Cadmium and/or ethanol increase oxidative stress in liver of the exposed rats

By using animal model (Wistar rats) we tried to investigate singular effects of alcohol (A) and cadmium (Cd) and their parallel exposure on liver red-ox status. Leading by the fact that smokers are on a greater heath risk caused by Cd, derives from cigarette smoke and that alcoholics are mainly smokers, we tried to imitate such real life circumstances, we administered Cd intraperiotenally (i.p.) (from toxicokinetics point of view it is an adequate alternative route of administration) and A was given orally to rats.

Using this experimental model, we tried to get insight of outcomes of Cd and/or A use related to oxidative stress (OS), which might be happening in the liver of alcoholic smokers.

Adult male Wistar rats were randomly divided into four groups (n=6), according to the applied treatment during 21 days: control (C) group – untreated rats, A21 group - received daily 3 mL 20% ethanol/kg by gastric intubation, Cd21 group - 1 mg CdCl2/kg was administered i.p. and A21+Cd21 group – rats were exposed to both, A and Cd, in the same manner. Measured OS parameters in liver refer to: superoxide anion radical (O2?–), glutathione reduced (GSH) and oxidized (GSSG), malondialdehyde (MDA), activities of total superoxide dismutase (tSOD), catalase (CAT), glutathione-S-transferase (GST) and glutathione reductase (GR).

Individual exposures: 1) to A, increased MDA for 167%, O2?– for 107% and decreased GSSG for 19%, GSSG/GSH ratio for 18%; and activities of tSOD for 28% and CAT for 25%; and 2) to Cd, increased MDA for 111% and O2?– for 166% and decreased GSH for 44%; and activities of tSOD for 27%, CAT for 58%, GR for 24% and GST for 67%. Parallel exposure to both, Cd and A for 21 days resulted in elevation of MDA for 156%, O2?– for 201%, GSSG/GSH ratio for 19%, activities of CAT for 44% and GST for 207% and decrease of tSOD activity for 34%.

Our results demonstrated that A and Cd developed OS in liver by different metabolic pathways (Cd depletes GSH through ligand-chelating reactions and reduces activity of antioxidant enzymes by ion-exchanged reactions with active metals in relevant enzymes; and A acts at the level of redox reactions) and do not impose additive effect when applied together.

The most significant result of this study is that A and Cd applied individually significantly interfere with glutathione cycle in liver, contrary to parallel exposure.