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Published on: May 16, 2020
Protective effects of diosmin on doxorubicin-induced testicular toxicity in rat
Alireza Malayeri1, Shahin Moradi Birgani1, Zahra Basir2
1Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Abstract:
Doxorubicin (DOX) can be applied to treat several cancers. DOX-induced oxidative stress causes testicular damage. Diosmin (DIO), as a potent antioxidant, reduces many drugs' side effects. We determined DIO therapeutic effects on DOX-related testicular toxicity. Forty rats were assigned to five groups as control, DOX (2.5 mg/kg six i.p. injections at equal intervals over two weeks), DOX + DIO (25, 50, 100 mg/kg, orally, daily, for two weeks) groups. Oxidative and antioxidant markers, fertility parameters levels, sperm parameters, and a histopathological examination were analyzed. DOX group showed a significant decrease in the number of spermatogonia, primary spermatocytes, and sertoli cells, seminiferous tubular diameter, seminiferous luminal diameter, and seminiferous epithelial height. Moreover, testosterone levels, glutathione (GSH) levels, catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities showed a significant decrease. Furthermore, nitric oxide (NO) and malondialdehyde (MDA) contents and also follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels showed a significant increase in the DOX group compared to the control group. DIO improved DOX-related alterations in levels of hormones, spermatogonia, spermatocytes, and sertoli cell number, and seminiferous diameters (tubular, luminal, and epithelial height). Furthermore, GSH level, SOD, GPx, and CAT activities showed a significant increase, and MDA and NO contents showed a significant decrease in the DOX + DIO group than the DOX group. The results indicate that DIO mitigate DOX-induced testicular toxicity by its anti-oxidant activity.
Insights
Diosmin (DIO) effectively mitigates testicular toxicity induced by the chemotherapy drug Doxorubicin (DOX). DIO
Area of Science:
- Reproductive Toxicology
- Pharmacology
- Biochemistry
Background:
- Doxorubicin (DOX) is a widely used chemotherapy agent.
- DOX treatment can lead to significant testicular damage due to induced oxidative stress.
- Diosmin (DIO), a natural flavonoid, possesses potent antioxidant properties.
Purpose of the Study:
- To investigate the protective effects of Diosmin (DIO) against Doxorubicin (DOX)-induced testicular toxicity in a rat model.
- To evaluate DIO's impact on oxidative stress markers, hormonal balance, sperm parameters, and testicular histology following DOX administration.
Main Methods:
- Forty rats were divided into five groups: control, DOX, and DOX treated with three different doses of DIO.
- DOX was administered via intraperitoneal injection, while DIO was given orally daily for two weeks.
- Analysis included oxidative/antioxidant markers, hormone levels (testosterone, FSH, LH), sperm parameters, and histopathological examination of testicular tissues.
Main Results:
- DOX treatment significantly reduced sperm count, germ cell populations (spermatogonia, spermatocytes, Sertoli cells), and seminiferous tubule dimensions.
- DOX administration decreased levels of antioxidant enzymes (GSH, CAT, GPx, SOD) and testosterone, while increasing oxidative stress markers (NO, MDA) and gonadotropins (FSH, LH).
- DIO treatment dose-dependently reversed these DOX-induced negative effects, improving testicular histology, hormone levels, and antioxidant status.
Conclusions:
- Diosmin (DIO) demonstrates significant protective effects against Doxorubicin (DOX)-induced testicular toxicity.
- DIO's therapeutic benefits are attributed to its potent antioxidant activity, which counteracts DOX-induced oxidative stress.
- DIO represents a promising therapeutic agent for mitigating chemotherapy-related reproductive side effects.
