Amelioration of aluminum-induced hepatic and nephrotoxicity by Premna odorata extract is mediated by lowering MMP9 and TGF-β gene alterations in Wistar rat

Abstract

This study aims to investigate the effect of Premna odorata (P. odorata) (Lamiaceae) on the hepatic and nephrotoxicity induced by aluminum chloride (AlCl3) in rat. Wistar male rats were equally classified into four groups: control, P. odorata extract (500 mg/kg B.W.), AlCl3 (70 mg/kg B.W.), and P. odorata extract plus AlCl3 groups. All treatments were given orally for 4 weeks. Serum transaminases and some biochemical parameters, hepatic and renal antioxidant/oxidant biomarker; tumor necrosis factor-α (TNF-α); matrix metalloproteinase (MMP9) and transforming growth factor-β (TGF-β) mRNA expression; histopathological examination of the liver, and kidneys were investigated. The obtained results revealed that AlCl3 significantly increased the activities of serum aspartate transaminase, alanine transaminase, and alkaline phosphatase as well as produced a significant increase in total cholesterol, triglyceride, urea, and creatinine concentrations, while there were no changes observed in the total protein, albumin, and globulin concentrations. Also, aluminum administration significantly decreased the reduced glutathione content and increased the catalase activity, malondialdehyde, and TNF-α concentrations in the liver and kidney tissue. Moreover, AlCl3 results in congestion, degeneration, and inflammation of the liver and kidney tissue. Co-treatment of P. odorata extract with AlCl3 alleviated its harmful effects on the previous parameters and reduced the histopathological alterations induced by AlCl3. Therefore, Premna odorata may have a potent protective effect against oxidative stress induced by Al toxicity through downregulation of MMP9 and TGF-β gene expression.

Gum Arabic Mitigates AlCl3-Induced Nephrotoxicity by Upregulating the XRCC1 Gene and Downregulating Ki67 and P53 Expressions

“…However, the changes caused by the treatment with AlCl 3 were significantly reversed when GA was administered to the AlCl 3 -treated group. Additionally, MDA levels were found to be higher and GSH levels to be lower by Al Dera, [12] and Othman et al, [29] and Ahmed et al [30] The results on the effects of GA on SOD, GSH, and MDA provided more understanding of the antioxidant potentials of GA reported in several previous studies. [27,31] Base excision repair and the repair of a single-strand break in DNA are both carried out by the X-ray repair crosscomplementing 1 (XRCC1) gene.…”

Nephroprotective effects of silymarin and its fabricated nanoparticles against aluminum‐induced oxidative stress, hyperlipidemia, and genotoxicity

“…In this work, TNF‐α, TGF‐β, and MMP9 gene expression were significantly elevated by AlCl 3 in kidney tissues. In similarity, AlCl 3 intoxication was reported to induce these inflammatory processes leading to renal cell apoptosis 66,103,104 …”

“…In similarity, AlCl 3 intoxication was reported to induce these inflammatory processes leading to renal cell apoptosis. 66,103,104 Regarding the histopathological examination, the kidney tissue of rats treated with AlCl 3 underwent a number of pathological changes in glomeruli and urinary tubules. AlCl 3 severely altered Malpighian corpuscles causing them to lose their characteristic shape which may be due to its oxidative toxicity.…”

Bromelain Modulates Liver Injury, Hematological, Molecular, and Biochemical Perturbations Induced by Aluminum via Oxidative Stress Inhibition

“…It has been discovered that human tissue inflammation increases MMP expression. MMPs have a role in the regulation of inflammatory mediators, which attract immune cells to injured tissues [ 84 , 85 ]. The observed downregulation in the Nrf2 gene's expression level in the hepatic tissues of AlCl 3 -intoxicated rats is consistent with findings made by Yu et al [ 86 ] and Othman et al [ 87 ], who discovered that Nrf2 deregulation is linked to Al toxicity.…”