Zinc Oxide Nanoparticles and Vitamin C Ameliorate Atrazine-Induced Hepatic Apoptosis in Rat via CYP450s/ROS Pathway and Immunomodulation

Abstract

Atrazine, as an herbicide, is used widely worldwide. Because of its prolonged persistence in the environment and accumulation in the body, atrazine exposure is a potential threat to human health. The present study evaluated the possible protective effects of zinc oxide nanoparticles and vitamin C against atrazine-induced hepatotoxicity in rats. Atrazine administered to rats orally at a dose of 300 mg/kg for 21 days caused liver oxidative stress as it increased malondialdehyde (MDA) formation and decreased reduced glutathione (GSH) contents. Atrazine induced inflammation accompanied by apoptosis via upregulation of hepatic gene expression levels of NF-κB, TNF-α, BAX, and caspase-3 and downregulation of Bcl-2 gene expression levels. Additionally, it disturbed the metabolic activities of cytochrome P450 as it downregulated hepatic gene expression levels of CYP1A1, CYP1B1, CYP2E1. The liver function biomarkers were greatly affected upon atrazine administration, and the serum levels of AST and ALT were significantly increased, while BWG%, albumin, globulins, and total proteins levels were markedly decreased. As a result of the above-mentioned influences of atrazine, histopathological changes in liver tissue were recorded in our findings. The administration of zinc oxide nanoparticles or vitamin C orally at a dose of 10 mg/kg and 200 mg/kg, respectively, for 30 days prior and along with atrazine, could significantly ameliorate the oxidative stress, inflammation, and apoptosis induced by atrazine and regulated the hepatic cytochrome P450 activities. Furthermore, they improved liver function biomarkers and histopathology. In conclusion, our results revealed that zinc oxide nanoparticles and vitamin C supplementations could effectively protect against atrazine-induced hepatotoxicity.

Atrazine: cytotoxicity, oxidative stress, apoptosis, testicular effects and chemopreventive Interventions

“…Therefore, it is only at experimental doses, and not at relevant environmental concentrations has ATZ-induced hepatotoxicity been established for mammalian animals. However, one study (Jestadi et al, 2014), have demonstrated hepatotoxicity associated with elevated serum aspartate aminotransferase and alanine aminotransferase activity in animals exposed to ATZ at doses of 300 μg/kg b.w, which is more than 1,000 times lower than was used in the above studies (Campos-Pereira et al, 2012;Mohammed et al, 2023;Rashad et al, 2023). Thus, the proposal that ATZ effects, in mammalian animals may be influenced by differences in methodologies, sources and purity of chemical, solvents, and statistical analyses (Kligerman et al, 2000b), are important concepts to consider in studies focusing on ATZ-induced liver injury in animal models.…”

“…These biochemical alterations were found to induce inflammation associated with apoptosis through up-regulating Bax, nuclear factor-kappa B, TNF-α and minimising Bcl-2 gene expressions in the hepatic tissues. Light microscopy of liver sections was typified with vacuolated and degenerated hepatocytes surrounding dilated and congested blood sinusoids and central veins ( Mohammed et al, 2023 ). Additionally, the serum samples obtained from the animals were characterised with higher level of aspartate aminotransferase and alanine aminotransferase enzyme activity, and diminished albumin and globulins concentrations confirming liver toxicity.…”

“…Additionally, the serum samples obtained from the animals were characterised with higher level of aspartate aminotransferase and alanine aminotransferase enzyme activity, and diminished albumin and globulins concentrations confirming liver toxicity. Interestingly, zinc oxide nanoparticles (10 mg/kg b.w) or vitamin C (200 mg/kg b.w) pre-treatment through the oral route for 30 days could dampen the oxidative stress, inflammation, and apoptosis orchestrated by ATZ, suggesting that zinc oxide nanoparticles and vitamin C supplementations can effectively protect the liver from ATZ-hepatotoxicity ( Mohammed et al, 2023 ). Because, the dose 300 mg/kg b.w of ATZ is in the same range of doses as in other in vivo studies of ATZ model of experimental hepatotoxicity ( Santa Maria et al, 1987 ; Campos-Pereira et al, 2012 ; Rashad et al, 2023 ) or higher than those used in other ATZ mammalian models of experimental toxicology ( Liu et al, 2014 ; Liu et al, 2021 ; Khozimy et al, 2022 ), the hepatic injury observed in most of these studies above is of limited clinical relevance.…”