2-[(4-Chlorobenzyl) amino]-4-methyl-1,3-thiazole-5-carboxylic acid exhibits antidiabetic potential and raises insulin sensitivity via amelioration of oxidative enzymes and inflammatory cytokines in streptozotocin-induced diabetic rats

Biomed Pharmacother. 2017 May;89:651-659. doi: 10.1016/j.biopha.2017.02.043. Epub 2017 Mar 3.

Abstract

Thiazole derivatives are potential candidates for drug development. They can be efficiently synthesized and are extremely active against several diseases, including diabetes. In our present study, we investigated the anti-diabetic, anti-oxidant and anti-inflammatory properties of 2-[(4-Chlorobenzyl) amino]-4-methyl-1,3-thiazole-5-carboxylic acid (BAC) a new thiazole derivative, in a streptozotocin (STZ) induced neonatal model of non-insulin dependent diabetes mellitus (NIDDM) rats. Diabetes was induced by injecting STZ (100mg/kg) intraperitoneally to two days old pups. BAC administration for 3 weeks significantly decreased blood glucose and raised insulin level and improves insulin sensitivity (KITT) level. Additionally, BAC also suppressed several inflammatory cytokines generation as evidenced by decreased levels of serum tumor necrosis factor-α and interleukin-6. In addition, BAC also protects against hyperlipidemia and liver injury. Furthermore, BAC significantly restored pancreatic lipid peroxidation, catalase, superoxide dismutase, and reduced glutathione content. Histological studies of pancreatic tissues showed normal architecture after BAC administration to diabetic rats. Altogether, our results suggest that BAC successfully reduces the blood glucose level and possesses anti-oxidant as well as anti-inflammatory activity. This leads to decreased histological damage in diabetic pancreatic tissues suggesting the possibility of future diabetes treatments.

Keywords: Hyperinsulinemia; Inflammatory cytokines; Insulin resistance; NIDDM; Oxidative stress; Streptozotocin.

MeSH terms

  • Animals
  • Animals, Newborn
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Cytokines / antagonists & inhibitors*
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / enzymology
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Glucose Tolerance Test
  • Glycated Hemoglobin / analysis
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / pharmacology*
  • Insulin Resistance*
  • Lipid Metabolism / drug effects
  • Oxidative Stress / drug effects*
  • Pancreas / pathology
  • Rats
  • Rats, Wistar
  • Thiazoles / chemical synthesis
  • Thiazoles / pharmacology*

Substances

  • 2-((4-chlorobenzyl)amino)4-methyl-1,3-thiazole-5-carboxylic acid
  • Blood Glucose
  • Cytokines
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Thiazoles