Renoprotective Effect of Pitavastatin against TAA-Induced Renal Injury: Involvement of the miR-93/PTEN/AKT/mTOR Pathway

Author:

Elbaset Marawan A.1ORCID,Mohamed Bassim M. S. A.1ORCID,Moustafa Passant E.1ORCID,Esatbeyoglu Tuba2ORCID,Afifi Sherif M.3,Hessin Alyaa F.1ORCID,Abdelrahman Sahar S.4ORCID,Fayed Hany M.1ORCID

Affiliation:

1. Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt

2. Department of Molecular Food Chemistry and Food Development, Institute of Food Science and Human Nutrition, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, Hannover 30167, Germany

3. Pharmacognosy Department, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt

4. Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt

Abstract

This research investigated if pitavastatin (Pita) might protect rats’ kidneys against thioacetamide (TAA). By altering the PTEN/AKT/mTOR pathway, pitavastatin may boost kidney antioxidant capacity and minimize oxidative damage. Statins have several benefits, including antioxidant and anti-inflammatory characteristics. The principal hypothesis of this study was that Pita can regulate the miR-93/PTEN/AKT/mTOR pathways, which is thought to be responsible for its renoprotective effects. The experiment divided male rats into four groups. Group 1 included untreated rats as the control. Group 2 included rats which received TAA (100 mg/kg intraperitoneally thrice a week for two weeks) to destroy their kidneys. Groups 3 and 4 included rats which received Pita orally at 0.4 and 0.8 mg/kg for 14 days after TAA injections. Renal injury increased BUN, creatinine, and MDA levels and decreased glutathione (GSH) levels. Pitavastatin prevented these alterations. TAA decreased PTEN and increased miR-93, Akt, p-Akt, mTOR, and Stat3 in the kidneys. Pitavastatin also regulated the associated culprit pathway, miR-93/PTEN/Akt/mTOR. In addition, TAA induced adverse effects on the kidney tissue, which were significantly ameliorated by pitavastatin treatment. The findings suggest that pitavastatin can attenuate renal injury, likely by regulating the miR-93/PTEN/Akt/mTOR pathway. This modulation of the pathway appears to contribute to the protective effects of pitavastatin against TAA-induced renal injury, adding to the growing evidence of the pleiotropic benefits of statins in renal health.

Funder

Gottfried Wilhelm Leibniz Universität Hannover

Publisher

Hindawi Limited

Subject

Pharmacology (medical),Organic Chemistry,General Pharmacology, Toxicology and Pharmaceutics,Biochemistry

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