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Propolis mitigates busulfan-induced testicular dysfunction in rats: insights into redox stabilization, PCNA
Elham A AbdAllah1, Basant A Eid1, Hassan A Hussein2,3
1Zoology Department, Faculty of Science, New Valley University, New Valley, Egypt.
Introduction:
Testicular cytofunctional defects are among the most hazardous effects of cancer chemotherapies. Propolis mitigates the fertility problems associated with gonadotoxic agents through its redox stabilizing, anti-apoptotic, and cytoprotective properties due to presence of bioactive agents identified in our study by gas chromatography-mass spectrometry analysis including, flavonoids, terpenes, aliphatic and aromatic compounds, and amino acids. Herein, we investigated the potential reversal effects of aqueous propolis on busulfan-induced reproductive abnormalities in adult rats.
Methods:
Thirty rats were randomly assigned to five experimental groups, with six animals per group, for duration of 6 weeks. The control group received only the vehicle daily through oral gavage. The DMSO group was given a single intraperitoneal injection of DMSO. The busulfan group received a single intraperitoneal injection of busulfan at a dose of 20 mg/kg body weight, followed by daily oral gavage. The propolis group was administered propolis daily via oral gavage at a dose of 100 mg/kg body weight. In the busulfan + propolis group, rats received a single intraperitoneal injection of busulfan at 20 mg/kg body weight, combined with daily oral gavage of propolis at a dose of 100 mg/kg body weight.
Results And Discussion:
Busulfan exposure led to a decrease in serum levels of follicle-stimulating hormone, testosterone, and estradiol 17β, along with an increase in luteinizing hormone. It negatively affected sperm outcomes, causing a decline in sperm count and the percentages of live, normal, and motile sperm, while increasing the percentages of dead and abnormal sperm. Furthermore, busulfan disrupted the testicular defense system, as indicated by elevated testicular malondialdehyde levels and reductions in testicular nitric oxide and reduced glutathione levels, catalase and superoxide dismutase activities, as well as serum total antioxidant capacity. Marked histopathological changes were observed, in concomitant with strong immunoreactivity for proliferating cell nuclear antigen and caspase-3 in germ cells. Propolis supplementation effectively mitigated all these abnormalities in busulfan-intoxicated rats. Propolis is suggested as a potential complementary adjuvant for managing busulfan-induced reproductive dysfunction, owing to its reproductive hormone-modulating, redox-stabilizing, sperm-protective, and anti-apoptotic properties.
Insights
Propolis supplementation reversed reproductive abnormalities caused by busulfan chemotherapy in rats. This natural compound demonstrated protective effects on testicular function, hormone levels, sperm quality, and antioxidant status, suggesting its potential as a complementary therapy.
Area of Science:
- Reproductive Biology
- Toxicology
- Pharmacology
Background:
- Cancer chemotherapies, such as busulfan, can cause significant testicular damage and fertility issues.
- Propolis, a natural resinous substance, possesses bioactive compounds with antioxidant, anti-apoptotic, and cytoprotective properties.
- Understanding propolis's potential to mitigate chemotherapy-induced reproductive toxicity is crucial for patient care.
Purpose of the Study:
- To investigate the protective effects of aqueous propolis on busulfan-induced reproductive abnormalities in adult male rats.
- To evaluate propolis's impact on reproductive hormones, sperm parameters, testicular oxidative stress markers, and testicular histology.
Main Methods:
- Adult rats were divided into five groups: control, vehicle, busulfan, propolis, and busulfan + propolis.
- Busulfan was administered intraperitoneally, while propolis was given daily via oral gavage for six weeks.
- Hormone levels, sperm characteristics, oxidative stress markers (malondialdehyde, nitric oxide, glutathione), antioxidant enzyme activities, and testicular histopathology were assessed.
Main Results:
- Busulfan treatment significantly altered reproductive hormone levels (FSH, LH, testosterone, estradiol), reduced sperm count and quality, and induced oxidative stress in testicular tissue.
- Histopathological examination revealed damage to germ cells, with increased markers of cell proliferation and apoptosis (PCNA, caspase-3).
- Propolis supplementation effectively counteracted busulfan-induced testicular toxicity, restoring hormone balance, improving sperm parameters, alleviating oxidative stress, and reducing histopathological damage.
Conclusions:
- Aqueous propolis demonstrates significant potential in reversing busulfan-induced reproductive dysfunction in male rats.
- Propolis exhibits reproductive hormone-modulating, redox-stabilizing, sperm-protective, and anti-apoptotic properties.
- Propolis can be considered a promising complementary adjuvant therapy for managing chemotherapy-induced reproductive toxicity.
