TY - JOUR
T1 - Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis
AU - Kumar, Virender
AU - Xin, Xiaofei
AU - Ma, Jingyi
AU - Tan, Chalet
AU - Osna, Natalia
AU - Mahato, Ram I.
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/9
Y1 - 2021/9
N2 - Type 2 diabetes mellitus (T2DM) associated non-alcoholic fatty liver disease (NAFLD) is the fourth-leading cause of death. Hyperglycemia induces various complications, including nephropathy, cirrhosis and eventually hepatocellular carcinoma (HCC). There are several etiological factors leading to liver disease development, which involve insulin resistance and oxidative stress. Free fatty acid (FFA) accumulation in the liver exerts oxidative and endoplasmic reticulum (ER) stresses. Hepatocyte injury induces release of inflammatory cytokines from Kupffer cells (KCs), which are responsible for activating hepatic stellate cells (HSCs). In this review, we will discuss various molecular targets for treating chronic liver diseases, including homeostasis of FFA, lipid metabolism, and decrease in hepatocyte apoptosis, role of growth factors, and regulation of epithelial-to-mesenchymal transition (EMT) and HSC activation. This review will also critically assess different strategies to enhance drug delivery to different cell types. Targeting nanocarriers to specific liver cell types have the potential to increase efficacy and suppress off-target effects.
AB - Type 2 diabetes mellitus (T2DM) associated non-alcoholic fatty liver disease (NAFLD) is the fourth-leading cause of death. Hyperglycemia induces various complications, including nephropathy, cirrhosis and eventually hepatocellular carcinoma (HCC). There are several etiological factors leading to liver disease development, which involve insulin resistance and oxidative stress. Free fatty acid (FFA) accumulation in the liver exerts oxidative and endoplasmic reticulum (ER) stresses. Hepatocyte injury induces release of inflammatory cytokines from Kupffer cells (KCs), which are responsible for activating hepatic stellate cells (HSCs). In this review, we will discuss various molecular targets for treating chronic liver diseases, including homeostasis of FFA, lipid metabolism, and decrease in hepatocyte apoptosis, role of growth factors, and regulation of epithelial-to-mesenchymal transition (EMT) and HSC activation. This review will also critically assess different strategies to enhance drug delivery to different cell types. Targeting nanocarriers to specific liver cell types have the potential to increase efficacy and suppress off-target effects.
KW - Cirrhosis
KW - Diabetes
KW - Hepatocellular carcinoma
KW - Inflammation
KW - Liver fibrosis
KW - NAFLD
UR - http://www.scopus.com/inward/record.url?scp=85111807399&partnerID=8YFLogxK
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U2 - 10.1016/j.addr.2021.113888
DO - 10.1016/j.addr.2021.113888
M3 - Review article
C2 - 34314787
AN - SCOPUS:85111807399
SN - 0169-409X
VL - 176
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
M1 - 113888
ER -