title: 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.
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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Yam Nath
authors.initials: YN
authors.lastname: Paudel
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Md Rahmat
authors.initials: MR
authors.lastname: Ali
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Sadia
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Adil
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India; School of Allied Health Sciences, Sharda University, Greater Noida, Uttar Pradesh, India.
authors.forename: Md Sayeed
authors.initials: MS
authors.lastname: Akhtar
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Ravisha
authors.initials: R
authors.lastname: Wadhwa
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Bawa
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India. Electronic address: msharma@jamiahamdard.ac.in.
authors.forename: Manju
authors.initials: M
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010179:Pancreas / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D013844:Thiazoles; C000626251:2-((4-chlorobenzyl)amino)4-methyl-1,3-thiazole-5-carboxylic acid
keywords: Hyperinsulinemia; Inflammatory cytokines; Insulin resistance; NIDDM; Oxidative stress; Streptozotocin