Prevention and partial reversal of diabetes-induced changes in enteric nerves of the rat ileum by combined treatment with alpha-lipoic acid and evening primrose oil.
Treatment with alpha-lipoic acid (LA) or evening primrose oil (EPO), individually, fails to prevent diabetes-induced changes in enteric nerves. Since synergy between these treatments has been reported, the aim was to investigate the effectiveness of combined LA/EPO treatment. LA and EPO were administered in the diet (approximately 80 and 200 mg/kg/day, respectively) to control and diabetic (induced by streptozotocin, 65 mg/kg, i.p.) rats. For prevention, treatment started after 1 week and lasted 7 weeks. For reversal, treatment lasted 4 weeks and was initiated after 8 weeks. Nerves supplying the ileum containing vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and noradrenaline (NA) were examined immunohistochemically or biochemically. Diabetes caused a significant increase in VIP-containing cell bodies (p<0.001), decrease in NA content (p<0.01) and loss of CGRP-immunoreactivity. LA/EPO treatment totally prevented diabetes-induced changes in VIP (p<0.001) and CGRP and partially reversed (p<0.05) these changes once they had been allowed to develop. In contrast, treatment had no effect on diabetes-induced changes in NA-containing nerves. Therefore, LA and EPO are only effective at treating diabetes-induced changes in some enteric nerves when administered in combination. However, diabetes-induced changes in NA-containing nerves are resistant to treatment.
Shotton
Hannah R
HR
Department of Anatomy and Developmental Biology, Autonomic Neuroscience Institute, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK.
Broadbent
Steven
S
Lincoln
Jill
J
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000473:pathology; D003929:Diabetic Neuropathies / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005228:Fatty Acids, Essential / Q000008:administration & dosage*; D007082:Ileum / Q000294:innervation; D007150:Immunohistochemistry; D008041:Linoleic Acids; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009638:Norepinephrine / Q000378:metabolism; D031665:Oenothera biennis; D010938:Plant Oils; D051381:Rats; D017208:Rats, Wistar; D008063:Thioctic Acid / Q000008:administration & dosage*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism; D017965:gamma-Linolenic Acid
D005228:Fatty Acids, Essential; D008041:Linoleic Acids; D018696:Neuroprotective Agents; D010938:Plant Oils; D014660:Vasoactive Intestinal Peptide; C028498:evening primrose oil; D008063:Thioctic Acid; D017965:gamma-Linolenic Acid; D015740:Calcitonin Gene-Related Peptide; D009638:Norepinephrine