Involvement of redox status and the nuclear-related factor 2 in protecting against cadmium-induced renal injury with Sana Makki (Cassia senna L.) pre-treatment in male rats

Abstract

This study was designed to investigate the potential defensive strategy of Sana Makki extract (SME) against Cd-induced in vivo nephrotoxicity and its underlying mechanisms. Male albino rats were used in a thirty days study comparing control, SMEtreated, CdCl 2 -treated, and combined SME and Cd treatment. Pre-treatment with SME signifi cantly reduced serum kidney biomarkers (urea and creatinine), the concentration of renal KIM-1, and kidney index values. Additionally, SME also attenuated CdCl 2 -induced oxidative and nitrosative stress in renal tissue; signifi cantly reducing malondialdehyde (MDA) and nitric oxide (NO) concentrations and signifi cantly increasing antioxidant enzymes in kidney tissue. Molecularly, SME signifi cantly upregulated antioxidant gene expression (SOD2, GR, GPx1, and CAT) caused by Cd. Notably, the augmented mRNA expression of nuclear-related factor 2 (Nrf2) by Cd was enhanced by SME administration. SME markedly suppressed the Cd-induced rise in pro-infl ammatory cytokines. The combination of Cd and SME relieved the Cd-induced apoptotic damage by enhancing Bcl2 and suppressing Bax and Cas-3 levels in renal tissue. The renal tissue histoarchitecture confi rmed the biochemical and molecular fi ndings. Collectively, our data indicate that SME can counteract Cd-induced renal intoxication through anti-oxidative, antiinfl ammatory, and anti-apoptotic mechanisms.

Candesartan Protects Against Cadmium-Induced Hepatorenal Syndrome by Affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1–7 Signals

“…In parallel to kidney biomarker investigation, we observed injurious effects, including degeneration, necrosis, inflammatory infiltrates, and increased fibrous tissue amount in histopathologically examined kidney tissues. In consistency with other studies, degenerative effects and distortion of renal histoarchitecture were observed by other authors [ 17 , 41 ]. On the other side, we found that candesartan potently ameliorated injurious effects on the liver and the kidney caused by Cd toxicity.…”

Anchoring of Nanocomposites Based on Novel Metal Nanocomplexes/Nanocarbonaceous Surfaces and Assessing Their In Vivo Anticancer Effects on Ehrlich Ascites Tumor

“…The free Nrf2 then travels to the nucleus, where it binds to the ARE and activates antioxidant enzyme-coding targets. 49 …”

“…The Nrf2 transcription factor is activated by oxidative stress when it is released from the Nrf2/keap1 complex. The free Nrf2 then travels to the nucleus, where it binds to the ARE and activates antioxidant enzyme-coding targets …”

Oxidative Stress and Its Role in Cd-Induced Epigenetic Modifications: Use of Antioxidants as a Possible Preventive Strategy

“…The alterations of these enzymes by Cd are given by the fact that this metal can change the enzymatic topography fundamental for the catalytic function of the enzymes [97], replace the metals that are part of the active centers of enzymes [18,98], or deplete the cofactors necessary for functioning; for example, selenium depletion due to the formation of the Cd-Se-Cys complex decreases GPx activity [18,[99][100][101]. In addition, Cd indirectly decreases the concentration of antioxidant enzymes by altering the expression of Nrf2 [102][103][104]. Another important mechanism via which Cd generates OS is the decrease in antioxidant defenses, which both direct and indirect interactions achieve.…”