Polyethylene Terephthalate Nanoplastics Caused Hepatotoxicity in Mice Can be Prevented by Betaine: Molecular and Immunohistochemical Insights

ABSTRACT Polyethylene terephthalate nanoplastics (PET‐NPs) are one of the most frequently distributed nanoplastics in daily life. Betaine is thought to be a promising hepatoprotective agent. The current investigation focused on whether orally administered PET‐NPs caused hepatotoxicity and ameliorative effect of betaine. Forty adult male Swiss albino mice were randomly split into four groups: group I control, group II betaine (1000 mg/kg I/P), group III PET‐NPs (200 mg/kg orally), and group IV betaine plus PET‐NPs at doses similar to group II& III respectively. After 30 days, blood sample were collected then animals were euthanized and liver specimens were dissected out for biochemical and histopathological examination. PET‐NPs induced a significant elevation in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA), as well as an increase in the inflammatory genes a proto‐oncogene (c‐FOS) and cyclooxygenase 2 (COX2) (p ≤ 0.05), with a substantial decrease in glutathione (GSH) (p ≤ 0.05). Furthermore, on the level of histopathological analysis PET‐NPs caused alterations in hepatic tissue architecture as vascular dilatation and congestion with hepatocytes degeneration, bile duct epithelial hyperplasia and inflammatory cell infiltrations While on the level of immunohistochemistry, PET‐NPs trigger positive tumor necrosis factor‐alpha (TNF‐α) and nuclear factor‐kappa B (NF‐ҠB) expression in comparison to control. Meanwhile, betaine treatment reduced the deleterious effects of PET‐NPs. To summarize, PET‐NPs may cause hepatotoxicity in mice, with a belief that betaine could mitigate the detrimental impact. Mice exposed to PET‐NPs by oral administration & exposed to betaine through intraperitoneal injection. PET‐NPs trigger hepatotoxicity expressed by increasing MDA, COX2, c‐FOS and decrease GSH PET‐NPs cause inflammation confirmed by immunohistochemical analysis (TNF‐α & NF‐ҡB). Betaine cause hepatoprotection as antioxidant and anti‐inflammatory.