•Effects of sildenafil on isoniazid and streptomycin neurotoxicity in rats

Abstract

Objectives: Neurotoxicity due to isoniazide (INH) and streptomycin has been reported. Experimental studies reported that sildenafil can reduce toxic effects of some drugs. The aim of this study was to investigate the possible toxic effects of long-term streptomycin and INH use and probable protective effects of sildenafil on the rat brain and cerebellum. Materials and methods: In this study, 78 rats were divided into eight groups as follows; control group (n=10), INH group (n=10), streptomycin group (n=10), INH + streptomycin group (n=10), sildenafil group (n=10), INH+sildenafil group (n=10), streptomycin+sildenafil group (n=8) and INH+streptomycin + sildenafil group (n=10). At the end of 30 days of the treatment, the brain and cerebellar tissues of the rats were examined histopathologically. On the all tissues, inflammation, edema, congestion, degeneration and necrosis were investigated under a light microscope by the same pathologist blinded to the experimental groups. Results: Degeneration was significantly more prominent in the streptomycin group compared with the control group (respectively, p=0.002, p<0.001) on the cerebellum and cerebrum of the rats. INH+streptomycin group showed increased degenerative changes in the brain tissues compared with the INH group (p=0.006). Cerebellar degeneration on the INH+streptomycin+sildenafil group was the most obvious when compared to the control group (p=0.001) and degenerative changes was more obvious in the INH+streptomycin+sildenafil group when compared to the INH+streptomycin group (p=0.032). Conclusion: INH and streptomycin combination showed increased neurotoxicity in the rats. However, sildenafil worsened this neurotoxicity. Electron microscopic and immunohistochemical further studies are needed to investigate some aspects of this toxicity.