Combined use of ginger and atorvastatin.
Herb-drug interactions (Research)
|Publication:||Name: Australian Journal of Medical Herbalism Publisher: National Herbalists Association of Australia Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2011 National Herbalists Association of Australia ISSN: 1033-8330|
|Issue:||Date: Spring, 2011 Source Volume: 23 Source Issue: 1|
|Topic:||Event Code: 310 Science & research|
|Geographic:||Geographic Scope: Australia Geographic Code: 8AUST Australia|
Heeba G, Abd-Elghany M. 2011. Effect of combined administration of
ginger (Zingiber officinale Roscoe) and atorvastatin on the liver of
rats. Phytomed 17:14;1076-81.
Statins (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitors) are a group of drugs used in the treatment of hyperlipidemia. Atorvastatin (AT) differs from other statins in that it has a longer action and presents active metabolites which are biotransformed mainly by cytochrome P3A4 in the liver. These have been linked to hepatotoxicity and liver injury.
Zingiber officinale, ginger, is a commonly used culinary and medicinal spice that contains active phenolic compounds with antioxidant, anticancer, anti-inflammatory and antithrombotic properties. Previous studies have shown that ginger significantly reduces plasma cholesterol level exhibiting hypoglycemic, hypolipidemic and antia-therosclerotic effects. The aim of this animal study was to evaluate the possible protective role of ginger with low and high doses of atorvastatin induced hepatic injury, with particular attention to the hypolipidemic and the hepatoprotective properties of this spice.
An aqueous ethanol extract of ginger was prepared using 50% ethanol, pre solubilised in saline for the in vivo studies. Male Wistar rats were divided into eight groups: 1 treated with saline and kept as control; 2 treated with ginger (400 mg/kg/day orally); 3 treated with AT (20 mg/kg/day orally); 4 treated with AT (20 mg/kg/day orally) and ginger (400 mg/kg orally); 5 treated with AT (20 mg/kg/day orally) and vitamin E (200 mg/kg orally); 6. treated with AT (80 mg/kg/day orally); 7 treated with AT (80 mg/kg/day orally) and ginger (400 mg/kg orally); and 8 treated with AT (80 mg/kg/day) and vitamin E (200 mg/kg orally).
Following four weeks of treatment the rats were sacrificed under ether anesthesia. The blood was collected by cardiac puncture, allowed to clot for 30 min and centrifuged at 1000xg for 15-20 min to separate sera. Livers were excised and homogenised in phosphate buffer saline (0.1 M, pH 7.4). Serum total cholesterol, triglycerides, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined. Liver homogenates were used for the estimation of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) enzymes activities. The total nitrites/nitrates in liver homogenate were also assayed. Liver sections were also examined for pathological findings of hepatic changes.
There was a significant reduction of total cholesterol levels in rats treated with ginger or AT (20 and 80 mg/kg) compared with control (P <0.05). There was no significant reduction in triglycerides. Concurrent administration of AT with ginger or vitamin E also significantly reduced cholesterol compared with control (P <0.05) but only at the lower dose of AT. In the AT treated groups the serum levels of ALT and AST were markedly raised compared with control group. Simultaneous administration of ginger with AT (20 and 80 mg/kg) reduced the serum levels of ALT and AST compared with AT only groups. The change was less noticeable with vitamin E.
Administration of ginger produced significant decrease in MDA level and appreciable increase in hepatic SOD and CAT activities (P < 0.05). Compared with control AT (20 and 80 mg/kg) exerted a significant elevation in hepatic NO level whereas simultaneous administration of AT (20 and 80 mg/kg) and ginger or vitamin E markedly reduced NO production compared with AT-only groups.
Histopathological examination of liver sections of the control and ginger treated rats showed normal lobular architecture and normal hepatic cells. Consistent with serum ALT and AST levels, histopathological examination of livers of AT (80 mg/kg) treated rats showed distorted architecture with centrilobular necrosis and various degenerative changes in hepatic cells. Concurrent treatment with AT (20 and 80 mg/ kg) and ginger or vitamin E significantly attenuated the extent and severity of the histological features of liver damage induced by AT alone. Most HMG-CoA reductase inhibitors are metabolised by the liver, statin often leading to increased liver enzymes. This study verified the hepatotoxicity of high dose AT (80 mg/kg) indicated by the increased serum ALT and AST levels more than three times the normal control.
The study results demonstrated that combination of ginger and AT significantly reduced AT induced hepatic changes. The effect of ginger was comparable to that of a standard antioxidant vitamin E, indicating that the antioxidant effect of ginger plays an important role in the attenuation of hepatic injury. The combination with ginger also enhanced total cholesterol lowering efficacy of AT as compared with therapy using AT alone. A significant reduction in cholesterol levels was observed in the rats given ginger only.
The researchers concluded that ginger can enhance the hypocholesterolemic effects of AT, lowering cholesterol levels and decreasing the likelihood of subsequent hepatic changes. This they suggest argues the case of a synergistic combination therapy.
Tessa Finney-Brown mnhaa
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