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Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus.
Mujalli, Abdulrahman; Farrash, Wesam F; Obaid, Ahmad A; Khan, Anmar A; Almaimani, Riyad A; Idris, Shakir; Elzubier, Mohamed E; Khidir, Elshiekh Babiker A; Aslam, Akhmed; Minshawi, Faisal; Alobaidy, Mohammad A; Alharbi, Adel B; Almasmoum, Hussain A; Ghaith, Mazen; Alqethami, Khalid; Refaat, Bassem.
Afiliación
  • Mujalli A; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
  • Farrash WF; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
  • Obaid AA; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
  • Khan AA; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
  • Almaimani RA; Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
  • Idris S; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
  • Elzubier ME; Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
  • Khidir EBA; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
  • Aslam A; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
  • Minshawi F; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
  • Alobaidy MA; Department of Anatomy, Faculty of Medicine, Umm AlQura University, Makkah P.O. Box 7607, Saudi Arabia.
  • Alharbi AB; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
  • Almasmoum HA; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
  • Ghaith M; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
  • Alqethami K; Department of Laboratory, Al-Noor Specialist Hospital, Makkah P.O. Box 7607, Saudi Arabia.
  • Refaat B; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Al Abdeyah, Makkah P.O. Box 7607, Saudi Arabia.
Int J Mol Sci ; 24(24)2023 Dec 12.
Article en En | MEDLINE | ID: mdl-38139208
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 (IL1ß/IL6/TNF-α), tissue damage (iNOS/TGF-ß1/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.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 / Nefropatías Diabéticas / Dislipidemias / Inhibidores del Cotransportador de Sodio-Glucosa 2 / Hiperglucemia Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Arabia Saudita
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 / Nefropatías Diabéticas / Dislipidemias / Inhibidores del Cotransportador de Sodio-Glucosa 2 / Hiperglucemia Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Arabia Saudita