LAUSR

This study aimed to demonstrate the protective effect of 1,8‐cineole against Aroclor 1254 (A1254)‐induced liver toxicity in male rats and to elucidate the underlying mechanisms. A1254 is among the persistent organic pollutants and is a toxic substance that can cause serious damage to various organs such as the liver, brain, and lungs. 1,8‐cineole, a monoterpene, possesses significant pharmacological activities such as antioxidant, anti‐inflammatory, and anticancer effects. Thirty‐two healthy young (4−6 weeks) male Wistar albino rats (200–300 g) were used. The animals were randomly divided into four equal groups: Control, Aroclor, Cineole, and Aroclor+Cineole (n = 8). Rats were daily administered A1254 (1 mg/kg, intraperitoneally) either alone or in combination with 1,8‐cineole (100 mg/kg orally in corn oil) for 30 days. The liver tissues and serum were collected from the rats under anesthesia. The protective effect of 1,8‐cineole against A1254‐induced liver damage was demonstrated using ELISA, RT‐PCR, histopathological analysis, and immunohistochemical evaluation methods. A1254 administration increased the total oxidant status (TOS) level and triggered oxidative stress by decreasing the total antioxidant status (TAS). However, 1,8‐cineole significantly reduced TOS levels and increased TAS levels in serum and liver tissues (p < 0.05). A1254 increased the pro‐apoptotic Bax gene expression in liver tissues, while 1,8‐cineole significantly decreased (p < 0.05). Similarly, A1254 increased the gene expressions of pro‐inflammatory cytokines tumor necrosis factor alpha (TNF‐α), interleukin‐1‐beta (IL‐1β), inducible nitric oxide synthase (iNOS), and interferon‐gamma (INF‐γ) in liver tissues, whereas 1,8‐cineole decreased the expression of these genes (p < 0.05). Moreover, 1,8‐cineole reduced the histopathological changes associated with A1254‐induced oxidative stress and inflammation in liver tissues. In conclusion, 1,8‐cineole may be a protective agent due to its anti‐apoptotic effect, reduction of oxidative damage, anti‐inflammatory efficacy, and amelioration of histopathological changes in liver toxicity.