Rosmarinic Acid Alleviated Cyclophosphamide-Induced Gonadal Toxicity in Adult Male Rats

Year 2025, Volume: 8 Issue: 1, 73 - 80

Firat Sahin , Engin Deveci , Fırat Aşır , Merve Gulsen Bal Albayrak , Ebru Gökalp Özkorkmaz

Abstract

Abstract
Background/Aim: This study aimed to investigate the potential protective effects of rosmarinic acid (RA) against cyclophosphamide (CP)-induced gonadal toxicity in male Wistar Albino rats. Specifically, the research focused on the modulation of apoptotic pathways, with an emphasis on Bax protein expression, and utilized bioinformatic analyses to elucidate the key molecular mechanisms and signaling pathways underlying the observed effects.
Materials and Methods: The experimental design consisted of four groups: Control (administered saline), RA (administered rosmarinic acid), CP (administered cyclophosphamide), and RA+CP (administered a combination of rosmarinic acid and cyclophosphamide). Following a 14-day treatment period, body weight, serum malondialdehyde (MDA) levels, and Bax protein expression in testicular tissue were evaluated. Additionally, a protein-protein interaction (PPI) network influenced by RA and CP was constructed using STITCH and subsequently analyzed in Cytoscape. Functional enrichment analysis was performed to identify key molecular pathways associated with Bax regulation, with an emphasis on clusters exhibiting significant associations (p <0.05) for enhanced interpretability.
Results: In the CP group, a significant reduction in body weight was observed, alongside elevated serum malondialdehyde (MDA) levels, indicative of heightened oxidative stress, and increased Bax protein expression, reflecting enhanced apoptotic activity. In contrast, the RA+CP group exhibited preservation of body weight, reduced Bax expression, and lowered MDA levels, closely resembling the profiles of the control group. Bioinformatic analyses revealed that CP predominantly activated molecular pathways associated with oxidative stress, apoptosis, and lipid metabolism. In comparison, RA treatment modulated pathways involved in mitochondrial protection, endoplasmic reticulum (ER) stress response, and the regulation of cytochrome c release, highlighting its potential protective role.
Conclusion: This study demonstrates that the antioxidant and anti-inflammatory properties of rosmarinic acid (RA) significantly mitigate cyclophosphamide (CP)-induced gonadal toxicity in male rats. The protective effects of RA are evident in its ability to preserve body weight, reduce oxidative stress, and suppress Bax protein expression, a key marker of apoptosis. Furthermore, in-silico analyses confirm that RA exerts its protective effects by modulating critical apoptotic pathways, specifically through the inhibition of Bax expression and the reduction of oxidative stress. These findings underscore the potential of RA as a therapeutic agent to prevent CP-induced gonadal damage, offering promise for its future application in protecting against chemotherapy-related reproductive toxicity.

Keywords

bax expression, cyclophoshamide, rosmarinic acid, gonadal toxicity

Ethical Statement

Çalışmamım tüm etik kurul beyanları sunulmuştur.

Supporting Institution

DİCLE ÜNİVERSİTESİ

Project Number

TIP.21.003

Thanks

Tarafıma ait “[Rosmarinic Acid Alleviated Cyclophosphamide-Induced Gonadal Toxicity in Adult Male Rats ]” başlıklı çalışmamın derginizde yayınlanması sürecinde gösterdiğiniz ilgi, titizlik ve değerli katkılarınız için teşekkürlerimi sunmak isterim. Editörlük süreci boyunca sağladığınız hızlı ve profesyonel geri dönüşler, çalışmamızın kalitesini artırmamıza önemli ölçüde yardımcı olmuştur. Ayrıca, alanımıza yaptığınız katkılar ve bilimsel yayıncılığı destekleme konusundaki özveriniz için minnettar olduğumu belirtmek isterim. Çalışmamızın yayınlanması, benim ve ekibim için büyük bir gurur kaynağıdır. Derginizin bilimsel camiadaki önemli rolü ve prestijine yakışır bir yayın sunabilmiş olmayı ümit ediyoruz. Gelecekte de sizinle çalışmayı ve yeni katkılar sunmayı sabırsızlıkla bekliyorum. Saygılarımla,

Rosmarinik Asit, Erişkin Erkek Sıçanlarda Siklofosfamid Kaynaklı Gonadal Toksisiteyi Hafifletti

Abstract

Abstract
Background/Aim: This study aimed to investigate the potential protective effects of rosmarinic acid (RA) against cyclophosphamide (CP)-induced gonadal toxicity in male Wistar Albino rats. Specifically, the research focused on the modulation of apoptotic pathways, with an emphasis on Bax protein expression, and utilized bioinformatic analyses to elucidate the key molecular mechanisms and signaling pathways underlying the observed effects.
Materials and Methods: The experimental design consisted of four groups: Control (administered saline), RA (administered rosmarinic acid), CP (administered cyclophosphamide), and RA+CP (administered a combination of rosmarinic acid and cyclophosphamide). Following a 14-day treatment period, body weight, serum malondialdehyde (MDA) levels, and Bax protein expression in testicular tissue were evaluated. Additionally, a protein-protein interaction (PPI) network influenced by RA and CP was constructed using STITCH and subsequently analyzed in Cytoscape. Functional enrichment analysis was performed to identify key molecular pathways associated with Bax regulation, with an emphasis on clusters exhibiting significant associations (p <0.05) for enhanced interpretability.
Results: In the CP group, a significant reduction in body weight was observed, alongside elevated serum malondialdehyde (MDA) levels, indicative of heightened oxidative stress, and increased Bax protein expression, reflecting enhanced apoptotic activity. In contrast, the RA+CP group exhibited preservation of body weight, reduced Bax expression, and lowered MDA levels, closely resembling the profiles of the control group. Bioinformatic analyses revealed that CP predominantly activated molecular pathways associated with oxidative stress, apoptosis, and lipid metabolism. In comparison, RA treatment modulated pathways involved in mitochondrial protection, endoplasmic reticulum (ER) stress response, and the regulation of cytochrome c release, highlighting its potential protective role.
Conclusion: This study demonstrates that the antioxidant and anti-inflammatory properties of rosmarinic acid (RA) significantly mitigate cyclophosphamide (CP)-induced gonadal toxicity in male rats. The protective effects of RA are evident in its ability to preserve body weight, reduce oxidative stress, and suppress Bax protein expression, a key marker of apoptosis. Furthermore, in-silico analyses confirm that RA exerts its protective effects by modulating critical apoptotic pathways, specifically through the inhibition of Bax expression and the reduction of oxidative stress. These findings underscore the potential of RA as a therapeutic agent to prevent CP-induced gonadal damage, offering promise for its future application in protecting against chemotherapy-related reproductive toxicity.

Keywords

bax ekspersyonu, siklofosfamid, rosmarinik asit, gonadal toksisite

Project Number

TIP.21.003

References

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