Insight into the hepatoprotective, hypolipidemic, and antidiabetic impacts of aliskiren in streptozotocin-induced diabetic liver disease in mice

Abstract

Background Diabetic hepatopathy is a serious complication of poorly controlled diabetes mellitus. An efficient antidiabetic drug which keeps normal liver tissues is not available. The renin-angiotensin system has been reported to be involved in both diabetic state and liver function. Aliskiren is a direct renin inhibitor and a recently antihypertensive drug with poly-pharmacological properties. The aim of the current study is to explore the possible hepatoprotective effects and mechanisms of action of aliskiren against streptozotocin (STZ) induced liver toxicity. Methods Mice were distributed to 3 groups; first: the normal control group, second: the diabetic control group, third: the diabetic group which received aliskiren (25 mg/kg; oral) for 4 weeks. At the end of the treatment period, plasma glucose, insulin, lipid profile, oxidative stress, and liver function tests were evaluated spectrophotometrically. ELISA technique was used to measure the expression levels of TNF-α and adiponectin. Furthermore, a Histopathological examination of liver samples was done. Results It was shown that aliskiren treatment ameliorated the STZ-induced oxidative stress and elevated inflammatory biomarkers, hypercholesterolemia, serum aminotransferases and alkaline phosphatase levels in diabetic mice. In addition, hepatocellular necrosis, and fibrosis were improved by aliskiren treatment. Conclusion aliskiren protects against the liver damage caused by STZ-induced diabetes. This can be explained by its ability to block angiotensin-II, and its anti-diabetic, hypocholesterolemic, antioxidant and anti-inflammatory effects. Aliskiren could be a novel therapeutic strategy to prevent liver diseases associated with hypertension and diabetes mellitus. Graphical Abstract

Pichia pastoris Mediated Digestion of Water-Soluble Polysaccharides from Cress Seed Mucilage Produces Potent Antidiabetic Oligosaccharides

“…STZ treatment caused significant damage to the liver by altering hepatocyte structures, causing hepatomegaly, dilation of hepatic sinusoid capillaries, apoptosis, increased adipogenesis and cell death in hepatocytes. Besides, STZ treatments also induced signs of inflammation in the liver, which needed to be reversed or stabilized in order to combat diabetes [ 60 ].…”

Unsupervised cluster analysis of clinical and metabolite characteristics in patients with chronic complications of T2DM: an observational study of real data

“…Cornelia G Bala et al found that the disruption of the tyrosine biosynthesis pathway might be disrupted related to the high oxidative stress response in patients with type 2 diabetes (38). Oxidative stress is a key pathogenic factor in diabetic complications and can lead to the development of microangiopathy and ASCVD (39,40). Changes in metabolite levels may reflect the occurrence of multiple pathogenic mechanisms.…”

Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing

“…In the field of amide synthesis, since α -substituted aliphatic chiral amides are common substructures across bioactive compounds like Aliskiren 340 , 341 , 342 , 343 and Cebulactam A 344 , 345 , 346 , efficient α -enantiopure amides synthesis methods and late-stage application require further development.…”