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Apigetrin ameliorates doxorubicin prompted testicular damage: biochemical, spermatological and histological based
Muhammad Umar Ijaz1, Saba Yaqoob2, Ali Hamza2
1Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad, 38040, Pakistan. umar.ijaz@uaf.edu.pk.
Abstract:
Doxorubicin (DOX) is a highly effective, commonly prescribed, potent anti-neoplastic drug that damages the testicular tissues and leads to infertility. Apigetrin (APG) is an important flavonoid that shows diverse biological activities. The present research was designed to evaluate the alleviative role of APG against DOX-induced testicular damages in rats. Forty-eight adult male albino rats were randomly distributed into 4 groups, control, DOX administered (3 mgkg-1), DOX + APG co-administered (3 mgkg-1 of DOX; 15 mgkg-1 of APG), and APG administered group (15 mgkg-1). Results of the current study indicated that DOX treatment significantly reduced the activities of superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT) and glutathione peroxidase (GPx), while increasing the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). DOX treatment also reduced the sperm count, viability, and motility. Moreover, DOX significantly increased the sperm morphological anomalies and reduced the levels of plasma testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The administration of DOX significantly increased the expressions of Bax and Caspase-3, as well as the levels of inflammatory markers. Additionally, DOX treatment significantly downregulated the expressions of steroidogenic enzymes (StAR, 3β-HSD and 17β-HSD) and Bcl-2. Furthermore, DOX administration provoked significant histopathological abnormalities in the testicular tissues. However, APG supplementation significantly reversed all the testicular damages due to its androgenic, anti-apoptotic, anti-oxidant and anti-inflammatory nature. Therefore, it is concluded that APG may prove a promising therapeutic agent to treat DOX-induced testicular damages.
Insights
Apigetrin (APG) may protect against Doxorubicin (DOX)-induced testicular damage. APG reversed DOX
Area of Science:
- Reproductive Toxicology
- Pharmacology
- Biochemistry
Background:
- Doxorubicin (DOX), a potent anti-neoplastic drug, can cause significant testicular damage and infertility.
- Flavonoids, such as Apigetrin (APG), possess diverse biological activities with potential therapeutic applications.
- Understanding the protective mechanisms of APG against chemotherapy-induced reproductive toxicity is crucial.
Purpose of the Study:
- To evaluate the protective effects of Apigetrin (APG) against Doxorubicin (DOX)-induced testicular toxicity in a rat model.
- To investigate the impact of APG on oxidative stress, sperm parameters, hormone levels, and testicular histopathology following DOX administration.
Main Methods:
- Adult male albino rats were divided into four groups: control, DOX-treated, DOX + APG co-treated, and APG-treated.
- Biochemical assays were performed to measure antioxidant enzyme activities (SOD, GSR, CAT, GPx) and lipid peroxidation (MDA, ROS).
- Sperm count, viability, motility, morphology, hormone levels (testosterone, LH, FSH), gene expression (Bax, Caspase-3, Bcl-2, StAR, 3β-HSD, 17β-HSD), and testicular histopathology were assessed.
Main Results:
- DOX treatment significantly decreased antioxidant enzyme activities and sperm quality while increasing oxidative stress markers, sperm anomalies, and inflammatory markers.
- DOX administration led to reduced levels of testosterone, LH, and FSH, alongside altered expression of apoptotic and steroidogenic genes.
- APG supplementation significantly ameliorated DOX-induced testicular damage, restoring biochemical parameters, improving sperm quality, normalizing hormone levels, and mitigating histopathological changes.
Conclusions:
- Apigetrin (APG) demonstrates significant protective effects against Doxorubicin (DOX)-induced testicular damage in rats.
- APG's protective mechanisms involve its antioxidant, anti-apoptotic, anti-inflammatory, and androgenic properties.
- APG shows promise as a therapeutic agent for mitigating chemotherapy-induced male reproductive toxicity.
