1,8-Cineole Protects Against Liver Toxicity Induced by Aroclor-1254 in a Rat Model

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.