PMID- 20053369 OWN - NLM STAT- MEDLINE DCOM- 20100413 LR - 20131121 IS - 1096-0333 (Electronic) IS - 0041-008X (Linking) VI - 244 IP - 2 DP - 2010 Apr 15 TI - Streptozotocin induced activation of oxidative stress responsive splenic cell signaling pathways: protective role of arjunolic acid. PG - 114-29 LID - 10.1016/j.taap.2009.12.024 [doi] AB - 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. CI - Copyright 2009 Elsevier Inc. All rights reserved. FAU - Manna, Prasenjit AU - Manna P AD - Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VIIM, Calcutta-700054, West Bengal, India. FAU - Ghosh, Jyotirmoy AU - Ghosh J FAU - Das, Joydeep AU - Das J FAU - Sil, Parames C AU - Sil PC LA - eng PT - Comparative Study PT - Journal Article DEP - 20100104 PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (Hypoglycemic Agents) RN - 0 (Plant Extracts) RN - 0 (Reactive Oxygen Species) RN - 0 (Triterpenes) RN - 465-00-9 (arjunolic acid) RN - 5W494URQ81 (Streptozocin) SB - IM MH - Animals MH - Diabetes Mellitus, Experimental/metabolism/*prevention & control MH - Hypoglycemic Agents/*pharmacology/therapeutic use MH - Male MH - Oxidative Stress/drug effects/*physiology MH - Plant Bark MH - Plant Extracts/pharmacology/therapeutic use MH - Rats MH - Reactive Oxygen Species/metabolism MH - Signal Transduction/drug effects/*physiology MH - Spleen/drug effects/*metabolism MH - Streptozocin/antagonists & inhibitors/*toxicity MH - Terminalia MH - Triterpenes/*pharmacology/therapeutic use EDAT- 2010/01/08 06:00 MHDA- 2010/04/14 06:00 CRDT- 2010/01/08 06:00 PHST- 2009/03/23 00:00 [received] PHST- 2009/12/02 00:00 [revised] PHST- 2009/12/17 00:00 [accepted] PHST- 2010/01/08 06:00 [entrez] PHST- 2010/01/08 06:00 [pubmed] PHST- 2010/04/14 06:00 [medline] AID - S0041-008X(09)00531-6 [pii] AID - 10.1016/j.taap.2009.12.024 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2010 Apr 15;244(2):114-29. doi: 10.1016/j.taap.2009.12.024. Epub 2010 Jan 4.