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. 2024 Jan 23:2024:6681873.
doi: 10.1155/2024/6681873. eCollection 2024.

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

Marawan A Elbaset  1 , Bassim M S A Mohamed  1 , Passant E Moustafa  1 , Tuba Esatbeyoglu  2 , Sherif M Afifi  3 , Alyaa F Hessin  1 , Sahar S Abdelrahman  4 , Hany M Fayed  1
Affiliations

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

Marawan A Elbaset et al. Adv Pharmacol Pharm Sci. .

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.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Effect of pitavastatin on serum renal function: (a) urea and (b) creatinine. A bar shows the mean and standard error of six rats: ∗compared to the normal control group, @to the TAA group, and #to pita (0.4 mg/kg) at p < 0.05. Pita: pitavastatin and TAA: thioacetamide.
Figure 2
Figure 2
Effect of pitavastatin on renal (a) MDA and (b) GSH. A bar shows the mean and standard error of six rats: compared ∗to the normal control group and @to the TAA group at p < 0.05. Pita: pitavastatin and TAA: thioacetamide.
Figure 3
Figure 3
Effect of pitavastatin on (a) AKT, (b) p-AKT, (c) p-AKT/AKT, (d) mTOR, (e) p-mTOR, (f) p-mTOR/m-TOR, and (g) PTEN. A bar shows the mean and standard error of six rats: ∗compared to the normal control group, @to the TAA group, and #to pita (0.4 mg/kg) at p < 0.05. Pita: pitavastatin and TAA: thioacetamide.
Figure 4
Figure 4
Effect of pitavastatin on renal gene expression of (a) miR-93 and (b) AKT. A bar shows the mean and standard error of six rats: ∗compared to the normal control group, @to the TAA group, and #to pita (0.4 mg/kg) at p < 0.05. Pita: pitavastatin and TAA: thioacetamide.
Figure 5
Figure 5
Effect of p on histopathology findings. Normal control (a), TAA group (b–d), low dose of pitavastatin-treated groups (e–f), and high dose of the pitavastatin-treated group (g–h).
Figure 6
Figure 6
Effect of pitavastatin on Stat3 expression in kidney tissues. (a) Normal group, (b) TAA group, (c) low dose of Pita, and (d) high dose of Pita. A bar shows the mean and standard error of six rats: compared ∗to the normal control group and @to the TAA group at p < 0.05. Pita: pitavastatin and TAA: thioacetamide.
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