The Aqueous Extract of Artemisia Absinthium L. Stimulates HO-1/MT-1/Cyp450 Signaling Pathway Via Oxidative Stress Regulation Induced by Aluminium Oxide Nanoparticles (α and Γ) Animal Model.

Background This research aimed to evaluate the protective effects of Artemisia Absinthium L. (Abs) against liver damage induced by aluminium oxide nanoparticles (Al2O3 NPs) in rats, including both structural and functional changes associated with hepatotoxicity. Methods Thirty-six rats were randomly divided into six groups (n = 6). The first group received no treatment. The second group was orally administered Abs at a dose of 200 mg/kg/b.w. The third and fifth groups were injected intraperitoneally with gamma-Al2O3 NPs and alpha-Al2O3 NPs, respectively, at a dose of 30 mg/kg/b.w. The fourth and sixth groups were pre-treated with oral Abs at a dose of 200 mg/kg/b.w. along with intraperitoneal injection of gamma-Al2O3 NPs and alpha-Al2O3 NPs, respectively, at a dose of 30 mg/kg/b.w. Results Treatment with gamma-Al2O3 NPs resulted in a significant decrease (P < 0.05) in total body weight gain, relative liver weight to body weight, and liver weight in rats. However, co-administration of gamma-Al2O3 NPs with Abs significantly increased body weight gain (P < 0.05). Rats treated with Al2O3 NPs (gamma and alpha) exhibited elevated levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), alanine transaminase (ALT), and aspartate aminotransferase (AST). Conversely, treatment significantly reduced glutathione peroxidase (GPx), catalase (CAT), total superoxide dismutase (T-SOD), and total antioxidant capacity ( TAC) levels compared to the control group. Furthermore, the expression of heme oxygenase-1 (HO-1) and metallothionein-1 (MT-1) mRNAs, cytochrome P450 (CYP P450) protein, and histopathological changes were significantly up-regulated in rats injected with Al2O3 NPs. Pre-treatment with Abs significantly reduced MDA, AST, HO-1, and CYP P450 levels in the liver, while increasing GPx and T-SOD levels compared to rats treated with Al2O3 NPs. Conclusion The results indicate that Abs has potential protective effects against oxidative stress, up-regulation of oxidative-related genes and proteins, and histopathological alterations induced by Al2O3 NPs. Notably, gamma-Al2O3 NPs exhibited greater hepatotoxicity than alpha-Al2O3 NPs.