Protective effect of irbesartan against doxorubicin-induced nephrotoxicity in rats: implication of AMPK, PI3K/Akt, and mTOR signaling pathways

2018 ◽  
Vol 96 (12) ◽  
pp. 1209-1217 ◽  
Author(s):  
Eman A. Mohamed ◽  
Hebatalla I. Ahmed ◽  
Heba S. Zaky
Keyword(s):  
Protein Kinase ◽  
Protective Effect ◽  
Critical Role ◽  
Mammalian Target Of Rapamycin ◽  
Protective Effects ◽  
Phosphatidylinositol 3 Kinase ◽  
Factor Α ◽  
Amp Activated Protein Kinase ◽  
Renal Expression ◽  
Necrosis Factor

Nephrotoxicity is one of the serious undesirable effects related to doxorubicin (DOX). Herein, we have investigated the potential protective effect of irbesartan (IRB) against chronic nephrotoxicity induced by DOX, and the implication of different mechanistic pathways underlying these effects. Rats were treated with either DOX (2.5 mg/kg i.p., 3 times/week) for 2 weeks, and (or) IRB (40 mg/kg, daily) for 3 weeks. IRB prohibited nephrotoxicity induced by DOX, which was evident by the increase in blood urea nitrogen and creatinine levels and histopathological changes. IRB improved DOX-induced alterations in oxidative status by diminishing lipid peroxidation and upregulating the antioxidant enzymes. Also, upon DOX treatment, the renal expression of tumor necrosis factor-α, interleukin-6, and caspase-3 were significantly increased; IRB diminished DOX-induced alterations in these parameters. Moreover, DOX significantly decreased the expression level of AMP-activated protein kinase (AMPK). Meanwhile, DOX induced activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt/PKB) and mammalian target of rapamycin (mTOR) pathways that cross talked with AMPK. On the contrary, IRB successfully counterbalanced all these effects. Collectively, these outcomes suggest that the modulation of AMPK, PI3K, Akt, and mTOR pathways plays a critical role in conferring the protective effects of IRB against DOX nephrotoxicity.

scholarly journals Antihepatocarcinoma Effect of Portulaca oleracea L. in Mice by PI3K/Akt/mTOR and Nrf2/HO-1/NF-κB Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Zheng Guoyin ◽  
Peng Hao ◽  
Li Min ◽  
Gu Wei ◽  
Chen Zhe ◽  
...  
Keyword(s):  
Nuclear Factor Kappa B ◽  
Mammalian Target Of Rapamycin ◽  
Portulaca Oleracea ◽  
Control Group ◽  
Related Factor ◽  
Protective Effects ◽  
Phosphatidylinositol 3 Kinase ◽  
Pathological Alteration ◽  
Hepatocellular Carcinomas ◽  
Necrosis Factor

The purpose of the present study was to evaluate the pharmacological effects of Portulaca oleracea L. (Purslane) (PL) on N-nitrosodiethylamine- (NDEA-) induced hepatocellular carcinomas (HCC) and explore its potential mechanism. Mice were randomly assigned to four groups: control group, NDEA group, NDEA + Purslane (100 mg/kg) group, and NDEA + Purslane (200 mg/kg) group. The animal of each group was given NDEA (100 ppm) in drinking water. 1 h later, Purslane dissolved in PBS was intragastrically administered for continuous seven days. The results showed that Purslane reduced the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in liver and serum. Purslane also reduced the contents of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), and methane dicarboxylic aldehyde (MDA) and restored the activity of superoxygen dehydrogenises (SOD) in serum. Purslane could obviously attenuate the hepatic pathological alteration. Furthermore, treatment with Purslane effectively inhibited the phosphorylations of phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), nuclear factor-kappa B (NF-κB), and inhibitor of NF-κBα (IκBα) and upregulated the expressions of NF-E2-related factor 2 (Nrf2) and heme oxygenase- (HO-) 1. In conclusion, our research suggested that Purslane exhibited protective effects on NDEA-induced hepatocellular carcinomas by anti-inflammatory and antioxidative properties via the PI3K/Akt/mTOR and Nrf2/HO-1/NF-κB pathway.

scholarly journals Platycodon grandiflorum Saponins Ameliorate Cisplatin-Induced Acute Nephrotoxicity through the NF-κB-Mediated Inflammation and PI3K/Akt/Apoptosis Signaling Pathways

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1328 ◽  
Author(s):  
Weizhe Zhang ◽  
Jingang Hou ◽  
Xiaotong Yan ◽  
Jing Leng ◽  
Rongyan Li ◽  
...  
Keyword(s):  
Protective Effect ◽  
Signaling Pathways ◽  
Kidney Injury ◽  
Dependent Manner ◽  
Protective Effects ◽  
Phosphatidylinositol 3 Kinase ◽  
Platycodon Grandiflorum ◽  
Tnf Α ◽  
Factor Α ◽  
Oxide Synthase

Although cisplatin is a potent chemotherapeutic agent against cancers, its clinical application is seriously limited by its severe side effects of nephrotoxicity. Previous studies reported that saponins isolated from the roots of Platycodon grandiflorum (PGS) exerted protective effects in various animal models of renal injury, with no confirmation on cisplatin-induced injury. This study was designed to investigate the protective effect of PGS (15 and 30 mg/kg) on cisplatin-induced kidney injury in mice. The levels of serum creatinine (CRE) and blood urea nitrogen (BUN), and renal histopathology demonstrated the protective effect of PGS against cisplatin-induced kidney injury. PGS exerted anti-inflammation effects via suppressing nuclear factor-kappa B (NF-κB) activation and alleviating the cisplatin-induced increase in inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in kidney tissues. The expressions of phosphorylation of phosphatidylinositol 3-kinase/protein kinase B and its downstream apoptotic factors, such as Bcl-2 and caspase families were regulated by PGS in a dose-dependent manner. In conclusion, PGS exerted kidney protection effects against cisplatin-induced kidney injury by inhibiting the activation of NF-κB and regulating PI3K/Akt/apoptosis signaling pathways in mice.

scholarly journals Protective Effects of Açai in Combination with Vitamin C against Aluminum-Induced Toxicity in Rat Liver

2017 ◽  
Vol 9 (1) ◽  
pp. 1 ◽  
Author(s):  
Nevien Mahmoud Ahmed ◽  
Fatma A. M. Hamaad
Keyword(s):  
Vitamin C ◽  
Protective Effect ◽  
Control Group ◽  
Protective Effects ◽  
Super Oxide Dismutase ◽  
Biochemical Alterations ◽  
Inflammatory Parameters ◽  
Antioxidant Parameters ◽  
Factor Α ◽  
Necrosis Factor

Aluminum is associated with the pathogenesis of several diseases. Açai has recently emerged as a natural source of antioxidants. The present study was conducted to evaluate the protective effect of Açai in combination with vitamin C against the aluminum chloride induced toxicity. Seventy rats were divided into 7 groups:- Group (GP) 1: control group, GP 2: treated with AlCl3, GP 3: treated with Açai, GP 4: treated with vitamin C, GP 5: treated with AlCl3 and Açai , GP 6: treated with AlCl3 and vitamin C, GP 7: treated with AlCl3, Açai and vitamin C. After 4 weeks, blood and liver specimens were collected to evaluate biochemical alterations and hepatic antioxidant and inflammatory parameters. AlCl3 treatment decreased liver enzymes (alanine aminotransferase, aspartate amino transferase, alkaline phosphatase), tumor necrosis factor-α and IL-6 while hepatic malondialdehyde was elevated. In contrast, hepatic glutathione, super oxide dismutase, catalase were decreased. Açai and vitamin C treatment improved the adverse effects induced by AlCl3, while co-administration with vitamin C promoted the action of açai on hepatic damage and antioxidant parameters. Açai showed a protective effect against AlCl3 induced toxicity, particularly in combination with vitamin C.

Shao-Yang-Xi-Bi-Fang Inhibits Chondrocyte Injury and Inflammation in a Rat Model of Osteoarthritis

2021 ◽  
Vol 20 (2) ◽  
pp. 239-246
Author(s):  
Pengfei Shen ◽  
Bin Wang ◽  
Chong Zheng ◽  
Zikang Xie
Keyword(s):  
Protein Kinase ◽  
Rat Model ◽  
Cell Apoptosis ◽  
Morphological Changes ◽  
Protein Kinase B ◽  
Mammalian Target Of Rapamycin ◽  
Protective Role ◽  
Cycle Arrest ◽  
Factor Α ◽  
Necrosis Factor

In the present study, we have examined the protective role and mechanism of Shao-Yang-Xi-Bi-Fang on osteoarthritis induced chondrocyte injury. We observed (a) upregulation of the expression of miR-15a-5p that was positively associated with cell apoptosis and (b) downregulation of protein kinase B protein and mRNA expression in osteoarthritic tissues. Further studies showed that 3'-untranslated regions of the protein kinase B mRNA were the direct target of the miR-15a-5p. The downregulation of the miR-15a-5p led to upregulation of the protein kinase B and mammalian target of rapamycin expression. The Shao-Yang-Xi-Bi-Fang improved the morphological changes, inhibited cell apoptosis, tumor necrosis factor-α, and interleukin-1β in knee osteoarthritis rat model by inducing cell cycle arrest at G1 phase. Taken together, the Shao-Yang-Xi-Bi-Fang inhibited chondrocyte injury and inflammation in a rat model of osteoarthritis via targeting the miR-15a-5p/protein kinase B pathway, providing a new possible therapeutic regimen to osteoarthritis.

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