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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.

Aluminium is a ubiquitous element that occurs naturally in the soil making human exposure to it unavoidable. It is implicated in the aetiology of different neurodegenerative diseases and can induce liver injury. In addition, insulin resistance (IR) plays an essential role in the pathogenesis and the progression of liver disorders. The increased consumption of fructose contained in soft drinks and western pattern diet results in IR that along with the wide distribution of aluminium make the concurrent exposure conceivable and increase the risk of liver injury. Therefore, the present study explores the hepatotoxic effects of aluminium and fructose administered concurrently and evaluates the possible protection by monoammonium glycyrrhizinate (MAG). Liver injury was induced by the administration of aluminium chloride (34 mg/kg/d) plus 10% (w/v) fructose in drinking water. Male rats were treated with either MAG (40 mg/kg/d) or silymarin (SIL, 100 mg/kg/d). The concurrent administration of aluminium and fructose (FRUAL) induced liver injury manifested as a significant elevation of serum liver enzymes activities, bilirubin level, and prothrombin time, as well as reduction of albumin level. On the other hand, the administration of MAG improved the FRUAL-induced aberrations of liver function tests and hepatic cytoarchitecture. We assume that the MAG-induced suppression of oxidative stress, toll-like receptor 4 pathway activation, inflammation, and apoptosis might play a crucial role in the hepatoprotective effect of MAG in this model. Intriguingly, the hepatoprotective effect MAG against FRUAL-induced liver injury surpasses that of the gold standard SIL, suggesting MAG as a better alternative to SIL., (© 2020 John Wiley & Sons Australia, Ltd.)

Aluminum is implicated in the etiology of different neurodegenerative diseases, diabetes and cancer. The current study was conducted to evaluate the protective effects of glycyrrhizic acid (GAM) and silymarin (SLY) on AlCl 3 -induced neurotoxicity in insulin resistant rats. Insulin resistance (IR) was induced by fructose (10%) in drinking water for 18 weeks. Rats received AlCl 3 (34 mg/kg/day) with or without fructose, GAM (40 mg/kg/day), or SLY (100 mg/kg/day). The administration of GAM or SLY suppressed AlCl 3 -induced memory deficit, oxidative stress, and neuroinflammation in brain tissue of IR rats. Both agents inhibited AlCl 3 -induced activation of TLR4 signaling pathway including the downstream activation of NF-κB. The results show that IR can partly exacerbate AlCl 3 -induced neurotoxicity, particularly memory deficit and neuroinflammation. In addition, GAM and SLY showed promising neuroprotective effect against AlCl 3 -induced brain damage in IR rats. The neuroprotection induced by these natural products might be mediated through their antioxidant and anti-inflammatory effects. The latter effect seems to be mediated via inhibition of TLR4 signaling pathway providing new insights on the mechanisms implicated in AlCl 3 -induced neurotoxicity and the neuroprotection afforded by GAM and SLY.