Geraniol prevents CCl4-induced hepatotoxicity via suppression of hepatic oxidative stress, pro-inflammation and apoptosis in rats

Document Type

Article

Publication Title

Toxicology Reports

Abstract

Carbon tetrachloride (CCl4) is a classic chemical hepatotoxicant that triggers liver damage through hepatic exacerbation of oxidative stress. Geraniol (GRL) is a natural bioactive acyclic monoterpene with several pharmacological effects. We thus explored whether GRL could prevent CCl4-triggered hepatic toxicity. Rats were divided and administered GRL (100 mg/kg) and/or CCl4 (1 ml/kg of 1:1 v/v CCl4: olive oil) in Control group, GRL group, CCl4 group, GRL + CCl4 groups 2 times per week for 4 consecutive weeks. CCl4 caused significantly (p < 0.05) elevated serum activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TB), whereas the albumin (ALB) and total protein (TP) levels were significantly (p < 0.05) reduced relative to the control group. The liver activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) decreased significantly (p < 0.05), while malondialdehyde (MDA) level evidently elevated in comparison to the control group. The CCl4 exposure caused significant increases in proinflammatory interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), apoptotic caspase-3 and caspase-9 levels, whereas the anti-inflammatory interleukin-4 (IL-4) and interleukin-10 (IL-10) were reduced in consistent with histopathological changes compared to the control. On the contrary, the GRL administration prevented the hepatic toxicity and lesions through restoration of liver status markers, antioxidant enzyme activities, MDA, cytokines and apoptosis in comparison to the CCl4 group. Altogether, the findings reveal that GRL could abrogate CCl4-provoked hepatic toxicity via inhibition of hepatic oxidative stress, inflammation and apoptosis in rats.

First Page

128

Last Page

134

DOI

10.1016/j.toxrep.2024.01.007

Publication Date

6-1-2024

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