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 ofjoint 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 alongwith the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 mg/kg; intraperitoneally). Afterdecapitation on day 16, trunk blood was collected for total oxidant status (TOS) and total antioxidant capacity (TAC) assays. The leftmetatarsophalangeal joint and gastrocnemius muscle were excised for microscopic examination. Muscle samples were also evaluated interms of malondialdehyde (MDA), glutathione, and chemiluminescence (CL) levels.Results: In tadalafil-treated AA rats, metatarsophalangeal joints revealed regular morphology of the cartilage with slight destructionand 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, forMDA; 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, forlucigenin). 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 viasuppression of oxidant generation.