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

Abstract

Background/aim:

Losartan, 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 methods:

In 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.

Results:

When 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.

Conclusion:

This 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.

• Authors: Fatih Oltulu, Aylin Buhur, Çevik Gürel, Gökçe Cerren Kuşçu, Melih Dağdeviren, Nefise Ülkü Karabay Yavaşoğlu, Timur Köse, Altuğ Yavaşoğlu
• Journal: Turkish journal of medical sciences (Turk J Med Sci) Vol. 49 Issue 5 Pg. 1582-1589 (Oct 24 2019) ISSN: 1303-6165 [Electronic] Turkey
• PMID: 31652041 (Publication Type: Journal Article)
• Copyright: This work is licensed under a Creative Commons Attribution 4.0 International License.

Chemical References

• Antihypertensive Agents
• NF-kappa B
• Vascular Endothelial Growth Factor A
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Nos2 protein, rat
• Nos3 protein, rat
• Losartan

Topics

• Animals
• Antihypertensive Agents (administration & dosage)
• Diabetes Complications (prevention & control)
• Diabetes Mellitus, Experimental (metabolism)
• Liver Diseases (prevention & control)
• Losartan (administration & dosage)
• Male
• NF-kappa B (biosynthesis, drug effects)
• Nitric Oxide Synthase Type II (biosynthesis, drug effects)
• Nitric Oxide Synthase Type III (biosynthesis, drug effects)
• Rats
• Rats, Wistar
• Vascular Endothelial Growth Factor A (biosynthesis, drug effects)