Abstract
Osteopenia or osteoporosis occurs frequently in alcoholics and patients with alcoholic fatty liver disease. Methoxsalen (MTS), 8-methoxypsoralen, improved osteoporosis in ovariectomized and diabetic mouse models; however, its effects on alcohol-induced osteopenia and steatosis have not been reported. This study examined the effects of MTS on alcohol-induced bone loss and steatosis. Rats in the alcohol groups were fed a Liber-DeCarli liquid diet containing 36% of its calories as alcohol. MTS was at 0.005% in their diet, while alendronate (positive control; 500 μg/kg BW/day) was administered orally for eight weeks. The pair-fed group received the same volume of isocaloric liquid diet containing dextrin-maltose instead of alcohol as the alcohol control group consumed the previous day. In the alcohol-fed rats, the MTS and alendronate increased the bone volume density, bone surface density and trabecular number, while the bone specific surface, trabecular separation and structure model index were decreased in the tibia. MTS down-regulated tibial tartrate-resistant acid phosphatase 5 (TRAP) expression compared to the alcohol control group. MTS or alendronate prevented chronic alcohol-induced hepatic lipid accumulation and the triglyceride level in the alcohol-fed rats by decreasing the lipogenic enzyme activities and increasing the fatty acid oxidation enzyme activities. MTS reduced significantly the serum levels of alcohol, TRAP and tumor necrosis factor-α compared to the alcohol control group. Overall, these results suggest that MTS is likely to be an alternative agent for alcoholic osteopenia and hepatosteatosis.
Highlights
Chronic alcohol consumption-related diseases, including fatty liver disease, hepatitis, fibrosis and cirrhosis, are the leading causes of death for alcoholics [1]
Osteoporosis or osteopenia is a common complication of chronic liver disease, which is associated with age, BMI and alcohol liver disease [3]
Two-dimensional images of the distal femur and tibia showed that eight-week alcohol (36% of total energy) feeding induced bone-loss (Figure 1A,B), but MTS and AD reversed it, which was more effective on the tibia than the femur (Figure 1)
Summary
Chronic alcohol consumption-related diseases, including fatty liver disease, hepatitis, fibrosis and cirrhosis, are the leading causes of death for alcoholics [1]. Many studies have demonstrated that chronic and heavy alcohol intake is associated with impaired balanced bone remodeling and an increased risk of bone fragility [2]. Osteoporosis or osteopenia is a common complication of chronic liver disease, which is associated with age, BMI and alcohol liver disease [3]. Previous studies reported that patients with alcoholic liver diseases are more likely to have osteoporosis or osteopenia than those with chronic viral hepatitis [3,4]. Bisphosphonates and vitamin D supplementation have been used to prevent bone destruction and bone toxicity related to alcohol abuse in mice [5]. Many studies have examined natural plants and their bioactive compounds for preventing bone loss in the laboratory and in clinics [6,7]
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