The Hepatotoxicity of Nigella sativa Oil Linked to the Route of Administration

Background: Even Nigella sativa oil (NSO) has several pharmacological effects; the route of administration is critical to obtain the desired activity in which intraperitoneal injection (IP) of oil recruits macrophages and induces inflammation. Objective: The current study aimed to determine the best administration route of NSO in rats either oral or IP. Methods: The components of NSO, routine blood analyses, hepatic oxidative stress and pro-inflammatory parameters, and liver histopathological study were evaluated. Results: NSO contained 32.14% E,E,Z- 1, 3, 12- nonadecatriene- 5, 14 diol, 25% thymoquinone (TQ) and 3.74% dimethyl sulfoxide (DMSO). In addition, the rats who received IP injection of NSO showed an increase in hepatic enzymes, lipid profiles, oxidative stress, and inflammatory markers. This was associated with hepatic up-regulation of the A disintegrin and metalloproteinase 17 (ADAM-17) genes, which are corroborated by a reduction in hepatic tissue inhibitor of metalloproteinase 3 (TIMP-3) concentration. These indications were seen in rats given a small amount of DMSO (NSO vehicle), indicating that NSO-oral delivery was safer than IP. Conclusion: NSO-IP administration promotes the hepatic oxidative stress-inflammation axis; thus, NSO is a generally safe chemical, especially when administered orally to experimental animals.