Search

Arsenicosis, due to contaminated drinking water, is a serious health hazard in terms of morbidity and mortality. Arsenic induced free radicals generated are known to cause cellular apoptosis through mitochondrial driven pathway. In the present study, we investigated the effect of arsenic interactions with various complexes of the electron transport chain and attempted to evaluate if there was any complex preference of arsenic that could trigger apoptosis. We also evaluated if chelation with monoisoamyl dimercaptosuccinic acid (MiADMSA) could reverse these detrimental effects. Our results indicate that arsenic exposure induced free radical generation in rat neuronal cells, which diminished mitochondrial potential and enzyme activities of all the complexes of the electron transport chain. Moreover, these complexes showed differential responses towards arsenic. These early events along with diminished ATP levels could be co-related with the later events of cytosolic migration of cytochrome c, altered bax/bcl(2) ratio, and increased caspase 3 activity. Although MiADMSA could reverse most of these arsenic-induced altered variables to various extents, DNA damage remained unaffected. Our study for the first time demonstrates the differential effect of arsenic on the complexes leading to deficits in bioenergetics leading to apoptosis in rat brain. However, more in depth studies are warranted for better understanding of arsenic interactions with the mitochondria., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Exposure of a freshwater fish Cyprinus carpio to the sublethal concentration of mercury (0.1 mg L-1) and zinc (6.0 mg L-1) resulted in distinct changes in the energy metabolism of gill, liver and muscle at 1, 15 and 30 days. The changes were: (a) The rate of oxygen consumption and SDH activity decreased in the organs of mercury-exposed fish at all the three exposure periods in the order 1 > 15 < 30 days. Whereas, an increase was observed in these parameters in the organs of zinc-exposed fish in the order 1 > 15 > 30 days. (b) The activity of LDH and the levels of pyruvate and lactate increased in all the three organs of the fish at the three exposure periods studied in both the metal media. But, this increase was also in the order 1 > 15 < 30 days and 1 > 15 > 30 days in the organs of the fish exposed to mercury and zinc, respectively. (c) The results indicated greater reliance of mercury exposed fish on the energetically less efficient anaerobic glycolysis as the oxidative metabolism suppressed, and the dependency of zinc-exposed fish on both the oxidative and anaerobic glycolytic pathways in order to meet the energy requirements. On prolonged exposure zinc-exposed fish could adapt to sublethal toxic stress, such type of adaptive-response was not observed in mercury-exposed fish.

It was shown that the vagotomy leads to the elevation of the activity of alkaline phosphatase (AP) 7 days after the operation and to the decrease of its activity 30 days after the operation, and to the decrease of the activity of succinic dehydrogenase (SDG) 7 and 30 days after the operation. Introduction of dibunol leads to normalization of these disturbances of the activity of AP and SDG induced by vagotomy.

The effects of cadmium on the energy metabolism of mitochondria were studied with isolated hepatocytes and rat liver mitochondria. It was found that cadmium inhibited the respiration of both isolated hepatocytes and mitochondria and decreased the ATP content of isolated hepatocytes. This inhibition of energy metabolism of mitochondria was highly related to the nonviability of isolated hepatocytes caused by cadmium. The site of electron transport of the mitochondrial respiratory chain blocked by cadmium was located between cytochrome b and flavo-proteins. The uncoupling effects of mitochondrial oxidative phosphorylation caused by cadmium may have resulted from changes in the fluidity and permeability of the mitochondrial membrane.