Curcumin protects rat liver from streptozotocin-induced diabetic pathophysiology by counteracting reactive oxygen species and inhibiting the activation of p53 and MAPKs mediated stress response pathways

Abstract

Curcumin (CUR) is a highly pleiotropic molecule and possesses anti-inflammatory, hypoglycemic, antioxidative, wound-healing and antimicrobial activities. The present study was carried out to investigate whether CUR plays any beneficial role in streptozotocin (STZ) induced hepatic pathophysiology in diabetic rats. STZ exposure increased hepatic damage associated serum markers (ALT, ALP and LDH) as well as NO production in the liver tissue. Moreover, the same exposure enhanced ROS generation and lipid peroxidation; reduced GSH levels and antioxidant enzyme activities. Hyperglycemia induced hepatic pathophysiology also activated stress response pathways (involving phosphorylation of p38, ERK1/2 MAPKs and p53) and reduced mitochondrial membrane potential which in turn led to cellular apoptosis as evidenced from increased hepatic DNA fragmentation as well as FACS analysis. However, treatment with CUR effectively counteracts diabetes-induced, oxidative stress mediated hepatic damage and could act as a therapeutic in lessening liver dysfunction in diabetic subjects.

Atorvastatin induced hepatic oxidative stress and apoptotic damage via MAPKs, mitochondria, calpain and caspase12 dependent pathways

“…They play important roles in intracellular transcriptional and posttranslational responses. ROS production causes sustained MAPKs activation which has been studied intensively as a possible mechanism for cell proliferation, differentiation, survival and apoptosis (Pearson et al, 2001;Festa et al, 2011;Ghosh et al, 2015). Our present data demonstrated that ROS may serve as a link between mitochondrial dysfunction and MAPKs.…”

Shorea roxburghii Leaf Extract Ameliorates Hyperglycemia Induced Abnormalities in High Fat/Fructose and Streptozotocin Induced Diabetic Rats

“…The secretion of abnormal levels of liver function enzymes in the blood are vital indicators of liver injury in DM. ALT, AST and ALP levels have been shown to be increased in hepatic insulin resistance and T2DM . In this study, SRL significantly reduced the level of these biomarkers of liver injury in the treated diabetic rats.…”

“…ALT, AST and ALP levels have been shown to be increased in hepatic insulin resistance and T2DM. [28,29] In this study, SRL significantly reduced the level of these biomarkers of liver injury in the treated diabetic rats.…”

Curcumin improves the effect of a reduced insulin dose on glycemic control and oxidative stress in streptozotocin‐diabetic rats

“…The antidiabetic activity of curcumin has been well documented in both type 1 (Gutierres et al, ) and type 2 (Shao et al, ) DM models, improving not only the levels of glycemia but also those of dyslipidemia and tissue damage markers. Previous studies carried out by groups from our laboratory (Arcaro et al, ; Assis et al, ) and by others (Ghosh, Bhattacharyya, Rashid, & Sil, ) have found that the treatment of diabetic rats with curcumin is able to reduce in vivo oxidative stress. These findings identify curcumin as a promising adjunct to insulin therapy for diabetes.…”