Effect of phosphodiesterase-5 inhibition on joint and muscle damage in rats with adjuvant arthritis

Abstract

Background/aim: This study was designed to examine the effect of tadalafil, a phosphodiesterase (PDE)5 inhibitor, on the severity of joint and muscle damage in rats with adjuvant-induced arthritis (AA). Materials and methods: AA was induced by intradermal inoculation into right hind paw of male Sprague Dawley rats (300-450g) with complete Freund's adjuvant (CFA; 0.1 mL). AA rats were treated with either tadalafil (10 mg/kg; per oral) alone or along with the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 mg/kg; intraperitoneally). After decapitation on day 16, trunk blood was collected for total oxidant status (TOS) and total antioxidant capacity (TAC) assays. The left metatarsophalangeal joint and gastrocnemius muscle were excised for microscopic examination. Muscle samples were also evaluated in terms of malondialdehyde (MDA), glutathione, and chemiluminescence (CL) levels. Results: In tadalafil-treated AA rats, metatarsophalangeal joints revealed regular morphology of the cartilage with slight destruction and less inflammatory cell infiltration and vascularization in comparison to the controls (microscopic score: 1.17 ± 0.31 vs. 4.17 ± 0.79; P < 0.01). AA rats presented increased gastrocnemius muscle MDA, glutathione, and CL levels compared to the controls (P < 0.01, for MDA; P < 0.05, for glutathione; P < 0.05 for CL). Tadalafil attenuated the increase in CL levels (P < 0.01, for luminol and P < 0.001, for lucigenin). Serum TOS showed significant reductions by tadalafil. Conclusion: The long-acting PDE5 inhibitor tadalafil provides partial protection in a rat model of CFA-induced arthritis possibly via suppression of oxidant generation.

Aliskiren, tadalafil, and cinnamaldehyde alleviate joint destruction biomarkers; MMP-3 and RANKL; in complete Freund's adjuvant arthritis model: Downregulation of IL-6/JAK2/STAT3 signaling pathway

“…The analgesic effect of tadalafil on zymosan-induced arthritis has been explored to be associated with reduced neutrophil infiltration and TNF-α ( Rocha et al, 2011 ), which was in accordance with our results. Moreover, tadalafil has been demonstrated to partially protect against arthritis induced by CFA through the improvement of oxidant/antioxidant balance, but its effects on MMP-3, RANKL, and the inflammatory signaling haven't been investigated ( Bahadir et al, 2018 ). The reduction in MMP-3 level could be attributed to the increased cGMP due to PDE-5 inhibition by tadalafil, where PDE-5 inhibition by sildenafil has been evidenced to inhibit the production of MMPs ( Sun et al, 2010 , Kuno et al, 2011 ).…”

“…( Abd El-Raouf et al, 2015 ), tadalafil (10 mg/kg/day; p.o.) ( Bahadir et al, 2018 ), and aliskiren (20 mg/kg/day; p.o.) ( Zhao et al, 2020 ), respectively.…”

Molecular Basic of Pharmacotherapy of Cytokine Imbalance as a Component of Intervertebral Disc Degeneration Treatment

“…The analgesic effect of tadalafil on zymosan-induced arthritis was associated with a decrease in neutrophil infiltration and a decrease in TNF-α levels [325]. Tadalafil partially protects against arthritis caused by collagen induction by improving the balance between oxidants and antioxidants [326]. The tadalafil-mediated decrease in MMP-3 levels may be associated with an increase in cGMP levels due to PDE-5 inhibition by tadalafil [327].…”