Protective Effects of Methoxsalen Supplementation on Chronic Alcohol-induced Osteopenia and Steatosis in Rats

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.

Xanthotoxin (8‐methoxypsoralen): A review of its chemistry, pharmacology, pharmacokinetics, and toxicity

“…XAT can inhibit the production of the chondrocyte hypertrophy marker Runt related transcription factor 2 (RUNX2) (Cao et al, 2017), matrix metalloproteinase 13, via the P38-mitogen-activated protein kinase (P38-MAPK/HDAC4) pathway, while further studies showed that XAT decreased the activation of P38 mitogen-activated protease, which in turn increased the expression of histone deacetylated protease 4, thereby inhibiting the production of RUNX2. In an ethanol-induced osteoporosis model (Ham, Choi, Lee, & Lee, 2020), they found that 8-MOP increased serum estradiol, osteocalcin levels and bone alkaline phosphatase activity,…”

“…XAT can inhibit the production of the chondrocyte hypertrophy marker Runt related transcription factor 2 (RUNX2) (Cao et al, 2017), matrix metalloproteinase 13, via the P38‐mitogen‐activated protein kinase (P38‐MAPK/HDAC4) pathway, while further studies showed that XAT decreased the activation of P38 mitogen‐activated protease, which in turn increased the expression of histone deacetylated protease 4, thereby inhibiting the production of RUNX2. In an ethanol‐induced osteoporosis model (Ham, Choi, Lee, & Lee, 2020), they found that 8‐MOP increased serum estradiol, osteocalcin levels and bone alkaline phosphatase activity, and down regulated Receptor activator of nuclear factor‐κB ligand (RANKL), also inhibit the activation of PI3K/AKT, JNK/MAPK, and NF‐κB signaling pathways, thereby enhancing osteoblast differentiation and thus protecting bone structure. Nuclear factor of activated T cells c1 (NFATC1) and TRAP expression to reduce the number of osteoclasts in patients' tissues (Ham, Choi, Lee, & Lee, 2019).…”

plantMASST - Community-driven chemotaxonomic digitization of plants

“…It is a major component of the macular pigment in the human retina and is believed to help protect the eyes from oxidative damage and age-related macular degeneration 48 . Methoxsalen is a naturally occurring compound found in certain plants, including citrus fruits like oranges and lemons, as well as in various plants such as figs and parsley 49 . Methoxsalen is primarily used in a medical procedure known as PUVA (psoralen plus ultraviolet A) therapy, and it is also used to treat skin conditions like psoriasis, vitiligo, and eczema 50 .…”

Pengaruh Pemberian Alkohol Terhadap Sistem Rangka

“…Alkohol merupakan salah satu zat teratogen yang dapat menyebabkan gangguanpada kehamilan Konsumsi alkohol mengakibatkan berbagai efek berbahaya terhadap kesehatan, seperti kerusakan hati, gangguan kognitif, dan gangguan perkembangan embrio (Zakaria et al, 2017). Selain itu, penyakit yang berhubungan dengan konsumsi alkohol kronis diantaranya fatty liver disease, hepatitis, fibrosis, dan sirosis hepar, merupakan penyebab utama kematian bagi pecandu alkohol (Ham et al, 2020). Apabila mengonsumsi alkohol selama kehamilan, dapat menyebabkan kelainan otak dan wajah, keterlambatan pertumbuhan dan kognitif, serta komplikasi neurologis dan perilaku.…”

“…Beberapa penelitian menunjukkan bahwa asupan alkohol yang berlebihan dan berat dikaitkan dengan perubahan bentuk tulang dan peningkatan risiko kerapuhan tulang, meskipun pengaruh alkohol pada pengeroposan tulang masih kontrovesial (Ham et al, 2020). Namun penelitian lain menunjukkan bahwa konsumsi alkohol secara kronis dapat mengganggu metabolisme tulang dan menyebabkan osteoporosis dengan cara menghambat sel-sel osteoblas (Rosa et al, 2019).…”