L- Thyroxine ameliorates renal function in thyroidectomized diabetic nephropathy rats through downregulation of TGF- β1, Ang II and ET-1 expression

Abstract

ABSTRACT Thyroidectomy is the gold standard in treating cancer thyroid patients. Thyroidectomy patients are more susceptible to type 2 diabetes mellitus (T2DM) development. T2DM is a major health problem worldwide, due to its chronic associated complications. Diabetic nephropathy (DN) is one of the most detrimental complications. Moreover, thyroidectomy could increase kidney injury incidence and hypothyroidism either clinical or subclinical frequently coincides with T2DM, significantly associated with DN occurrence and severity, however the exact mechanism still unclear and it is the aim of this study to explore the pathogenesis involved in Thyroidectomy mediated nephrotoxicity, besides assessing the therapeutic role of L-thyroxine on nephropathy. Using biochemical and histopathological techniques, glucose homeostasis, lipid profile, kidney architecture, function, transforming growth β1 (TGF- β1), angiotensin II (Ang II) and Endothelin (ET)-1 markers were investigated in type 2 diabetic rats with or without thyroidectomy and after L-thyroxine treatment. Data revealed that thyroidectomy impaired glucose tolerance, adversely affected the lipid profile, induced nephropathy and deteriorated kidney function significantly compared to the control and T2DM groups (proteinuria, 118.5 ± 16.2 versus 10.3 ± 1.6 and 118.5 ± 16.2 versus 102.2 ± 9.2). Moreover, L-thyroxine could ameliorate hyperglycemia, dyslipidemia, renal morphology and function compared to thyroidectomy group (proteinuria 51.1 ± 3.4 versus 118.5 ± 16.2), which was mediated by TGF-β1, Ang II and ET-1. This could be a guide to use L-thyroxine supplementation in thyroidectomy patients, especially if associated with T2DM to avoid or slow down nephropathy development.