The renoprotective effect of glycyrrhizic acid in insulin-resistant rats exposed to aluminum involves the inhibition of
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ORIGINAL ARTICLE
The renoprotective effect of glycyrrhizic acid in insulin-resistant rats exposed to aluminum involves the inhibition of TLR4/NF-κB signaling pathway Noha A. Emara 1 & Mona F. Mahmoud 1 & Hassan M. El Fayoumi 1 & Amr A. A. Mahmoud 1,2 Received: 20 August 2020 / Accepted: 29 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Aluminum is well recognized as a nephrotoxic agent. Its hazardous effects arise from the high risk of daily exposure. The consumption of fructose also represents a critical health issue that might negatively impact different organs, including the kidneys. To pursue our previous work, this study aimed to investigate the potential renoprotective effects of glycyrrhizic acid (GLYA) on aluminum-induced nephrotoxicity in insulin-resistant rats. Insulin resistance (IR) was induced by adding fructose (10%) in drinking water for 18 weeks. Male Wistar rats were divided into five groups: control (CTRL), aluminum chloride (ALM, 34 mg/kg/day), fructose (FRCT), aluminum plus fructose (AL/FR), and GLYA (rats received AL/FR and treated with 40 mg/kg GLYA daily). AL/FR resulted in abnormal renal function tests and renal tissue injury. This was associated with increased oxidative stress and inflammation in the renal tissue. Moreover, the expressions of the toll-like receptor 4 (TLR4) and its adaptor proteins were increased in AL/FR group. The administration of GLYA mollified AL/FR-induced renal injury, oxidative stress, activation of the TLR4 signaling pathway, and inflammation. In conclusion, we provide evidence for the promising renoprotective effect of GLYA against AL/FR-induced kidney damage in rats. The renoprotection is attributed to the suppression of oxidative stress and inhibition of the TLR4/NF-κB signaling pathway in the kidneys. Keywords Aluminum . Fructose . Nephrotoxicity . Glycyrrhizic acid . Toll-like receptor 4 . Oxidative stress
Introduction Fructose is a health hazard that is widely used as the main component of the modern diet despite its implication in different organ disorders, including the kidneys. Different studies showed that the consumption of high fructose is implicated in kidney damage (Kizhner and Werman 2002; Nakayama et al. 2010; Aoyama et al. 2012; Oudot et al. 2013). Furthermore, human exposure to aluminum is being increased, particularly in developing countries through the use of utensils made from Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s00210-02002012-y. * Amr A. A. Mahmoud [email protected] 1
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
2
Present address: Department of Pharmacology, Pharmacy Program, Oman College of Health Sciences, 114 Muscat, Oman
aluminum. Aluminum leakage is higher when such utensils are used for cooking salty, alkaline, or acidic foods (Lin et al. 1997). Another important source of aluminum exposure is the use of aluminum-containing phosphate binders for th
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