Impact of stress and protein malnutrition on the potential role of epigallocatechin-3-gallate in providing protection from nephrotoxicity and hepatotoxicity induced by aluminum in rats

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Author: 
Azza A. Ali, Mona G. Khalil, Hemat A. Elariny and Shereen S. Elshaer
Subject Area: 
Health Sciences
Abstract: 

Background: Aluminum (Al) is very abundant metal in the earth’s crust. It is a constituent of cooking utensils, medicines, cosmetics, some foods and food additives. Salts of Al are widely used in the treatment of drinking water for purification purposes. Excessive and prolonged exposure to Al causes oxidative stress and impairment of many physiological functions. Its accumulation in liver and kidney causes hepatotoxicity and nephrotoxicity. Social isolation (SI) or Protein malnutrition (PM) also increases oxidative stress and may enhance the toxicity of Al as well as the degeneration in liver and kidney. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and has strong antioxidant as well as anti-inflammatory activities and can protect against oxidative stress-induced degenerations. Objective: To study the influence of stress or PM on Al-induced nephrotoxicity and hepatotoxicity in rats, as well as on the potential role of EGCG in providing protection. Methods: Rats received daily AlCl3 (70 mg/kg, IP) for three weeks (Al-toxicity groups) except one normal control group received saline. Al-toxicity groups were divided into four treated and four untreated groups; treated rats received EGCG (10 mg/kg, IP) together with AlCl3. One group of both treated and untreated rats served as control for each of them and the others were subjected to either stress (mild using isolation or high using electric shock) or to PM (10% casein diet). Specimens of liver and kidney were used for assessment of inflammatory mediators (TNF-α, IL-6β, NF-κB), oxidative stress (MDA, SOD, TAC, NO), Caspase-3 and for DNA fragmentation as well as for histopathological examinations. Biochemical changes were also measured in the serum as cholesterol, triglycerides, HDL, albumin, total bilirubin, glucose, creatinine and urea as well as the levels of ALT, AST and ALP. Results: Nephrotoxicity and hepatotoxicity induced by Al were enhanced in rats exposed to PM as well as to stress, the influence of stress especially high stress was more pronounced as indicated by the increase in liver and kidney MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3, DNA fragmentation and in serum ALT, AST, ALP, cholesterol, triglycerides, total bilirubin, glucose, creatinine and urea levels, together with the decrease in HDL, albumin, SOD and TAC. EGCG provided protection against hazards of Al as indicated by the decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation as well as in levels of ALT, AST, ALP, cholesterol, triglycerides, total bilirubin, glucose, creatinine and urea, together with the increase in HDL, albumin, SOD and TAC that is confirmed by histopathological examinations. It provided more pronounced protection in high stressful conditions than in mild one than in PM. Conclusion: Stress have bad impact on Al-induced nephrotoxicity and hepatotoxicity more than PM, thus it can clarify and maximize the role of EGCG in providing protection. Consequently, administration of EGCG is advised with excessive Al-exposure to avoid nephrotoxicity and hepatotoxicity especially in populations more subjected to stress or PM.

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