and behavioral abnormalities in rats: role of testicular-brain axis

Alafifi

Wahdan

Elhemiely

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Doxorubicin (DOX) is a powerful chemotherapeutic agent used in many types of malignancies. However, its use results in testicular damage. DOX-induced testicular damage results in low level of serum testosterone which may affect cognitive function. The current study investigated the protective effect of liraglutide (50, 100 μg/kg/day) in testicular toxicity and the consequent cognitive impairment induced by DOX. DOX treatment reduced sperm count (62%) and sperm motility (53%) and increased sperm abnormalities (786%), as compared to control group. DOX also reduced serum testosterone level (85%) and the gene expression of testicular 3β-HSD (68%) and 17β-HSD (82%). Moreover, it increased testicular oxidative stress (MDA and GSH) by 103% and 59%, respectively, apoptotic (caspase-3 and P53) by 996% and 480%, respectively. In addition, DOX resulted in increasing autophagic markers including PAKT, mTOR, and LC3 by 48%, 56%, and 640%, respectively. Additionally, rats’ behavior in Y-maze (60%) and passive avoidance task (85%) was disrupted. The histopathological results of testis and brain supported the biochemical findings. Treatment with liraglutide (100 μg/kg/day) significantly abrogated DOX-induced testicular damage by restoring testicular architecture, increasing sperm count (136%) and sperm motility (106%), and decreasing sperm abnormalities (84%) as compared to DOX group. Furthermore, liraglutide increased serum testosterone (500%) and steroidogenesis enzymes 3β-HSD (105%) and 17β-HSD (181%) along with suppressing oxidative stress (MDA and GSH) by 23% and 85%, respectively; apoptotic (caspase-3 and P53) by 59% and55%, respectively; and autophagic markers including PAKT, mTOR, and LC3 by 48%, 97%, and 60%, respectively. Moreover, it enhanced the memory functions in passive avoidance and Y-maze tests (132%). In conclusion, liraglutide is a putative agent for protection against DOX-induced testicular toxicity and cognitive impairment through its antioxidant, antiapoptotic, and antiautophagic effects.

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A new thiocyanoacetamide (2-cyano-2-p-nitrophenyl-N-benzylthioamide) reduces doxorubicin-induced in vitro toxicity in Sertoli cells by decreasing apoptosis and autophagy

Cited by 7 publications

References 80 publications

Novel pH-sensitive and biodegradable micelles for the combined delivery of doxorubicin and conferone to induce apoptosis in MDA-MB-231 breast cancer cell line

Novel pH-sensitive and biodegradable micelles for the combined delivery of doxorubicin and conferone to induce apoptosis in MDA-MB-231 breast cancer cell line

In vivo exposure to a new 2‐cyano‐2‐ p ‐nitrophenyl‐ N ‐benzylthioamide decreases doxorubicin‐triggered structural damages in the mature testis

Modulatory effect of liraglutide on doxorubicin-induced testicular toxicity and behavioral abnormalities in rats: role of testicular-brain axis

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