title: The neuroprotective benefit from pioglitazone (PIO) addition on the alpha lipoic acid (ALA)-based treatment in experimental diabetic rats.
abstract: In this study, we investigated the combined effect of pioglitazone (PIO) with alpha lipoic acid (ALA) on the peripheral nerves of diabetic rats. Animals were divided into 8 groups (N = 6-8) and designated according to ALA (100 mg/kg/day) and PIO (10 mg/kg/day) treatment: Normal, Normal + ALA, Normal + PIO, Normal + ALA + PIO, DM, DM + ALA, DM + PIO, and DM + ALA + PIO. After 24 weeks, current perception threshold, mechanical allodynia, oxidative stresses, intraepidermal nerve fiber density (IENFD), and axonal morphology in the sciatic nerve were compared among groups. IENFD in the DM + ALA + PIO group was significantly less reduced than in other DM groups (7.61 ± 0.52 vs. 5.62 ± 0.96, 5.56 ± 0.60, and 7.10 ± 0.70 for DM, DM + ALA, and DM + PIO, respectively P < 0.05). The mean myelinated axonal area in the sciatic nerves was significantly higher in the DM + ALA + PIO group compared with non-treated DM group (70.2 ± 3.46 vs. 61.1 ± 2.91, P < 0.05) although significant differences were not present between combination therapy and monotherapy independent of ALA or PIO. Our results demonstrated that combination therapy using PIO based on ALA can give an additional benefit in peripheral nerve preservation in diabetes. Moreover, PIO can be preferentially considered when additional glucose-lowering agent is required in DPN patients treated with ALA.
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk National University Medical School, Gungiro 20 (634-18, Keum-Am Dong), Jeonju, 561-712, South Korea, mdjinhy@jbnu.ac.kr.
authors: Heung Yong
authors: HY
authors: Jin
authors: Kyung Ae
authors: KA
authors: Lee
authors: Jin Zu
authors: JZ
authors: Wu
authors: Hong Sun
authors: HS
authors: Baek
authors: Tae Sun
authors: TS
authors: Park
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004359:Drug Therapy, Combination; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D018696:Neuroprotective Agents; D045162:Thiazolidinediones; D008063:Thioctic Acid; D000077205:Pioglitazone