The Effect of γ-Hexachlorocyclohexane (Lindane) on the Activities of Liver Lipogenic Enzymes and on Serum Lipids in Rats

Abstract

Abstract The effect of dietary γ-hexachlorocyclohexane (lindane) (50 -350 ppm, 0.17-1.19 μmol/kg chow) on the activity of enzymes of lipogenesis, viz., fatty acid synthase (FAS; EC 2.3.1.85), citrate cleavage enzyme (CCE; EC 4.1.3.8), malic enzyme (ME; EC 1.1.1.40), glucose-6-phosphate dehydrogenase (G 6 PDH; EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (PGDH; EC 1.1.1.44), and on serum lipid levels, was investigated in livers of 35-day-old male Wistar rats. Lindane (150 ppm) caused a substantial decline of enzyme activities within the first 24 h of treatment. The decrease was transient, however, and enzyme activities subsequently recov­ered despite continuation of lindane feeding. The recovery of enzyme activities was compara­ tively fast in the case of ME, G 6 PDH and PGDH, but very slow with FAS and CCE. Activities of lipogenic enzymes decrease when animals are starved, and increase much beyond prestarvation levels upon subsequent refeeding. Lindane in the refeeding diet blunted this overshoot of FAS and CCE activities in a dose-dependent manner. In contrast, activities of ME, G 6 PD H and PGDH responded to low dietary lindane concentrations with a substantial stimulation of the increase of activity, whereas at high lindane concentrations the overshoot was inhibited. According to their responses to lindane exposure, liver lipogenic enzymes could be grouped into 2 categories with FAS and CCE representing one and ME, G 6 PDH and PGDH representing the other group. Polychlorinated biphenyls (PCBs) in the diet caused basically opposite changes of the activities of the lipogenic enzymes. Co-administration of lindane and PCBs resulted in an apparent cancellation of effects, suggesting that lindane and PCBs affect fatty acid synthesis at opposite points. Levels of the serum triglycerides were increased significantly as a result of lindane feeding, while serum cholesterol and phospholipid levels were only slightly elevated. The increase of serum triglyceride levels that is routinely observed after refeeding of starved animals was stimulated even more by low concentrations of lindane in the refeeding diet, but inhibited by high concentrations.