Biomedicine and pharmacotherapeutic effectiveness of combinatorial atorvastatin and quercetin on diabetic nephropathy: An in vitro study - 27/04/24
, Ashwini Prabhu b , Pavan S.R b, Sourav Mohanto c , Vetriselvan Subramaniyan d, ⁎ Abstract |
Introduction |
Diabetic nephropathy is a type of kidney disorder that develops as a complication of multifactorial diabetes. Diabetic nephropathy is characterized by microangiopathy, resulting from glucose metabolism, oxidative stress, and changes in renal hemodynamics. This study strived to evaluate the in vitro cytoprotective activity of atorvastatin (ATR), and quercetin (QCT) alone and in combination against diabetic nephropathy.
Methods |
The MTT assay was utilized to analyze the effects of the test compounds on NRK-52E rat kidney epithelial cells. The detection of apoptosis and ability to scavenge free radicals was assessed via acridine orange-ethidium bromide (AO-EB) dual fluorescence staining, and 2,2-diphenyl-1-picrylhydrazyfree assay (DPPH), respectively. The ability of anti-inflammatory effect of the test compounds and western blot analysis against TGF-β, TNF-α, and IL-6 further assessed to determine the combinatorial efficacy.
Results |
Atorvastatin and quercetin treatment significantly lowered the expression of TGF-β, TNF-α, and IL-6 indicating the protective role in Streptozotocin-induced nephrotoxicity. The kidney cells treated with a combination of atorvastatin and quercetin showed green fluorescing nuclei in the AO-EB staining assay, indicating that the combination treatment restored cell viability. Quercetin, both alone and in combination with atorvastatin, demonstrated strong DPPH free radical scavenging activity and further encountered an anti-oxidant and anti-inflammatory effect on the combination of these drugs.
Conclusion |
Nevertheless, there is currently no existing literature that reports on the role of QCT as a combination renoprotective drug with statins in the context of diabetic nephropathy. Hence, these findings suggest that atorvastatin and quercetin may have clinical potential in treating diabetic nephropathy.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Diabetic nephropathy, a consequence of multifactorial metabolic syndrome with increased inflammatory markers. |
• | ATR treatment reduced renal cell apoptosis and downregulated the expressions of inflammatory and apoptotic markers. |
• | QCT reduces inflammation, ROS, and cell death, thereby protecting renal function. |
• | First mechanistic evidence of QCT+ATR in diabetic nephropathy treatment. |
• | ATR+QCT reduce oxidative stress, alleviate cytotoxicity, and prevent apoptosis against STZ-induced nephrotoxicity. |
Abbreviations : ATR, QCT, HMG-CoA, STZ, CKD, TGF-β, ECM, IL-6, TNF-α, FN, DMEM, FBS, HRP, DPPH, MTT, DMSO, AE-BO., PBS, AO-EB, AA, TAC, FRAP, TBS, ROS
Keywords : Diabetes, Nephropathy, Quercetin, Atorvastatin, Streptozotocin, Inflammation
Plan
Vol 174
Article 116533- mai 2024 Retour au numéro
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