Abstract
Doxorubicin (DOX) is an effective anticancer agent with a wide spectrum of activities. However, it has many adverse effects on various organs especially on the liver. Thymol, one of the major components of thyme oil, has biological properties that include anti-inflammatory and antioxidant activities. Thus, this study was designed to examine thyme oil and thymol for their ability to prevent doxorubicin-induced hepatotoxicity in Wistar rats. Hepatotoxicity was induced by an intraperitoneal injection of doxorubicin, at a dose of 2 mg/kg bw/week, for seven weeks. Doxorubicin-injected rats were supplemented with thyme oil and thymol at doses 250 and 100 mg/kg bw, respectively, four times/week by oral gavage for the same period. Treatment of rats with thyme oil and thymol reversed the high serum activities of AST, ALT, and ALP and total bilirubin, AFP, and CA19.9 levels, caused by doxorubicin. Thyme oil and thymol also reduced the high levels of TNF-α and the decreased levels of both albumin and IL-4. These agents ameliorated doxorubicin-induced elevation in hepatic lipid peroxidation and associated reduction in GSH content and GST and GPx activities. Further, the supplementation with thyme oil and thymol significantly augmented mRNA expression of the level of antiapoptotic protein Bcl-2 and significantly downregulated nuclear and cytoplasmic levels of the hepatic apoptotic mediator p53. Thus, thyme oil and thymol successfully counteracted doxorubicin-induced experimental hepatotoxicity via their anti-inflammatory, antioxidant, and antiapoptotic properties.
Highlights
The liver is a central organ in the human body, coordinating several key metabolic roles
In conductance with the previous publications, the current study investigated the preventive impact of thyme oil and its major constituent, thymol, on liver injury, oxidative stress, inflammatory status, and apoptosis in DOX-intoxicated rats
The current study shows the impact of DOX-induced hepatotoxicity manifested by a significant elevation in serum ALT, AST, and alkaline phosphatase (ALP) activities and total bilirubin level, as well as a significant decrease in serum albumin
Summary
The liver is a central organ in the human body, coordinating several key metabolic roles. Due to its unique position in the human body, the liver is exposed to a vast array of agents including alcohol and drugs, as well as pathogens that may able to impair its function [1]. The liver is intimately connected to inflammation for responding to harmful stimuli. Sustained liver inflammation can induce liver fibrosis and cirrhosis or hepatocellular carcinoma (HCC). Inflammation and liver cancer may be linked through the inflammation-fibrosis-cancer axis [2]. HCC is common cause mortality worldwide [3, 4]. Chemotherapy is a key treatment for later stages to prevent recurrence after surgery [5]
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