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The effect of testosterone and endurance training on signaling pathways in the rat spinal cord
Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45
29
IL-17A and IL-17F gene polymorphism are not the important factors associated with susceptibility and some clinical parameters of RA in a Polish population.
Materials and methods: 24 male Wistar rats receiving normal diet were used in the experiment. On Day 1 rats were divided randomly in two groups:
http://dx.doi.org/10.1016/j.pharep.2015.06.087
1. Group P – rats receiving pantoprazole (3 mg/kg) 2. Group C (control group) – rats receiving saline solution
The effect of testosterone and endurance training on signaling pathways in the rat spinal cord Andrzej Małecki 1,*, Katarzyna Nierwin´ska 1, Anna Pudełko 2, Jo´zef Langfort 1, Marta Nowacka 1 1
The Jerzy Kukuczka Academy of Physical Education in Katowice, Katowice, Poland 2 Department of Pharmacology, Medical University of Silesia, Katowice, Poland *Corresponding author. [email protected]
We have estimated the impact of two doses of testosterone on the signaling pathways in rat spinal cord and BDNF, VEGF and heat shock protein (Hsp70) in the rat spinal cord. Adult male Wistar rats were trained using a motor-driven treadmill for 6 weeks (40–60 min 5 times a week) and/or were treated (6 wks) with two doses of testosterone (i.m.; 8 mg/kg or 80 mg/kg body weight). Spinal cords were collected 48 hours after the last training cycle and stored at 80 8C. Proteins employed in signaling pathways (p-Akt, PKC, pERK1/2, p-p38) as well as BDNF, VEGF-A, VEGF-C and HSP70 levels were measured using Western blot method in whole tissue lysates of spinal cord. Some of the effects of the endurance training and testosterone may be associated with increased signal transmission associated with nitric oxide and protein kinase systems. Endurance training, testosterone (8 mg/kg) and their combination increased VEGF-A and decreased VEGF-C levels. The higher dose of testosterone reduced both isoforms of VEGF. Endurance training could only partially offset the adverse effects of high doses of testosterone. Training used separately did not affect the amount of BDNF in spinal cord tissue homogenates. The higher dose of testosterone used alone and combined with endurance training led to decrease in BDNF protein. Obtained results suggest, that excessive supply of testosterone may cause undesirable influence on the spinal cord. http://dx.doi.org/10.1016/j.pharep.2015.06.088 Influence of pantoprazole, a proton-pump inhibitor, on serum calcium and phosphate levels in rats Agnieszka Matuszewska *, Beata Nowak, Anna Merwid-La˛d, Marta Szandruk, Joanna Kwiatkowska, Małgorzata Pies´niewska, Adam Szela˛g Department of Pharmacology, Medical University, Wrocław, Poland *Corresponding author. Background: Proton-pump inhibitors (PPIs) belong to wildly used drugs. Epidemiological studies revealed, that long-term therapy with PPIs increases risk of vertebral and hip fractures [Yu EW et al., Am J Med, 2011]. Maintaining proper bone mass depends among others on calcium-phosphate homeostasis. Aims: The aim of the study was top evaluate influence of pantoprazole, a proton-pump inhibitor, on serum calcium and phosphate levels in rats.
Saline solution and pantoprazole were given intraperitoneally once daily for 84 days. On Day 85 blood samples were collected. Serum calcium and phosphate levels were assessed in certified laboratory. Results: Serum calcium level was significantly decreased in rats receiving pantoprazole comparing to control group (9.6250 0.5463 mg/dl vs. 10.1545 0.3778 mg/dl, p = 0.014). No significant difference in serum phosphate levels between analyzed groups was detected (4.9083 0.7154 mg/dl in group P vs. 5.0636 1.2118 mg/ dl in group C, p > 0.05). No significant differences between analyzed groups in age and body weight on Day 85 were detected. Summary: Long-term therapy with pantoprazole may lead to decrease in serum calcium level. http://dx.doi.org/10.1016/j.pharep.2015.06.089 Impact of carvedilol on ADMA–DDAH pathway and IL1-beta level after single dose cyclophosphamide administration in rat model Anna Merwid-La˛d *, Małgorzata Trocha, Ewa Chlebda-Sieragowska, Marta Szandruk, Beata Nowak, Tomasz Sozan´ski, Małgorzata Pies´niewska, Adam Szela˛g Department of Pharmacology, Wroclaw Medical University, Wrocław, Poland *Corresponding author. Cyclophosphamide-induced (CPX) tissue damages are connected to the induction of oxidative stress and proinflammatory cytokines in tissues. This may influence ADMA level and DDAH activity. Carvedilol is considered as strong antioxidant. The aim of this study was to check impact of carvedilol on CPX-induced changes in ADMA/DDAH pathway and IL1-beta concentration. Male rats were given single intraperitoneal dose of 200 mg/kg of cyclophosphamide. Carvedilol was given once daily at a dose of 2 mg/kg by gastric tube a day before, at the day and one day after CPX injection. Intraperitoneal injections of mesna (200 mg/kg) were done 20 min before, 4 and 8 h after CPX administration, divided into 20%, 40% and 40% doses, respectively. Rats in experimental groups received as follows: C – normal saline, X – CPX, MX – CPX + mesna, VX – CPX + carvedilol, MVX – CPX + mesna + carvedilol. Levels of ADMA in serum and IL1-beta in kidney were measured using ELISA kit. DDAH activity was determined spectrophotometrically in liver. Serum ADMA level was significantly increased in X group in comparison to the control. This action of CPX was significantly reversed only in groups receiving mesna (MX and MVX), but not in the group receiving carvedilol alone. DDAH activity was comparable in all studied groups and any significant differences were noticed. In VX group kidney concentration of IL1-beta was significantly lower than in all other groups. IL1-beta level was decreased also in MVX group and in comparison to the control group the difference was on significance border (p = 0.057). In conclusion only mesna decreases ADMA, but only carvedilol decreases IL1-beta level, what requires further studies. http://dx.doi.org/10.1016/j.pharep.2015.06.090
29
IL-17A and IL-17F gene polymorphism are not the important factors associated with susceptibility and some clinical parameters of RA in a Polish population.
Materials and methods: 24 male Wistar rats receiving normal diet were used in the experiment. On Day 1 rats were divided randomly in two groups:
http://dx.doi.org/10.1016/j.pharep.2015.06.087
1. Group P – rats receiving pantoprazole (3 mg/kg) 2. Group C (control group) – rats receiving saline solution
The effect of testosterone and endurance training on signaling pathways in the rat spinal cord Andrzej Małecki 1,*, Katarzyna Nierwin´ska 1, Anna Pudełko 2, Jo´zef Langfort 1, Marta Nowacka 1 1
The Jerzy Kukuczka Academy of Physical Education in Katowice, Katowice, Poland 2 Department of Pharmacology, Medical University of Silesia, Katowice, Poland *Corresponding author. [email protected]
We have estimated the impact of two doses of testosterone on the signaling pathways in rat spinal cord and BDNF, VEGF and heat shock protein (Hsp70) in the rat spinal cord. Adult male Wistar rats were trained using a motor-driven treadmill for 6 weeks (40–60 min 5 times a week) and/or were treated (6 wks) with two doses of testosterone (i.m.; 8 mg/kg or 80 mg/kg body weight). Spinal cords were collected 48 hours after the last training cycle and stored at 80 8C. Proteins employed in signaling pathways (p-Akt, PKC, pERK1/2, p-p38) as well as BDNF, VEGF-A, VEGF-C and HSP70 levels were measured using Western blot method in whole tissue lysates of spinal cord. Some of the effects of the endurance training and testosterone may be associated with increased signal transmission associated with nitric oxide and protein kinase systems. Endurance training, testosterone (8 mg/kg) and their combination increased VEGF-A and decreased VEGF-C levels. The higher dose of testosterone reduced both isoforms of VEGF. Endurance training could only partially offset the adverse effects of high doses of testosterone. Training used separately did not affect the amount of BDNF in spinal cord tissue homogenates. The higher dose of testosterone used alone and combined with endurance training led to decrease in BDNF protein. Obtained results suggest, that excessive supply of testosterone may cause undesirable influence on the spinal cord. http://dx.doi.org/10.1016/j.pharep.2015.06.088 Influence of pantoprazole, a proton-pump inhibitor, on serum calcium and phosphate levels in rats Agnieszka Matuszewska *, Beata Nowak, Anna Merwid-La˛d, Marta Szandruk, Joanna Kwiatkowska, Małgorzata Pies´niewska, Adam Szela˛g Department of Pharmacology, Medical University, Wrocław, Poland *Corresponding author. Background: Proton-pump inhibitors (PPIs) belong to wildly used drugs. Epidemiological studies revealed, that long-term therapy with PPIs increases risk of vertebral and hip fractures [Yu EW et al., Am J Med, 2011]. Maintaining proper bone mass depends among others on calcium-phosphate homeostasis. Aims: The aim of the study was top evaluate influence of pantoprazole, a proton-pump inhibitor, on serum calcium and phosphate levels in rats.
Saline solution and pantoprazole were given intraperitoneally once daily for 84 days. On Day 85 blood samples were collected. Serum calcium and phosphate levels were assessed in certified laboratory. Results: Serum calcium level was significantly decreased in rats receiving pantoprazole comparing to control group (9.6250 0.5463 mg/dl vs. 10.1545 0.3778 mg/dl, p = 0.014). No significant difference in serum phosphate levels between analyzed groups was detected (4.9083 0.7154 mg/dl in group P vs. 5.0636 1.2118 mg/ dl in group C, p > 0.05). No significant differences between analyzed groups in age and body weight on Day 85 were detected. Summary: Long-term therapy with pantoprazole may lead to decrease in serum calcium level. http://dx.doi.org/10.1016/j.pharep.2015.06.089 Impact of carvedilol on ADMA–DDAH pathway and IL1-beta level after single dose cyclophosphamide administration in rat model Anna Merwid-La˛d *, Małgorzata Trocha, Ewa Chlebda-Sieragowska, Marta Szandruk, Beata Nowak, Tomasz Sozan´ski, Małgorzata Pies´niewska, Adam Szela˛g Department of Pharmacology, Wroclaw Medical University, Wrocław, Poland *Corresponding author. Cyclophosphamide-induced (CPX) tissue damages are connected to the induction of oxidative stress and proinflammatory cytokines in tissues. This may influence ADMA level and DDAH activity. Carvedilol is considered as strong antioxidant. The aim of this study was to check impact of carvedilol on CPX-induced changes in ADMA/DDAH pathway and IL1-beta concentration. Male rats were given single intraperitoneal dose of 200 mg/kg of cyclophosphamide. Carvedilol was given once daily at a dose of 2 mg/kg by gastric tube a day before, at the day and one day after CPX injection. Intraperitoneal injections of mesna (200 mg/kg) were done 20 min before, 4 and 8 h after CPX administration, divided into 20%, 40% and 40% doses, respectively. Rats in experimental groups received as follows: C – normal saline, X – CPX, MX – CPX + mesna, VX – CPX + carvedilol, MVX – CPX + mesna + carvedilol. Levels of ADMA in serum and IL1-beta in kidney were measured using ELISA kit. DDAH activity was determined spectrophotometrically in liver. Serum ADMA level was significantly increased in X group in comparison to the control. This action of CPX was significantly reversed only in groups receiving mesna (MX and MVX), but not in the group receiving carvedilol alone. DDAH activity was comparable in all studied groups and any significant differences were noticed. In VX group kidney concentration of IL1-beta was significantly lower than in all other groups. IL1-beta level was decreased also in MVX group and in comparison to the control group the difference was on significance border (p = 0.057). In conclusion only mesna decreases ADMA, but only carvedilol decreases IL1-beta level, what requires further studies. http://dx.doi.org/10.1016/j.pharep.2015.06.090