Methylmercury intoxication activates nitric oxide synthase in chick retinal cell culture

Abstract

The visual system is a potential target for methylmercury (MeHg) intoxication. Nevertheless, there are few studies about the cellular mechanisms of toxicity induced by MeHg in retinal cells. Various reports have indicated a critical role for nitric oxide synthase (NOS) activation in modulating MeHg neurotoxicity in cerebellar and cortical regions. The aim of the present study is to describe the effects of MeHg on cell viability and NOS activation in chick retinal cell cultures. For this purpose, primary cultures were prepared from 7-dayold chick embryos: retinas were aseptically dissected and dissociated and cells were grown at 37ºC for 7-8 days. Cultures were exposed to MeHg (10 µM, 100 µM, and 1 mM) for 2, 4, and 6 h. Cell viability was measured by MTT method and NOS activity by monitoring the conversion of L- [H 3 ]-arginine to L-[H 3 ]-citrulline. The incubation of cultured retina cells with 10 and 100 µM MeHg promoted an increase of NOS activity compared to control (P < 0.05). Maximum values (P < 0.05) were reached after 4 h of MeHg incubation: increases of 81.6 ± 5.3 and 91.3 ± 3.7%, respectively (data are reported as mean ± SEM for 4 replicates). MeHg also promoted a concentration-and timedependent decrease in cell viability, with the highest toxicity (a reduction of about 80% in cell viability) being observed at the concentration of 1 mM and after 4-6 h of incubation. The present study demonstrates for the first time the modulation of MeHg neurotoxicity in retinal cells by the nitrergic system.

Feeding mice with diets containing mercury-contaminated fish flesh from French Guiana: a model for the mercurial intoxication of the Wayana Amerindians

“…When addressing the question as to whether mouse is a pertinent model for the mercurial intoxication of the Wayana Amerindians, a good criterion consists in a comparison of the mercury concentrations impairing cell life, i.e. resulting in cell death or limited cell viability, among various cell lines from different origins (Table 9 ) including bacteria [ 45 ], yeast [ 46 ], clam [ 47 ], worm [ 48 ], mosquito [ 49 ], chicken [ 50 ], fish [ 51 ], rabbit [ 52 ], rat [ 31 , 53 , 54 ], mouse [ 32 , 53 , 55 , 56 ], and man [ 57 - 59 ]. Remarkably, most of these values are ranging between 1 to 10 μM methylmercury whatever the considered organism, from bacteria to man, and for different cell types.…”

Methylmercury Alters the Activities of Hsp90 Client Proteins, Prostaglandin E Synthase/p23 (PGES/23) and nNOS

“…H 2 O 2 , superoxide anion ( ˙ O 2 –) and nitric oxide (NO) levels are increased in cultured neurons, astrocytes and in rodent brains following MeHg exposure [13] , [14] . Putative mechanisms of MeHg-induced free radical generation include inhibition of mitochondrial electron transport chain complexes II and III, alterations in antioxidant enzyme function, and activation of nitric oxide synthase (NOS) [15] , [16] , [17] . Additionally, as an electrophile, MeHg reacts readily with thiol and selenol groups on proteins as well with GSH, leading to inhibition of enzymes and alteration of protein structure.…”

Cerebellotoxic Agents

“…The expression of vascular endothelial growth factor (VEGF), a powerful angiogenic growth factor, increases in the cerebellum, and to a lesser degree in the occipital lobe, following exposure (Takahashi et al 2017). Methylmercury impairs nitrergic activity, both in vitro and in vivo (Herculano et al 2006;Himi et al 1996). Animal studies suggest that NMDA receptor activation and a consecutive rise in nitric oxide levels play a primary role in neurodegeneration due to methylmercury intoxication (Yamashita et al 1997).…”