Preventive Effect of D-002, a Mixture of Long-Chain Alcohols from Beeswax, on the Liver Damage Induced with CCl₄ in Rats

Abstract

D-002 is a mixture of higher aliphatic primary alcohols purified from beeswax with antioxidant effects. Acute hepatotoxicity induced with CCl4 in rats has been related to increased hepatic lipid peroxidation and prevented with some antioxidants. This study investigated whether D-002 could prevent the acute CCl4-induced hepatotoxicity in rats. Animals were randomly distributed into four groups: a negative control treated orally with the vehicle and three groups injected with CCl4 (1 mL/kg) and treated orally either with the vehicle (positive control) or with D-002 (25 and 100 mg/kg). Eighteen hours after CCl4 dosing, rats were anesthetized, and livers were removed for histopathological studies. Some portions were taken and homogenized for assessing malondialdehyde (MDA) concentrations. Positive, but not negative, controls showed ballooned cells, swollen hepatocytes, and lipid-included hepatocytes, as well as necrotic areas and inflammatory infiltrates. D-002 (25 and 100 mg/kg) dose-dependently and significantly (P < .01) decreased the frequency of all abnormal liver cell types and increased that of normal hepatocytes compared with the positive controls, not showing necrotic areas or inflammatory infiltrates. D-002 dose-dependently decreased hepatic MDA levels, but only in the highest dose group were these levels significantly lower than in the positive control. In conclusion, D-002 effectively prevented the histological liver disturbances and lowered MDA levels, a marker of cellular lipid peroxidation, in rats treated with CCl4. Since increased liver lipid peroxidation has been postulated as a cause of CCl4-induced liver damage in rats, the preventive effects of D-002 could be due to its antioxidant action, but such a proposal still requires further research.

Mechanism of the Inhibitory Effects ofEucommia ulmoidesOliv. Cortex Extracts (EUCE) in the CCl4-Induced Acute Liver Lipid Accumulation in Rats

“…Thus, the biochemical mechanism underlying the development of CCl 4 steatosis/cirrhosis may involve MDA. In CCl 4 -treated rats, significantly increased levels of MDA have been shown [45]. …”

Effects of D-002, a mixture of high molecular weight beeswax alcohols, on patients with nonalcoholic fatty liver disease

“…Oral administration of D-002 has been shown to produce antioxidant effects in experimental [18-20] and clinical studies [21-23], and to exhibit hepatoprotective effects in experimental models of CCl4-induced liver injury [24]. …”

Effects of D-002, a mixture of beeswax alcohols, on osteoarthritis symptoms: a randomized placebo-controlled study

“…Oral treatment with D-002, however, is gastroprotective, rather than gastrotoxic, through a mechanism that involves increased secretion and improved composition of the gastric mucus, and reduced lipid peroxidation in the gastric mucosa [14][15][16]. Antioxidant effects of D-002 have been demonstrated in experimental and clinical studies [21][22][23][24][25][26][27]. Keeping in mind this background, we believed that D-002 could improve OA symptoms.…”