Protective effects of thymoquinone against cholestatic oxidative stress and hepatic damage after biliary obstruction in rats

Abstract

The aim of this study was to examine the preventive and therapeutic effects of thymoquinone (TQ) against cholestatic oxidative stress and liver damage in common bile duct ligated rats. A total of 24 male Sprague-Dawley rats were divided into three groups: control, bile duct ligation (BDL) and BDL + received TQ; each group contain 8 animals. The rats in TQ treated groups were given TQ (50 mg/kg body weight) once a day orally for 2 weeks starting 3 days prior to BDL operation. To date, no more biochemical and histopathological changes on common bile duct ligated rats by TQ treatment have been reported. The application of BDL clearly increased the tissue hydroxyproline (HP) content, malondialdehyde (MDA) levels and decreased the antioxidant enzyme [superoxide dismutase (SOD), glutathione peroxidase (GPx)] activities. TQ treatment significantly decreased the elevated tissue HP content, and MDA levels and raised the reduced of SOD, and GPx enzymes in the tissues. The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells, and neutrophil infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with TQ attenuated alterations in liver histology. The immunopositivity of alpha smooth muscle actin and proliferating cell nuclear antigen in BDL were observed to be reduced with the TQ treatment. The present study demonstrates that oral administration of TQ in bile duct ligated rats maintained antioxidant defenses and reduces liver oxidative damage and ductular proliferation. This effect of TQ may be useful in the preservation of liver function in cholestasis.

Thymoquinone Ameliorates Cadmium-Induced Nephrotoxicity, Apoptosis, and Oxidative Stress in Rats is Based on its Anti-Apoptotic and Anti-Oxidant Properties

“…The Cd-treated group was injected subcutaneously with CdCl2 dissolved in saline in the amount of 2 ml/kg/day for 30 days, resulting in a dosage of 1 mg/kg Cd [18]. The rats in the TQ-treated group were given TQ (50 mg/kg body weight) [13] once a day orally together with first Cd injection during the study period. At the end of the experiment, all rats were sacrificed by decapitation under ketamine-xylazine anesthesia.…”

“…There are several reports indicating that TQ has anti-oxidative, anti-inflammatory, anti-tumor, anti-ulcerogenic, chemopreventive, and hepatoprotective properties [10][11][12][13]. The previous studies demonstrated that TQ has a considerable protective effect against oxidative damage induced by a variety of free radical-generating agents, including nephrotoxicity produced by cisplatin [14], doxorubicin-induced nephropathy [15], carbon tetrachlorideevoked hepatotoxicity [16], and gastric mucosal injury induced by ischemia-reperfusion [17].…”

Enhancement of Bioavailability and Pharmacodynamic Effects of Thymoquinone Via Nanostructured Lipid Carrier (NLC) Formulation

“…Recently, several studies have shown that TQ has many pharmacological effects, including anti-oxidation and hepatoprotective effects against hepatotoxins (2,3), neuroprotective (4), anti-diabetic (5), anti-inflammatory (6), antimutagenic (7), and anti-carcinogenic (8). A recent study by Oguz et al shows that TQ inhibits common bile duct ligation (CBDL)-induced liver damage in rats including the fibrotic changes in the liver (9). So far, the hepatoprotective and antifibrotic effects of TQ is largely attributed to its anti-oxidant activity, which leads to decreased hepatocyte damage and thus decreased transactivation of hepatic stellate cells (HSCs).…”

Prophylactic effects of thymoquinone against carbon tetrachloride-induced hepatic damage in Sprague-Dawley rats

“…The seeds of N. sativa have long been used in traditional medicine for a wide range of illnesses, including headache, dysentery, infections, obesity, back pain, bronchial asthma, hypertension and gastrointestinal problems (Al-Rowais, 2002).TQ was shown to protect against hepatic damage (Mansour et al, 2001). For instance, Ogus et al, (2012) demonstrated that oral administration of TQ relieved bile duct proliferation, periductular fibrosis and hepatic damage in bile duct-ligated rats. Lebda et al, (2011) reported that TQ prevented liver enzyme leakage and lipid peroxidation induced by D-galactosamine in rats.…”

“…For instance, Ogus et al, (2012) demonstrated that oral administration of TQ relieved bile duct proliferation, periductular fibrosis and hepatic damage in bile duct-ligated rats. Lebda et al, (2011) reported that TQ prevented liver enzyme leakage and lipid peroxidation induced by D-galactosamine in rats. Nagi et al, (2010) observed that TQ protected mice against acetaminophen-induced hepatotoxicity.…”