الفهرس 
Hormonal control of testicular function.Only 14 pages are availabe for public view
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Abstract
6- SUMMARY AND CONCLUSIONS
Summary
The aim of the current study was to test the modulatory effect of liraglutide against DOX-induced testicular toxicity and the subsequent cognitive impairment in rats and to investigate the possible underlying mechanisms for the potential protection.
Experimental design:
Study was divided into two parts:
Part-A; Screening the protective dose of liraglutide against DOX-induced testicular toxicity: a preliminary dose finding study was conducted using 72 rats to select the optimal dose of liraglutide for the treatment of testicular toxicity induced by DOX in rats. The animals were divided into 6 groups (n=12) as follows
• group 1: CONTROL; received the vehicles (normal saline)
• group 2: DOX; received a total cumulative dose of DOX (18 mg/kg, i.p.) dissolved in normal saline, in six equally divided doses, on the 8th, 10th, 12th, 15th, 17th and 19th day from the start of the experiments(Kabel, 2018).
• group 3: DOX + LIRA50 and group 4: DOX + LIRA100; received liraglutide dissolved in normal saline, at a dose of 50 and 100 μg/kg, respectively, s.c., once daily for one week before starting DOX injection and continued for 2 weeks concurrently with DOX (Abbas and Kabil, 2017; Briyal et al., 2014; Deng et al., 2018)
• group 5: LIRA50 and group 6: LIRA100; received liraglutide at a dose of 50 and 100 μg/kg, respectively, s.c., once daily for 3 weeks.
• On the last day of the experiment, rats were weighed then blood samples were collected via the retro-orbital sinus for the estimation of serum testosterone concentration and serum alkaline phosphatase. Rats were euthanized by cervical dislocation then the testes, seminal vesicles and prostate were immediately removed, washed with ice-cold saline and cleaned from the adhering tissue then weighted
Parameters investigated in this phase
Percentage of sperm progressive motility, Sperm count and Sperm deformity
Histopathological examination of the testis
Serum testosterone
Serum ALP
According to this study, the chosen dose was 100 μg/kg
Part-B; Assessment of the mechanisms underlying liraglutide protection against DOX-induced toxicity: a mechanistic study was conducted in which the liraglutide dose selected for further investigation was based upon the results of the dose finding study. The animals were divided into 4 groups (n=8) as follows:
group 1: CONTROL; received the vehicles (normal saline).
group 2: DOX; received a total cumulative dose of DOX (18 mg/kg, i.p.) dissolved in normal saline, in six equally divided doses, on the 8th, 10th, 12th, 15th, 17th and 19th day from the start of the experiment.
group 3: DOX + LIRA100; received liraglutide at a dose of 100μg/kg, s.c., once daily for one week before starting DOX injection and continued for 2 weeks concurrently with DOX.
group 4: LIRA100; received liraglutide at a dose of 100 μg/kg s.c., once daily for 3 weeks.
Twenty-four hours after the last liraglutide dose, behavioral tests were conducted on all rats. cervical dislocation was performed upon terminating the behavioral tests (Y maze spontaneous alternation test: spontaneous alternation percentage (SAP) and total no. of arm entries (TAE), Step through passive avoidance and then the brains were excised for histopathological examination.
The following parameters were investigated:
1-Autophagy markers: testicular mTOR testicular, Phosphorylated AKT (PAKT) and testicular LC3.
2-Oxidative stress markers: reduced glutathione (GSH) and malondialdehyde (MDA) in testis
3-Apoptotic markers: expression of p53 and caspase-3 activity in the testis
4- Steroidogenic enzymes: 3β-hydroxysteroid dehydrogenase (3β- HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD).
6- SUMMARY AND CONCLUSIONS
Summary
The aim of the current study was to test the modulatory effect of liraglutide against DOX-induced testicular toxicity and the subsequent cognitive impairment in rats and to investigate the possible underlying mechanisms for the potential protection.
Experimental design:
Study was divided into two parts:
Part-A; Screening the protective dose of liraglutide against DOX-induced testicular toxicity: a preliminary dose finding study was conducted using 72 rats to select the optimal dose of liraglutide for the treatment of testicular toxicity induced by DOX in rats. The animals were divided into 6 groups (n=12) as follows
• group 1: CONTROL; received the vehicles (normal saline)
• group 2: DOX; received a total cumulative dose of DOX (18 mg/kg, i.p.) dissolved in normal saline, in six equally divided doses, on the 8th, 10th, 12th, 15th, 17th and 19th day from the start of the experiments(Kabel, 2018).
• group 3: DOX + LIRA50 and group 4: DOX + LIRA100; received liraglutide dissolved in normal saline, at a dose of 50 and 100 μg/kg, respectively, s.c., once daily for one week before starting DOX injection and continued for 2 weeks concurrently with DOX (Abbas and Kabil, 2017; Briyal et al., 2014; Deng et al., 2018)
• group 5: LIRA50 and group 6: LIRA100; received liraglutide at a dose of 50 and 100 μg/kg, respectively, s.c., once daily for 3 weeks.
• On the last day of the experiment, rats were weighed then blood samples were collected via the retro-orbital sinus for the estimation of serum testosterone concentration and serum alkaline phosphatase. Rats were euthanized by cervical dislocation then the testes, seminal vesicles and prostate were immediately removed, washed with ice-cold saline and cleaned from the adhering tissue then weighted
Parameters investigated in this phase
Percentage of sperm progressive motility, Sperm count and Sperm deformity
Histopathological examination of the testis
Serum testosterone
Serum ALP
According to this study, the chosen dose was 100 μg/kg
Part-B; Assessment of the mechanisms underlying liraglutide protection against DOX-induced toxicity: a mechanistic study was conducted in which the liraglutide dose selected for further investigation was based upon the results of the dose finding study. The animals were divided into 4 groups (n=8) as follows:
group 1: CONTROL; received the vehicles (normal saline).
group 2: DOX; received a total cumulative dose of DOX (18 mg/kg, i.p.) dissolved in normal saline, in six equally divided doses, on the 8th, 10th, 12th, 15th, 17th and 19th day from the start of the experiment.
group 3: DOX + LIRA100; received liraglutide at a dose of 100μg/kg, s.c., once daily for one week before starting DOX injection and continued for 2 weeks concurrently with DOX.
group 4: LIRA100; received liraglutide at a dose of 100 μg/kg s.c., once daily for 3 weeks.
Twenty-four hours after the last liraglutide dose, behavioral tests were conducted on all rats. cervical dislocation was performed upon terminating the behavioral tests (Y maze spontaneous alternation test: spontaneous alternation percentage (SAP) and total no. of arm entries (TAE), Step through passive avoidance and then the brains were excised for histopathological examination.
The following parameters were investigated:
1-Autophagy markers: testicular mTOR testicular, Phosphorylated AKT (PAKT) and testicular LC3.
2-Oxidative stress markers: reduced glutathione (GSH) and malondialdehyde (MDA) in testis
3-Apoptotic markers: expression of p53 and caspase-3 activity in the testis
4- Steroidogenic enzymes: 3β-hydroxysteroid dehydrogenase (3β- HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD).
6- SUMMARY AND CONCLUSIONS
Summary
The aim of the current study was to test the modulatory effect of liraglutide against DOX-induced testicular toxicity and the subsequent cognitive impairment in rats and to investigate the possible underlying mechanisms for the potential protection.
Experimental design:
Study was divided into two parts:
Part-A; Screening the protective dose of liraglutide against DOX-induced testicular toxicity: a preliminary dose finding study was conducted using 72 rats to select the optimal dose of liraglutide for the treatment of testicular toxicity induced by DOX in rats. The animals were divided into 6 groups (n=12) as follows
• group 1: CONTROL; received the vehicles (normal saline)
• group 2: DOX; received a total cumulative dose of DOX (18 mg/kg, i.p.) dissolved in normal saline, in six equally divided doses, on the 8th, 10th, 12th, 15th, 17th and 19th day from the start of the experiments(Kabel, 2018).
• group 3: DOX + LIRA50 and group 4: DOX + LIRA100; received liraglutide dissolved in normal saline, at a dose of 50 and 100 μg/kg, respectively, s.c., once daily for one week before starting DOX injection and continued for 2 weeks concurrently with DOX (Abbas and Kabil, 2017; Briyal et al., 2014; Deng et al., 2018)
• group 5: LIRA50 and group 6: LIRA100; received liraglutide at a dose of 50 and 100 μg/kg, respectively, s.c., once daily for 3 weeks.
• On the last day of the experiment, rats were weighed then blood samples were collected via the retro-orbital sinus for the estimation of serum testosterone concentration and serum alkaline phosphatase. Rats were euthanized by cervical dislocation then the testes, seminal vesicles and prostate were immediately removed, washed with ice-cold saline and cleaned from the adhering tissue then weighted
Parameters investigated in this phase
Percentage of sperm progressive motility, Sperm count and Sperm deformity
Histopathological examination of the testis
Serum testosterone
Serum ALP
According to this study, the chosen dose was 100 μg/kg
Part-B; Assessment of the mechanisms underlying liraglutide protection against DOX-induced toxicity: a mechanistic study was conducted in which the liraglutide dose selected for further investigation was based upon the results of the dose finding study. The animals were divided into 4 groups (n=8) as follows:
group 1: CONTROL; received the vehicles (normal saline).
group 2: DOX; received a total cumulative dose of DOX (18 mg/kg, i.p.) dissolved in normal saline, in six equally divided doses, on the 8th, 10th, 12th, 15th, 17th and 19th day from the start of the experiment.
group 3: DOX + LIRA100; received liraglutide at a dose of 100μg/kg, s.c., once daily for one week before starting DOX injection and continued for 2 weeks concurrently with DOX.
group 4: LIRA100; received liraglutide at a dose of 100 μg/kg s.c., once daily for 3 weeks.
Twenty-four hours after the last liraglutide dose, behavioral tests were conducted on all rats. cervical dislocation was performed upon terminating the behavioral tests (Y maze spontaneous alternation test: spontaneous alternation percentage (SAP) and total no. of arm entries (TAE), Step through passive avoidance and then the brains were excised for histopathological examination.
The following parameters were investigated:
1-Autophagy markers: testicular mTOR testicular, Phosphorylated AKT (PAKT) and testicular LC3.
2-Oxidative stress markers: reduced glutathione (GSH) and malondialdehyde (MDA) in testis
3-Apoptotic markers: expression of p53 and caspase-3 activity in the testis
4- Steroidogenic enzymes: 3β-hydroxysteroid dehydrogenase (3β- HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD).