“The Potential Protective Effect of Ferulic Acid against Gamma Radiation-Induced Testicular Damage”
Rania Abdel Monaim Ahmed Gawish;
Abstract
Nowadays, excessive attention has been given to the radiotherapy as a cause of male infertility.Meanwhile, none of the currently available methods for testicular protection and fertility preservation is ideal and guarantees future fertility. The need for more effective strategy to protect the testis from the cytotoxic radiotherapy is highly intensified. Thus, the present study was aimed to evaluate the radioprotective or curative effects of FA against γ-irradiation induced testicular damage in vivo together with studying its effect on different OS biomarkers, SIRT1 expression and activity, PARP1 expression and level, sperm head abnormality and cytosolic calcium content as well as to explore the role of SIRT1 and PARP1 in male fertility. In order to fulfil our aim, this study was conducted on 50 male rats divided into the following five groups:
Group 1: Control group orallyadministered with DW (0.5ml/100g B.W.)once daily for 7days.
Group 2: Irradiated group (single dose of 5Gy, whole body γ-irradiation).
Group 3: Rats were orallyadministered FA (50 mg/kg B.W.) once daily for 7days.
Group 4: Protective group orallyadministered FA (50mg/kg B.W.) oncefor 7 days then exposed towhole body γ-rays (5Gy).
Group 5: Curative group were exposed towhole body γ-rays (5Gy) then were treated with FA (50mg/kg B.W.) once daily for 7days.
The following parameters were investigated:
1- Testes/body weightrelative ratio
2- The frequency of the sperm head abnormalities
3- Oxidative stress biomarkers; CAT and SOD activities, GSH and MDA contents as well as FRAP assay
4- Cytosolic calcium content
5- Expression and levelof PARP1
6- Sirtuin1 activity and expression
7- Testosterone hormone level
8-Histopathological examination:hematoxylin and eosin were used for routine histological examination
9- Trace elements contents: Mn, Zn, Fe and Cu contents were determinedin testicular tissue
The findings of the present study can be summarized as follows:
1- Seven days after irradiation; the animals exhibited a decrease in their testes/body weightrelative ratio. However, treatment with FA pre or post γ-irradiation nearly normalized this significant decrease as compared to control animals.
2- Male adult rats exposed to γ-rays exhibited significant increase in sperm head abnormalities. Although, FA administration pre or post irradiation ameliorated the values of the sperm abnormalities, mutation factor and mutation index in comparison to control group.
3- Gamma-irradiation induced a significant increase in MDA content and a significant decrease in the values of GSH, SOD and CAT. While, treatment with FA pre or post exposure to γ-radiation afforded significant protection against radiation-induced OS and modulated thevalues of MDA, GSH, SOD and CAT in testicular tissues toward the control values.
4- The total antioxidant power was measured by the FRAP assay in tissue homogenate, γ-irradiation induced a significant reduction in FRAP assay. Conversely, FA treatment pre or postγ-irradiation nearly normalizes the value of FRAP assay.
5- Exposure to γ-radiation caused a marked increase in testicular cytosolic calcium content. In contrast, treatment of irradiated rats with FA pre or post irradiation significantly decreased this elevation as compared to control group.
6- Interestingly, γ-irradiation caused a significantup-regulation of testicular PARP1 expression and level as well asmassive depletion of testicular SIRT1 expression and activity.While, treatment with FA pre or post exposure to γ-rays minimized PARP1 over activation and expression, and nearly normalized the values of SIRT1 expression and activity.
7- In γ-irradiation treated group, the serum testosterone level displayed a significant decrease.On the other hand, treatment of male rats with FA pre or post irradiation ameliorated this decrease as compared to control.
8- Microscopical examination using hematoxylin and eosin, examination of testicular tissues of irradiated rats showed congestion,edemaand incomplete cessation of spermato-genesis that characterized by disorganization of the spermato-gonia with degeneration and necrosis of most of them. Conversely, treatment of rats with FA preserved testicular tissues from radiation-induced hemorrhage and degeneration.
9- Gamma-irradiation caused significant alteration in the values of testicular trace elements (Zn, Cu, Fe andMn) contents. However, treatment of the irradiated rats with FA pre or post irradiation nearly modulates the values of testicular trace elements to normal values.
Together, these findings support the conclusion that FA provides evidence for testicular radio-protective or curative roles. The mechanism underlying these promising effects could be through enhancing SIRT1activity by increasing its expression, while decreasing PARP1 level, reaching a value that can repair γ-irradiation induced DNA damage, either by decreasing its gene expression or through decreasing cytosolic calcium contents and augmented total antioxidant power, as a result minimizing lipid peroxidation and preserving testicular histology, enhancing testosterone secretion, decreasing sperm head abnormalities and subsequently male fertility preservation.
Group 1: Control group orallyadministered with DW (0.5ml/100g B.W.)once daily for 7days.
Group 2: Irradiated group (single dose of 5Gy, whole body γ-irradiation).
Group 3: Rats were orallyadministered FA (50 mg/kg B.W.) once daily for 7days.
Group 4: Protective group orallyadministered FA (50mg/kg B.W.) oncefor 7 days then exposed towhole body γ-rays (5Gy).
Group 5: Curative group were exposed towhole body γ-rays (5Gy) then were treated with FA (50mg/kg B.W.) once daily for 7days.
The following parameters were investigated:
1- Testes/body weightrelative ratio
2- The frequency of the sperm head abnormalities
3- Oxidative stress biomarkers; CAT and SOD activities, GSH and MDA contents as well as FRAP assay
4- Cytosolic calcium content
5- Expression and levelof PARP1
6- Sirtuin1 activity and expression
7- Testosterone hormone level
8-Histopathological examination:hematoxylin and eosin were used for routine histological examination
9- Trace elements contents: Mn, Zn, Fe and Cu contents were determinedin testicular tissue
The findings of the present study can be summarized as follows:
1- Seven days after irradiation; the animals exhibited a decrease in their testes/body weightrelative ratio. However, treatment with FA pre or post γ-irradiation nearly normalized this significant decrease as compared to control animals.
2- Male adult rats exposed to γ-rays exhibited significant increase in sperm head abnormalities. Although, FA administration pre or post irradiation ameliorated the values of the sperm abnormalities, mutation factor and mutation index in comparison to control group.
3- Gamma-irradiation induced a significant increase in MDA content and a significant decrease in the values of GSH, SOD and CAT. While, treatment with FA pre or post exposure to γ-radiation afforded significant protection against radiation-induced OS and modulated thevalues of MDA, GSH, SOD and CAT in testicular tissues toward the control values.
4- The total antioxidant power was measured by the FRAP assay in tissue homogenate, γ-irradiation induced a significant reduction in FRAP assay. Conversely, FA treatment pre or postγ-irradiation nearly normalizes the value of FRAP assay.
5- Exposure to γ-radiation caused a marked increase in testicular cytosolic calcium content. In contrast, treatment of irradiated rats with FA pre or post irradiation significantly decreased this elevation as compared to control group.
6- Interestingly, γ-irradiation caused a significantup-regulation of testicular PARP1 expression and level as well asmassive depletion of testicular SIRT1 expression and activity.While, treatment with FA pre or post exposure to γ-rays minimized PARP1 over activation and expression, and nearly normalized the values of SIRT1 expression and activity.
7- In γ-irradiation treated group, the serum testosterone level displayed a significant decrease.On the other hand, treatment of male rats with FA pre or post irradiation ameliorated this decrease as compared to control.
8- Microscopical examination using hematoxylin and eosin, examination of testicular tissues of irradiated rats showed congestion,edemaand incomplete cessation of spermato-genesis that characterized by disorganization of the spermato-gonia with degeneration and necrosis of most of them. Conversely, treatment of rats with FA preserved testicular tissues from radiation-induced hemorrhage and degeneration.
9- Gamma-irradiation caused significant alteration in the values of testicular trace elements (Zn, Cu, Fe andMn) contents. However, treatment of the irradiated rats with FA pre or post irradiation nearly modulates the values of testicular trace elements to normal values.
Together, these findings support the conclusion that FA provides evidence for testicular radio-protective or curative roles. The mechanism underlying these promising effects could be through enhancing SIRT1activity by increasing its expression, while decreasing PARP1 level, reaching a value that can repair γ-irradiation induced DNA damage, either by decreasing its gene expression or through decreasing cytosolic calcium contents and augmented total antioxidant power, as a result minimizing lipid peroxidation and preserving testicular histology, enhancing testosterone secretion, decreasing sperm head abnormalities and subsequently male fertility preservation.
Other data
| Title | “The Potential Protective Effect of Ferulic Acid against Gamma Radiation-Induced Testicular Damage” | Other Titles | "التأثيرالوقائي المحتمل لحمض الفريولك ضد الإشعاع الجامي المسبب لتلف الخصية" | Authors | Rania Abdel Monaim Ahmed Gawish | Issue Date | 2017 |
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