Diabetic nephropathy alters both structure and function of the kidney. These alterations are associated with increased levels of reactive oxygen species, matrix proteins, and proinflammatory molecules. Inflammation decreases gap junctional communication and increases hemichannel activity leading to increased membrane permeability and altering tissue homeostasis. Since current treatments for diabetic nephropathy do not prevent renal damage, we postulated an alternative treatment with boldine, an alkaloid obtained from boldo with antioxidant, anti-inflammatory, and hypoglycemic effects. Streptozotocin-induced diabetic and control rats were treated or not treated with boldine (50？mg/Kg/day) for ten weeks. In addition, mesangial cells were cultured under control conditions or in high glucose concentration plus proinflammatory cytokines, with or without boldine (100？μmol/L). Boldine treatment in diabetic animals prevented the increase in glycemia, blood pressure, renal thiobarbituric acid reactive substances and the urinary protein/creatinine ratio. Boldine also reduced alterations in matrix proteins and markers of renal damage. In mesangial cells, boldine prevented the increase in oxidative stress, the decrease in gap junctional communication, and the increase in cell permeability due to connexin hemichannel activity induced by high glucose and proinflammatory cytokines but did not block gap junction channels. Thus boldine prevented both renal and cellular alterations and could be useful for preventing tissue damage in diabetic subjects. 1. Introduction Diabetic nephropathy (DN) is considered a microvascular complication of diabetes. It is characterized by a chronic injury to renal tissue, mainly glomerular structures. DN is the major complication associated with type I diabetes mellitus, affecting approximately 30–40% of diabetic patients, and is the leading cause of end-stage renal disease [1]. There are several factors involved in the development of diabetic glomerulopathy but the main initiator of this disease is chronic hyperglycemia, which triggers nonenzymatic protein glycosylation and increased production of reactive oxygen species, increasing oxidative stress and favoring coagulation and fibrotic events [2]. Hyperglycemia also sensitizes the vessel wall of efferent arterioles to the action of vasoconstrictors, which, together with an increase in vascular permeability, lead to hyperfiltration. Also, in the progression of DN persistent proteinuria, glomerular hypertrophy, mesangial expansion, and tubulointerstitial fibrosis occur, which lead to
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