Abstract: SA-PO100
Alpha-7 Nicotinic Receptor Agonist GTS-21 Ameliorates Contrast-Induced Nephropathy in Rats
Session Information
- AKI: Mechanisms - Primary Injury and Repair - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Akcay, Seckin, Marmara University Medical Faculty, Istanbul, Turkey
- Ozdemir, Zarife, Marmara University Medical Faculty, Istanbul, Turkey
- Cilingir-Kaya, Ozlem T., Marmara University Medical Faculty, Istanbul, Turkey
- Peker, Irem, Marmara University Medical Faculty, Istanbul, Turkey
- Akkiprik, Mustafa, Marmara University Medical Faculty, Istanbul, Turkey
- Yegen, Berrak, Marmara University Medical Faculty, Istanbul, Turkey
- Koc, Mehmet, Marmara University Medical Faculty, Istanbul, Turkey
Background
Despite the extensive use of contrasts in medicine, no proven pharmacological therapies exist to prevent contrast-induced nephropathy (CIN), which causes renal damage by renal vasoconstriction, medullary hypoxia, oxidative stress and direct tubular toxicity of the contrast agent. In an experimental CIN model, we aimed to evaluate the possible therapeutic effects of GTS-21, a selective alpha-7 nicotinic receptor agonist with anti-apoptotic, anti-inflammatory and anti-oxidative properties.
Methods
In male Sprague-Dawley rats, CIN was induced by intravenous injection of indomethacin (10 mg/kg), L-NAME (10 mg/kg) and a high-osmolar contrast agent (Urografin 76%, 6 ml/kg). Starting at 24 h before CIN induction, every 12 hours, rats were injected intraperitoneally with saline (contrast, n=14) or GTS-21 (GTS-21-contrast, 4 mg/kg, n=10), while the control groups with no CIN induction were treated with saline (control, n=8) or GTS-21 (GTS-21-control, n=8). At the 48th h of CIN, blood and kidney samples were obtained for the determination of cytokine expression (RT-PCR), oxidative stress parameters and histopathological analysis. Data were analyzed using ANOVA and Student’s t-test.
Results
When compared to control and GTS-21-control groups, serum creatinine and BUN levels in the contrast group were elevated (p<0.05), while these measurements in GTS-21-contrast group were not different than controls. Increased histopathological damage score in contrast group (p<0.01) with respect to both control groups was significantly decreased in GTS-21-contrast group (p<0.001). Elevated malondialdehyde level in contrast group (p<0.001) was partially lowered by GTS-21 treatment, while antioxidant glutathione level was increased (p<0.05). In both contrast groups, an increase in IL-6 expression and a reduction in TGF-β expression were observed (p<0.05), but GTS-21 treatment increased TGF-β expression (p <0.05) and slightly depressed IL-6 expression.
Conclusion
GTS-21 improves renal dysfunction and provides a significant protection against contrast nephropathy via anti-oxidant and anti-inflammatory mechanisms.