This paper evaluated the chemoprotective effect of lipoic acid (LA) against microcystin (MC) toxicity in carp Cyprinus carpio. To determine the LA dose and the time necessary for the induction of three different classes (alpha, mu and pi) of glutathione S-transferase (GST) gene transcription, carp were i.p. injected with 40mg/kg lipoic acid solution. A group was killed 24h after the first i.p. injection (condition 1); another group received two i.p. injections with a 24h of interval between each one and was killed 48h after the first injection (condition 2) and a third group received one i.p. injection and was killed 48h latter (condition 3). Results showed that LA was effective in promoting an increase in GSTs gene transcription in liver only in the condition 2. A second experiment was done, where carp pre-treated with LA (condition 2) were gavaged twice with a 24h interval with 50μg MC/kg. Ninety-six hours after experiment beginning, carp were killed, and organs were dissected. Results of GST activity in liver and brain suggest that LA can be a useful chemoprotection agent against MC induced toxicity, stimulating detoxification through the increment of GST activity (brain) or through reversion of GST inhibition (liver).
Antioxidants like lipoic acid (LA) are known to trigger augmented antioxidant and phase II and III responses. This study aimed to evaluate the effect of LA in P-glycoprotein (Pgp) expression, glutathione-S-transferase (GST) activity, total antioxidant competence, levels of lipid peroxides (TBARS) and accumulation of the organochlorine insecticide endosulfan (Endo: α-, β-isomers and sulfate metabolite) in different organs of the fish Jenynsia multidentata. One hundred and twenty females (1.55±0.07 g) were fed during 8 days with (n=60) or without (n=60) a LA enriched ration (6000 mg/kg). Four experimental groups were defined: -LA/-Endo; +LA/-Endo; -LA/+Endo; and +LA/+Endo. Endo groups were exposed during 24 h to 1.4 μg of insecticide/L. Results showed that only LA induced a significant increment in liver Pgp expression. GST activity was augmented in liver after exposure to LA or Endo. TBARS levels were lowered in liver and gills after LA pre-treatment. Total antioxidant capacity was lowered in liver of Endo exposed fish, a result that was reversed by LA pre-treatment. It is concluded that LA induced the expected effects in terms of Pgp expression, GST activity and reduced TBARS levels although favored α-Endo accumulation in brain. However, the Endo metabolism to the more persistent endosulfan sulfate was not facilitated by LA pre-treatment.
We evaluated the effects of aqueous extracts of the cyanobacterium-producing microcystin (MC), Microcystis aeruginosa (strain RST9501), on detoxification capacity and glutathione (GSH) synthesis in liver, brain, gill, and muscle-as well as apoptotic protease (calpain) activity in liver and brain-in the common carp Cyprinus carpio (Teleostei: Cyprinidae). Experimental groups were defined as follows: (1) control (CTR); (2) carp treated with an aqueous extract from the toxic cyanobacteria M. aeruginosa in a final MC concentration of 25 μg/kg (MC 25); and (3) carp treated with an aqueous extract from the toxic cyanobacteria M. aeruginosa in a final MC concentration of 50 μg/kg (MC 50). Carp were gavaged with a cyanobacterial aqueous solution or MilliQ water (CTR group). The experiment was conducted for period of 48 h comprising two gavages with a 24-h interval between them. Some of the parameters analyzed in liver, brain, gill, and muscle included activity of the enzymes glutathione-S-transferase (GST), glutamate cysteine ligase (GCL), glutathione reductase (GR), and GSH concentration. We also evaluated GST pi concentration by Western blot as well as calpain activity in liver and brain samples. In carp liver from the MC 50 group, we observed a decrease in GST and GCL activity, which was accompanied by a decreased GSH concentration. In addition, liver calpain activity was highly induced in carp at both MC doses. Thus, MC ingestion affected the liver antioxidant status through decreasing the GSH concentration and the activity of the enzyme involved in its synthesis (GCL). It also decreased the MC detoxification capacity of the liver because total GST activity decreased, a result that cannot be ascribed to GST pi levels. Because GSH acts as an uncompetitive inhibitor of calpain, its decrease should explain the higher activity of this apoptotic enzyme. The main goal of this study was to show that a decrease in GSH concentration is related to decreased activity of GCL, the limiting enzyme involved in GSH synthesis. Because MCs are phosphatase inhibitors and GCL is allosterically inhibited by phosphorylation, the cellular hyperphosphorylation state induced by MC exposure could act as a modulator factor for antioxidant defenses.
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