ABSTRACT
Since a number of food and food products contain 2,4-hexadienal (HX), an unsaturated aldehyde, human exposure to HX is likely. Long term HX feeding to rodents induces forestomach cancers. Aldehyde dehydrogenases (ALDH) are key enzymes in the stomach for the metabolism of aldehydes. We examined the effect of short term feeding of HX on ALDH activity using HX as the substrate (HXDH) in different tissues of the GI tract. Feeding HX at a dose of 200 mg/kg body weight/day to post-suckling rats for 5 days elevated HXDH activity in the forestomach and esophagus but not in the glandular stomach, liver, small intestine or kidney. The induction of HXDH by HX was evident at 12.5 mg/kg dose and showed a dose-dependence up to 200 mg/kg. Increase in HXDH was time dependent but detectable after the first feeding (1 day). A similar dose (200 mg/kg) of acetylaldehyde or ethanol had no effect on HXDH activity. The increase in HXDH level in the forestomach and esophagus was transient. HXDH activity returned to normal 4 days after withdrawal of HX. Zymograms of gastric HXDH isozyme patterns in control and HX-fed counterparts were similar but showed selective increase in two particular forms in the forestomach. It is possible that these isoforms metabolize HX differently resulting in an accumulation of potential carcinogenic metabolites within the forestomach.
Subject(s)
Aldehyde Dehydrogenase/metabolism , Aldehydes/toxicity , Alkadienes/toxicity , Animals, Newborn/physiology , Stomach/enzymology , Aldehydes/metabolism , Alkadienes/metabolism , Animals , Body Weight/drug effects , Dose-Response Relationship, Drug , Esophagus/metabolism , Kinetics , L-Lactate Dehydrogenase/metabolism , Lipid Peroxidation , Organ Size/drug effects , Rats , Rats, Sprague-Dawley , Stomach/drug effectsABSTRACT
Many foods contain the unsaturated aldehyde, hexadienal (HX). Human exposure is thus unavoidable. HX feeding to rodents caused cancers only in the forestomach. Aldehyde dehydrogenases (ALDH) are key enzymes in the metabolism of aldehydes. We examined the distribution of ALDH using HX as the substrate (HXDH) along the GI tract of adolescent rats and found that their stomachs have high levels of HXDH activity and the enzyme preferred HX > 9-cis-retinal > acetyl aldehyde > formyl aldehyde. We also followed the postnatal development of the stomach. At birth, the forestomach represented 40-50% of the total stomach weight. Both fore- and glandular stomach gained weight, with the glandular portion gaining at a faster rate. By 21 days, the forestomach was 24-28% of the total weight and decreased slightly to an adult level of 22-24%. Gastric HXDH is low from birth to 14 days of age. HXDH activity increased thereafter, reaching higher levels at 21 days and peaking around 30-36 days of age. The activity then decreased to the adult level. The fore- and glandular stomach had the same level of HXDH activity in the newborn and at 7 and 14 days of age. At weaning, HXDH activity was higher (3x) in the forestomach than in the glandular stomach. In adults, the forestomach still had 2x the HXDH activity compared to the glandular stomach. Zymograms showed similar isozyme patterns of HXDH but with different ratios of the three major forms between the forestomach and the glandular stomach. Results indicate a differential development of HXDH between the fore- and glandular stomach that might be related to the higher sensitivity of the forestomach to HX feeding.
