Aluminium nanoparticles (AL-NPs) caused gastrointestinal malformations, metabolic disorders and steatohepatitis in zebrafish larvae: Modulatory role of rosmarinic acid

Recently, nanomaterials including alumina have been extensively involved in aquaculture for many purposes resulting in potential hazards in fish. However, its effect on the developing metabolic organs and lipid metabolism remains unclear. This study, investigated the effects of aluminium nanoparticles (AL-NPs) on the metabolic organs of the growing zebrafish larvae including intestine, liver, and pancreas in addition to the potential ameliorative role of rosmarinic acid (RA) against AL-NPs - induced toxicity. Briefly, fertilized zebrafish eggs were divided into 4 groups. The 1st group was kept as a control. The 2nd group was exposed to RA (0.5 mg/L). The 3rd group was exposed to AL-NPs (160 mg/L). The 4th group received both RA and AL-NPs at the same concentrations from 1st day post fertilization (dpf) till the 14th dpf. Here, AL-NPs exposed group showed the highest mortality rate, external morphology defects and gastrointestinal malformations after larval-to-juvenile transition. Interestingly, mixing RA to AL-NPs significantly reduced these effects. Additionally, AL-NPs induced intestinal epithelium defects at the histological and genetic levels and abnormal lipid retention via up-regulation of the lipogenesis-related genes and down-regulation of the hepatic fatty acid β-oxidation. However, addition of RA to AL-NPs could reverse these effects. AL-NPs also induce inflammatory response and mediated endoplasmic reticulum ER and cellular oxidative stress indicated by qRT-PCR and western blot analysis which were then be reduced by RA. Collectively, AL-NPs were highly correlated with the induction of steatohepatitis and lipogenesis after the larval-to-juvenile transition and this could be relief in the presence of RA suggesting it as a promising nutrient for fish.