Role of Quercetin and L-arginine in Alleviating Zinc Oxide Nanoparticle Hepatotoxicity in Rats

NA Abdel Baky1, LM Fadda1, NM Al-Rasheed1, NM Al-Rasheed1, W Shebely2. 1College of Pharmacy,King Saud University, Pharmacology Dep., Saudi Arabia, 2Faculty of Medicine,King Saud University, Department of Anatomy and stem cell unit, Saudi Arabia

Purpose

The rapid growth of the nanotechnology industry has led to the wide-scale production and application of engineered nanoparticles (NPs). The purpose of this study is to evaluate the toxicity of oral exposure to zinc oxide nano-particles (ZnO-NPs) on liver tissue of rats, and the hepatoprotective effect of quercetin (Qur) and/or L-arginine (Arg) against such ZnO-NPs –induced hepatotoxicity.

Method

ZnO-NPs were administered orally in two doses (either 600 mg/Kg or 1g/Kg body weight/day for 5 consecutive days) to male Wister albino rats weighing 170-200 g (10 rats/group). In order to detect the protective effects of the studied antioxidants against ZnO-NPs induced hepatotoxicity, biomarkers of metabolic disorder, tissue damage and inflammation, as well as oxidative deoxyribonucleic acid (DNA) damage were investigated. Data are presented as the mean ± S.D. One way analysis of variance (ANOVA) followed by Bonferroni multiple tests was used to determine the differences between means of different groups. The level of significance was set at p ≤ 0.05.

Results

Co-administration of Qur (200mg/Kg body weight) and/or Arg (200mg/Kg body weight) daily for three weeks to ZnO–NPs intoxicated rats, significantly down-modulated the dramatic alteration in the investigated biochemical parameters. Where, the significant increase in serum alanine amino transferase (ALT) level (139.8±1.2 in ZnO intoxicated group vs. 126.06±1.05 U/L in normal group, P<0.001), the level of the pro-inflammatory biomarkers including tumor necrosis factor- α(TNF-α) (371.7±6.1 in ZnO intoxicated group vs. 242.7±6.1 pg/ml in normal group, P<0.001), interleukin-6 (IL-6) (49.57±1.01 in ZnO intoxicated group vs. 31±2.098 pg/ml in normal group, P<0.001), C-reactive protein (CRP) (4.6±0.11 in ZnO intoxicated group vs. 3.16±0.1 ng/ml in normal group, P<0.001), and immunoglobin g (IGg) (168.5±0.55 in ZnO intoxicated group vs. 131.9±1.15 ng/ml in normal group, P<0.001), were significantly decreased in treated group as compared to intoxicated rats. Furthermore, the studied antioxidants either alone or in combination effectively ameliorated the hepatic oxidative damage in DNA induced by of ZnO-NPs as confirmed by comet assay (percentage of DNA in tail 2.11±3.08 in combination group vs.3.05± 0.49 in ZnO intoxicated group, P<0.001).

Conclusion

These results support the use of Qur and Arg as protective agents against metal oxide nanoparticles hepatotoxicity, with their combination achieving a powerful hepatoprotective action.