Thyme Oil and Thymol Counter Doxorubicin-Induced Hepatotoxicity via Modulation of Inflammation, Apoptosis, and Oxidative Stress

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.

Rutin and Quercetin Counter Doxorubicin-Induced Liver Toxicity in Wistar Rats via Their Modulatory Effects on Inflammation, Oxidative Stress, Apoptosis, and Nrf2

“…The present investigation found that DXR-injected animals exhibited elevated levels of serum total bilirubin, which is similar with the results of Liss et al [ 70 ], Ahmed [ 71 ], Hozayen et al [ 60 ], Hassan et al [ 67 ], Ahmed et al [ 68 ], and Ahmed et al [ 72 ]. These researchers argued that it is a clear indicator of liver disease and may be caused by bile ductile occlusion induced by portal triad inflammation and fibrosis and/or conjugated bilirubin reflux from necrotic hepatocytes to sinusoids.…”

“…The damaging effects of DXR on liver cells may attributed to the stimulation of oxidative stress and inflammation. Both increased levels of LPO and TNF-α have important implications of necrosis and damage of liver cells [67][68][69] (Scheme 2). The current investigation showed that employing rutin and quercetin for the treatment of DXRinjected rats remarkably decreased the raised activities of serum ALT, AST, and ALP and the level of total bilirubin as well.…”

Pinus mugo Essential Oil Impairs STAT3 Activation through Oxidative Stress and Induces Apoptosis in Prostate Cancer Cells

“…Specifically, several EOs and their components are reported to exert anti-proliferative effects and induce apoptosis in cancer cells with minimal effects on non-transformed ones [ 27 , 28 ]. Moreover, since some of them work synergistically with commonly used anticancer drugs, they have been proposed as adjuvants in chemotherapy [ 20 , 21 , 22 ].…”

“…They have been recognized as sources of many bioactive products that exhibit various biological and immunological activities, including anti-inflammatory, antibacterial, antibiofilm, antifungal and antiviral effects [ 16 , 17 , 18 , 19 ]. Furthermore, EOs have been shown to exert cancer cell targeting activity to increase the efficacy of commonly used chemotherapy drugs and to possess pro-immune functions [ 20 , 21 , 22 , 23 ]. Despite a large body of research indicating that EOs and their active compounds may have anticancer properties, not many successful drug formulations have reached the clinical stage.…”

Cinnamaldehyde Mitigates Atherosclerosis Induced by High-Fat Diet via Modulation of Hyperlipidemia, Oxidative Stress, and Inflammation

“…Zero (0) refers to the absence of lesion, “I” indicates a mild degree, “II” indicates a moderate degree, and “III” denotes a severe degree. The free software version of ImageJ (1.51d) was used for immunohistochemical examination and analysis of labeling [ 29 ]. Integrated intensities were evaluated using the ImageJ software (in pixels) for positive reactions with IL-1 β and TNF- α .…”