Ameliorative effects of clonidine on ethanol induced kidney injury in rats: Potential role for imidazoline-1 receptor

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Abstract

Chronic alcoholism is a risk factor for kidney injury. Clonidine is an α2-adrenergic receptor/imidazoline-1 receptor agonist that can reduce blood pressure and maintain renal functions. This study aims to investigate the possible ameliorative effects of clonidine on ethanol induced kidney injury and its mechanism of action. Kidney injury was induced in rats by adding ethanol to drinking water for eight weeks. Clonidine effects on kidney functions and histopathology were measured. Moreover, phentolamine (α-adrenergic receptor antagonist), efaroxan (imidazoline-1 receptor antagonist) and rilmenidine (imidazoline-1 receptor agonist) were used to clarify the role of imidazoline-1 receptor in mediating renal ameliorative effects. Also, the effect of clonidine on liver functions and metabolic changes, in addition to renal oxidative stress, inflammatory and apoptotic pathways were measured. Results showed that, clonidine improved renal functions and reduced ethanol induced renal inflammation and fibrosis. On the other hand, efaroxan, only, blocked clonidine effects on kidney functions. Rilmenidine decreased kidney injury like clonidine. Both clonidine and rilmenidine increased renal nischarin gene expression. Furthermore, clonidine improved liver functions, increased serum insulin and decreased serum advanced glycation end products (metabolic markers). Also, clonidine reduced renal oxidative stress as reflected by decreased myeloperoxidase, malondialdehyde, inducible nitric oxide synthase and total nitric oxide levels and increased superoxide dismutase level. Moreover, clonidine reduced renal tumor necrosis factor-α (inflammatory marker) and caspase-3 (apoptotic marker) levels, while increased renal prostaglandine E2 and interleukin-10 levels (anti-inflammatory markers). In conclusion, clonidine can reduce ethanol induced kidney injury, at least in part, by stimulating imidazoline-1 receptor signaling.

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