Mid-dose losartan mitigates diabetes-induced hepatic damage by regulating iNOS, eNOS, VEGF, and NF-κB expressions

Fatih Oltulu,Aylin Buhur,Altuğ Yavaşoğlu,Nefise Ülkü Karabay Yavaşoğlu,Timur Köse,Gökçe Ceren Kuşçu,Melih Dağdevi̇ren,Çevik Gürel

doi:10.3906/sag-1901-15

Fatih Oltulu, Aylin Buhur + Show 6 more

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https://doi.org/10.3906/sag-1901-15

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Background/aimLosartan, an antihypertensive drug, is highly preferred in patients with diabetes mellitus (DM) and hypertension because of its retarding effect on diabetic nephropathy. In this study, we investigated the potential therapeutic effect of different doses of losartan on hepatic damage in a streptozotocin (STZ, 50 mg/kg)-induced DM model in rats.Materials and methodsIn this study, five different groups were formed: control, DM, low-dose losartan (5 mg/kg), mid-dose losartan (20 mg/kg), and high-dose losartan (80 mg/kg). Liver tissues of experimental groups were evaluated immunohistochemically for TUNEL, iNOS, eNOS, VEGF, and NF-κB pathways. In addition to immunohistochemical analysis, analyses of SOD and MDA, which are oxidative stress markers, were also performed and the results were evaluated together.ResultsWhen biochemical and immunohistochemical findings were evaluated together, it was found that the results obtained from the mid-dose losartan group were closer to those of the control than the other groups.ConclusionThis study indicated that mid-dose losartan administration may have a therapeutic effect by inhibiting apoptosis and regulating iNOS, eNOS, VEGF, and NF-κB protein expressions in DM-induced hepatic damage.

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This study indicated that mid-dose losartan administration may have a therapeutic effect by inhibiting apoptosis and regulating inducible NOS (iNOS), endothelial NOS (eNOS), vascular endothelial growth factor (VEGF), and Nuclear factor κB (NF-κB) protein expressions in Diabetes mellitus (DM)-induced hepatic damage
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by increased blood glucose level, hyperglycemia, and glucosuria, which are usually caused by deficiency in insulin secretion and/or insulin hormone activity in the pancreatic beta cells [1,2]
reactive nitrogen species (ROS) production and oxidative stress induced by hyperglycemia enhance Nitric oxide (NO) formation in diabetic liver damage

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Introduction

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by increased blood glucose level, hyperglycemia, and glucosuria, which are usually caused by deficiency in insulin secretion and/or insulin hormone activity in the pancreatic beta cells [1,2]. Chronic hyperglycemia arising from untreated DM can cause damage to several organs such as the eyes, kidneys, heart, and liver [3]. Nitric oxide (NO) is an important signaling molecule produced by three different nitric oxide synthase (NOS) isoforms: neuronal NOS (nNOS; NOS1), inducible NOS (iNOS; NOS2) and endothelial NOS [5]. It is known that VEGF has a fibrinogenic effect on the liver via the triggering of inflammation and the stimulation of endothelial and stellate cells [13]

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