Enhanced renoprotective actions of Paricalcitol and omega-3 fatty acids co-therapy against diabetic nephropathy in rat

• Published in: Journal of advanced research 2022-05, Vol.38, p.119-129
• Main Authors: El-Boshy, Mohamed, Alsaegh, Aiman, Qasem, Ahmed H., Sindi, Ramya A., Abdelghany, Abdelghany H., Gadalla, Hossam, Reda, Doha, Azzeh, Firas, Idris, Shakir, Ahmad, Jawwad, Refaat, Bassem
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Basic and Biological Science; Caspase 3 - metabolism; Diabetes Mellitus; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Ergocalciferols; Fatty Acids, Omega-3 - pharmacology; Fatty Acids, Omega-3 - therapeutic use; Female; Humans; Hydrogen Peroxide - metabolism; INOS; KIM-1; Lipocalin-2 - therapeutic use; Male; NGAL; Rats; TGF-β; Transforming Growth Factor beta1 - metabolism; Transforming Growth Factor beta1 - therapeutic use; Vitamin D
• ISSN: 2090-1232; 2090-1224
• DOI: 10.1016/j.jare.2021.08.010

[Display omitted] •Pcal and ω-3 monotherapies moderately attenuated hyperglycaemia and dyslipidaemia.•Pcal and ω-3 monotherapies equally reduced renal oxidative stress and inflammation.•Pcal/ω-3 co-therapy showed enhanced anti-diabetic and renoprotection effects.•Co-therapy may induce boosted metabolic, anti-oxidative & anti-inflammatory actions. Although the synthetic vitamin D analogue, Paricalcitol, and omega-3 Fatty acids (ω-3) alleviated diabetic nephropathy (DN), their combination was not previously explored. This study measured the potential ameliorative effects of single and dual therapies of Paricalcitol and/or ω-3 against DN. Forty rats were assigned as follow: negative (NC) and positive (PC) controls, Paricalcitol, ω-3 and Paricalcitol + ω-3 groups. Diabetes was generated by high-fat/high-fructose diet and a single streptozotocin injection (40 mg/kg). DN was confirmed by raised fasting blood glucose (FBG), polyuria, proteinuria, and decreased urine creatinine levels. Paricalcitol intraperitoneal injections (0.25 µg/Kg/day; 5 times/week) and oral ω-3 (415 mg/kg/day; 5 times/week) started at week-9 and for eight weeks. The PC group showed hyperglycaemia, dyslipidaemia, abnormal renal biochemical parameters, elevated caspase-3 expression, and increased apoptosis by TUNEL technique. The mRNAs and proteins of the pathogenic molecules (TGF-β1/iNOS) and markers of tissue damage (NGAL/KIM-1) augmented substantially in the PC renal tissues relative to the NC group. The oxidative stress (MDA/H2O2/protein carbonyl groups) and pro-inflammatory (IL1β/IL6/TNF-α) markers increased, whereas the anti-inflammatory (IL10) and anti-oxidative (GSH/GPx1/GR/SOD1/CAT) declined, in the PC renal tissues. The monotherapy groups were associated with ameliorated FBG, lipid profile and renal functions, and diminished TGF-β1/iNOS/NGAL/KIM-1/Caspase-3 alongside the apoptotic index than the PC group. The oxidative stress and pro-inflammatory markers decreased, whilst the anti-oxidative and anti-inflammatory molecules escalated, in the monotherapy groups than the PC group. Although the Paricalcitol renoprotective actions were better than ω-3, all the biomarkers were abnormal than the NC group. Alternatively, the Paricalcitol + ω-3 protocol exhibited the best improvements in metabolic control, renal functions, oxidative stress, inflammation, and apoptosis. However, FBG and tissue damage were persistently higher in the co-therapy group than controls. Both monotherapies showed mode