Cadmium-induced adrenal cortical autophagy in rats: possible modulation by sildenafil

Abstract

BACKGROUND: The link between autophagy, inflammatory bowel disease, ischaemic injury and cancer had been established. Reasonable evidence is available for cadmium to be related to certain cancers. Sildenafil had been investigated to modulate oxidative stress mechanisms. The aim of this study is to investigate cadmium-induced adrenal cortical autophagy and to declare possible modulation by sildenafil. MATERIALS AND METHODS: Twenty four Wistar rats weighing 150-200 g were randomly and equally assigned into: control group, sildenafil (20 mg/kg/day orally) exposed group, cadmium group (cadmium chloride 1 mg/kg/day SC), cadmium + sildenafil group (rats received cadmium concomitant with sildenafil). Euthanasia was done 4 weeks from the beginning of experiment; adrenal glands were subjected to biochemical, histological, ultrastructural and immunnohistochemical assessment. RESULTS: Control and sildenafil exposed groups exhibited nearly similar results. Cadmium had produced adrenal cortical apoptosis and ultrastructural derangement of cell organelles. Cadmium-induced autophagy was detected by ultrastructural abundance of enlarged lysosomes and significant (p < 0.05) increase in the optical density of lysosomal associated membrane protein 2 immunoexpression. Sildenafil taken with cadmium had decreased adrenal cortical autophagy, significantly modulated the adrenal gland superoxide dismutase and malondialdehyde compared to cadmium group. Also, the optical density of nuclear factor kappa B (NF-kB) and caspase-3 immunoexpression was significantly decreased in cadmium + sildenafil compared to cadmium group. CONCLUSIONS: Cadmium might induce adrenal cortical autophagy in rats and sildenafil might show an ameliorating effect probably through enhancement of antioxidant defence mechanism and modulation of NF-kB.