Pelin Aydin1,2, Zeynep Berna Aksakalli Magden3, Sevgi Karabulut Uzuncakmak4, Hamza Halici3,5, Nurullah Akgun3, Ali Sefa Mendil6, Behzad Mokhtare7, Elif Cadirci3. 1. Department of Anesthesiology and Reanimation, Educational and Research Hospital, Erzurum, Turkey. dr.paydin@hotmail.com. 2. Department of Pharmacology, Faculty of Medicine, Ataturk University, Ataturk University Campus, Ataturk District, Erzurum, 25240, Yakutiye, Turkey. dr.paydin@hotmail.com. 3. Department of Pharmacology, Faculty of Medicine, Ataturk University, Ataturk University Campus, Ataturk District, Erzurum, 25240, Yakutiye, Turkey. 4. Department of Health Services Vocational School, Bayburt University, Bayburt, Turkey. 5. Department of Hınıs Vocational Training School, Ataturk University, Erzurum, Turkey. 6. Department of Pathology, Faculty of Veterinary Medicine, Erciyes University, Kayseri, Turkey. 7. Department of Pathology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey.
Abstract
AIM: We demonstrate the effect of PDE5 inhibitors in cases of acute lung injury via the relationship between cGMP/NO and the TLR4-NF-κB-NLRP3 pathway. MATERIALS AND METHODS: This study was performed with 30 male Wistar albino rats. Lipopolysaccharide (LPS) was administered intratracheally to the rats and acute lung injury (ALI) was induced. Twelve hours after LPS administration, avanafil, prepared at suitable doses according to the body weights of the animals, was administered by oral gavage. Lung tissue samples of all groups were examined histopathologically and by immunochemical staining (IL-1β, iNOS, TLR4, and NF-κB). The iNOS, NLRP3, and IL-1B mRNA expression levels in the lung tissues were measured by RT-PCR. The left upper lobes of the rat lungs were dried at 70 °C for 48 h and lung water content was calculated. RESULT: Statistically significant increases in iNOS, NLRP3, and IL-1β mRNA expressions were observed in the rats with ALI compared to the healthy controls (p < 0.0001). Those increased expressions were reduced at both doses of avanafil (p < 0.0001). This reduction was found to be greater at 20 mg/kg (p < 0.0001). IL-1β, iNOS, TLR4, and NF-κB immunopositivity was moderate/severe in the ALI group and mild in the group with ALI + avanafil at 20 mg/kg (p < 0.05). When the wet/dry lung ratios were calculated, a statistically significant increase was seen in the ALI group compared to the healthy rats (p < 0.05). That increase was decreased with both avanafil doses (p < 0.05). CONCLUSION: We suggest that avanafil may prevent the progression of ALI and be effective in its treatment. We hope that this study will be supported by future clinical studies to yield a new indication for avanafil.
AIM: We demonstrate the effect of PDE5 inhibitors in cases of acute lung injury via the relationship between cGMP/NO and the TLR4-NF-κB-NLRP3 pathway. MATERIALS AND METHODS: This study was performed with 30 male Wistar albino rats. Lipopolysaccharide (LPS) was administered intratracheally to the rats and acute lung injury (ALI) was induced. Twelve hours after LPS administration, avanafil, prepared at suitable doses according to the body weights of the animals, was administered by oral gavage. Lung tissue samples of all groups were examined histopathologically and by immunochemical staining (IL-1β, iNOS, TLR4, and NF-κB). The iNOS, NLRP3, and IL-1B mRNA expression levels in the lung tissues were measured by RT-PCR. The left upper lobes of the rat lungs were dried at 70 °C for 48 h and lung water content was calculated. RESULT: Statistically significant increases in iNOS, NLRP3, and IL-1β mRNA expressions were observed in the rats with ALI compared to the healthy controls (p < 0.0001). Those increased expressions were reduced at both doses of avanafil (p < 0.0001). This reduction was found to be greater at 20 mg/kg (p < 0.0001). IL-1β, iNOS, TLR4, and NF-κB immunopositivity was moderate/severe in the ALI group and mild in the group with ALI + avanafil at 20 mg/kg (p < 0.05). When the wet/dry lung ratios were calculated, a statistically significant increase was seen in the ALI group compared to the healthy rats (p < 0.05). That increase was decreased with both avanafil doses (p < 0.05). CONCLUSION: We suggest that avanafil may prevent the progression of ALI and be effective in its treatment. We hope that this study will be supported by future clinical studies to yield a new indication for avanafil.
Authors: Kenneth P Steinberg; Leonard D Hudson; Richard B Goodman; Catherine Lee Hough; Paul N Lanken; Robert Hyzy; B Taylor Thompson; Marek Ancukiewicz Journal: N Engl J Med Date: 2006-04-20 Impact factor: 91.245
Authors: Gordon D Rubenfeld; Ellen Caldwell; Eve Peabody; Jim Weaver; Diane P Martin; Margaret Neff; Eric J Stern; Leonard D Hudson Journal: N Engl J Med Date: 2005-10-20 Impact factor: 91.245
Authors: P Kosutova; P Mikolka; S Balentova; M Kolomaznik; M Adamkov; J Mokry; A Calkovska; D Mokra Journal: J Physiol Pharmacol Date: 2019-01-21 Impact factor: 3.011