Chondroitin sulfate (CS) has antioxidative, anti-inflammatory, anti-osteoarthritic and hypoglycemic effects. However, whether it has antidiabetic osteoporosis effects has not been reported. Therefore, in this study, we established a STZ-induced diabetic rat model; CS (500 mg kg−1 d−1) was orally administrated for eight weeks to study its preventive effects on diabetic osteoporosis. The results showed that eight weeks of CS treatment improved the symptoms of diabetes; the CS-treated group has increased body weight, decreased water or food intake, decreased blood glucose, increased bone-mineral density, repaired bone morphology and decreased femoral osteoclasts and tibia adipocytes numbers. After CS treatment, bone histomorphometric parameters returned to normal, the levels of serum inflammatory cytokines (IL-1β, IL-6 and TNF-α) decreased significantly, serum SOD, GPX and CAT activities increased and MDA level increased. In the CS-treated group, the levels of serum ALP, CTX-1, TRACP 5b, osteocalcin and RANKL decreased and the serum RUNX 2 and OPG levels increased. Bone immunohistochemistry results showed that CS can effectively increase the expression of OPG and RUNX2 and reduce the expression of RANKL in diabetic rats. All of these indicate that CS could prevent STZ induced diabetic osteoporosis—mainly through decreasing blood glucose, antioxidative stress, anti-inflammation and regulation of OPG/RANKL expression. CS can therefore effectively prevent bone loss caused by diabetes.
Estrogens are steroid hormones with a wide range of biological activities. The excess of estrogens can lead to decreased bile flow, toxic bile acid (BA) accumulation, subsequently causing intrahepatic cholestasis. Estrogen-induced cholestasis (EIC) may have increased incidence during pregnancy, and within women taking oral contraception and postmenopausal hormone replacement therapy, and result in liver injury, preterm birth, meconium-stained amniotic fluid, and intrauterine fetal death in pregnant women. The main pathogenic mechanisms of EIC may include deregulation of BA synthetic or metabolic enzymes, and BA transporters. In addition, impaired cell membrane fluidity, inflammatory responses and change of hepatocyte tight junctions are also involved in the pathogenesis of EIC. In this article, we review the role of estrogens in intrahepatic cholestasis, and outlined the mechanisms of EIC, providing a greater understanding of this disease.
Intrahepatic cholestasis (IC) is a liver disease caused by disorders in bile formation and excretion, owing to structural and functional abnormalities in hepatocytes and/or bile capillaries. IC is commonly caused by hepatitis virus, alcohol consumption, drug-induced liver damage, autoimmune liver disease and heredity. In the absence of effective treatment, IC can progress to liver fibrosis, cirrhosis and ultimately liver failure. However, the mechanisms underlying IC remain poorly understood. IC is believed to be closely associated with changes in the transcription, function and localization of hepatocellular transport proteins. To better understand the molecular mechanisms of transport proteins in IC, herein, we review the roles of these transport proteins and discuss their underlying regulatory mechanisms in IC. Our aim is to provide a reference for understanding IC pathogenesis and developing effective drug therapies.
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