Preprint Article Version 1 This version is not peer-reviewed

Boldine Improves Kidney Damage in the Goldblatt 2K1C Model Avoiding the Increase in TGF-β

Version 1 : Received: 14 May 2018 / Approved: 17 May 2018 / Online: 17 May 2018 (07:50:15 CEST)

A peer-reviewed article of this Preprint also exists.

Gómez, G.I.; Velarde, V. Boldine Improves Kidney Damage in the Goldblatt 2K1C Model Avoiding the Increase in TGF-β. Int. J. Mol. Sci. 2018, 19, 1864. Gómez, G.I.; Velarde, V. Boldine Improves Kidney Damage in the Goldblatt 2K1C Model Avoiding the Increase in TGF-β. Int. J. Mol. Sci. 2018, 19, 1864.

Journal reference: Int. J. Mol. Sci. 2018, 19, 1864
DOI: 10.3390/ijms19071864

Abstract

Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of kidney damage in Renovascular hypertension (RVH). The activation of the Renin-Angiotensin System (RAS) is crucial in the development and progression of hypertensive renal damage and TGF-β is closely associated with the activation of RAS. In the present study, we assessed the effect of boldine on the progression of kidney disease using the 2K1C hypertension model and identifying mediators in the RAS such as TGF-β, that could be modulated by this alkaloid. Toward this hypothesis, rats (n=5/group) were treated with boldine (50mg/kg/day, gavage) for 6 weeks after 2K1C surgery (pressure≥180mmHg). Kidney function was evaluated by measuring of proteinuria/creatininuria ratio (U prot/U Crea), oxidative stress (OS) by measuring thiobarbituric acid reactive substances (TBARS). The evolution of systolic blood pressure (SBP) was followed weekly. α-SMA and Col III were used as markers of kidney damage; ED-1 and Osteopontin (OPN) as markers of inflammation. We also explored the effect in RAS mediators, such as ACE-1 and TGF-β. Boldine treatment reduced UProt/UCrea ratio, plasma TBARS and slightly reduced SBP in 2K1C hypertensive rats, producing no effect in control animals. In 2K1C rats treated with boldine the levels of α-SMA, Col III, ED-1 and OPN were lower when compared to 2K1C rats. Boldine prevented the increase in ACE-1 and TGF-β in 2K1C rats, suggesting that boldine reduces kidney damage. These results suggest that boldine could potentially be used as a nutraceutic.

Subject Areas

renovascular hypertension; chronic kidney disease; oxidative stress; fibrosis; (S)-2,9-dihydroxy-1,10-dimethoxy-aporphine

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