Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus
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Published:2023-12-12
Issue:24
Volume:24
Page:17380
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Mujalli Abdulrahman1ORCID, Farrash Wesam F.1ORCID, Obaid Ahmad A.1ORCID, Khan Anmar A.1, Almaimani Riyad A.2ORCID, Idris Shakir1, Elzubier Mohamed E.2ORCID, Khidir Elshiekh Babiker A.1ORCID, Aslam Akhmed1ORCID, Minshawi Faisal1ORCID, Alobaidy Mohammad A.3ORCID, Alharbi Adel B.1ORCID, Almasmoum Hussain A.1ORCID, Ghaith Mazen1, Alqethami Khalid4ORCID, Refaat Bassem1ORCID
Affiliation:
1. Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia 2. Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia 3. Department of Anatomy, Faculty of Medicine, Umm AlQura University, Makkah P.O. Box 7607, Saudi Arabia 4. Department of Laboratory, Al-Noor Specialist Hospital, Makkah P.O. Box 7607, Saudi Arabia
Abstract
Herein, we measured the antidiabetic and nephroprotective effects of the sodium–glucose cotransporter-2 inhibitor (empagliflozin; SGLT2i) and synthetic active vitamin D (paricalcitol; Pcal) mono- and co-therapy against diabetic nephropathy (DN). Fifty mice were assigned into negative (NC) and positive (PC) control, SGLT2i, Pcal, and SGLT2i+Pcal groups. Following establishment of DN, SGLT2i (5.1 mg/kg/day) and/or Pcal (0.5 µg/kg/day) were used in the designated groups (5 times/week/day). DN was affirmed in the PC group by hyperglycaemia, dyslipidaemia, polyuria, proteinuria, elevated urine protein/creatinine ratio, and abnormal renal biochemical parameters. Renal SREBP-1 lipogenic molecule, adipokines (leptin/resistin), pro-oxidant (MDA/H2O2), pro-inflammatory (IL1β/IL6/TNF-α), tissue damage (iNOS/TGF-β1/NGAL/KIM-1), and apoptosis (TUNEL/Caspase-3) markers also increased in the PC group. In contrast, renal lipolytic (PPARα/PPARγ), adiponectin, antioxidant (GSH/GPx1/SOD1/CAT), and anti-inflammatory (IL10) molecules decreased in the PC group. Both monotherapies increased insulin levels and mitigated hyperglycaemia, dyslipidaemia, renal and urine biochemical profiles alongside renal lipid regulatory molecules, inflammation, and oxidative stress. While SGLT2i monotherapy showed superior effects to Pcal, their combination demonstrated enhanced remedial actions related to metabolic control alongside renal oxidative stress, inflammation, and apoptosis. In conclusion, SGLT2i was better than Pcal monotherapy against DN, and their combination revealed better nephroprotection, plausibly by enhanced glycaemic control with boosted renal antioxidative and anti-inflammatory mechanisms.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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