title: Streptozotocin induced activation of oxidative stress responsive splenic cell signaling pathways: protective role of arjunolic acid.
abstract: Present study investigates the beneficial role of arjunolic acid (AA) against the alteration in the cytokine levels and simultaneous activation of oxidative stress responsive signaling pathways in spleen under hyperglycemic condition. Diabetes was induced by injection of streptozotocin (STZ) (at a dose of 70 mg/kg body weight, injected in the tail vain). STZ administration elevated the levels of IL-2 as well as IFN-gamma and attenuated the level of TNF-alpha in the sera of diabetic animals. In addition, hyperglycemia is also associated with the increased production of intracellular reactive intermediates resulting with the elevation in lipid peroxidation, protein carbonylation and reduction in intracellular antioxidant defense. Investigating the oxidative stress responsive cell signaling pathways, increased expressions (immunoreactive concentrations) of phosphorylated p65 as well as its inhibitor protein phospho IkappaBalpha and phosphorylated mitogen activated protein kinases (MAPKs) have been observed in diabetic spleen tissue. Studies on isolated splenocytes revealed that hyperglycemia caused disruption of mitochondrial membrane potential, elevation in the concentration of cytosolic cytochrome c as well as activation of caspase 3 leading to apoptotic cell death. Histological examination revealed that diabetic induction depleted the white pulp scoring which is in agreement with the reduced immunological response. Treatment with AA prevented the hyperglycemia and its associated pathogenesis in spleen tissue. Results suggest that AA might act as an anti-diabetic and immunomodulatory agent against hyperglycemia.
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VIIM, Calcutta-700054, West Bengal, India.
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Manna
authors.forename: Jyotirmoy
authors.initials: J
authors.lastname: Ghosh
authors.forename: Joydeep
authors.initials: J
authors.lastname: Das
authors.forename: Parames C
authors.initials: PC
authors.lastname: Sil
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*; D013311:Streptozocin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D029766:Terminalia; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D014315:Triterpenes; C061640:arjunolic acid; D013311:Streptozocin