Protective role of metallothionein (I/II) against pathological damage and apoptosis induced by dimethylarsinic acid

Abstract

AIM:To better clarify the main target organs of dimethylarsinic acid toxicity and the role of metallothionein (MTs) in modifying dimethylarsinic acid (DMAA) toxicity. METHODS:MT-I/II null (MT -/-) mice and the corresponding wild-type mice (MT +/+ ), six in each group, were exposed to DMAA (0-750 mg/kg body weight) by a single oral injection. Twenty four hours later, the lungs, livers and kidneys were collected and undergone pathological analysis, induction of apoptotic cells as determined by TUNEL and MT concentration was detected by radio-immunoassay. RESULTS:Remarkable pathological lesions were observed at the doses ranging from 350 to 750 mg/kg body weight in the lungs, livers and kidneys and MT +/+ mice exhibited a relatively slight destruction when compared with that in dose matched MT -/-mice. The number of apoptotic cells was increased in a dose dependent manner in the lungs and livers in both types of mice. DMAA produced more necrotic cells rather than apoptotic cells at the highest dose of 750 mg/kg, however, no significant increase was observed in the kidney. Hepatic MT level in MT +/+ mice was significantly increased by DMAA in a dose-dependent manner and there was no detectable amount of hepatic MT in untreated MT -/-mice. CONCLUSION:DMAA treatment can lead to the induction of apoptosis and pathological damage in both types of mice. MT exhibits a protective effect against DMAA toxicity.

Peculiarities of the Molecular Structure and Functions of Metallothioneins in the Central Nervous System

“…Injection of Zn-MT-II decreases the levels of interleukin-6 and tumor necrosis factor (TNF), and also decreases the intensity of apoptosis of neurons and oligodendrocytes. The level of zinc per se can also play an important role in the control of apoptosis; a decrease of this index leads to suppression of the activity of calcium-activating endonuclease and apoptotic protease [58]. Consequences of injections of MTs (similar to those mentioned above) were observed in rats after administration of 6-aminonicotinamide [59,60].…”

“…Under such conditions, the synthesis of anti-inflammatory cytokines increases [49,50], angiogenesis is intensified, [58], the survival of neurons also increases, and the processes of recovery of tissues are improved [36][37][38][59][60][61][62][63][64].…”

Apoptosis, metallothionein, and bioavailable metals in domestic mice (Mus musculus L.) from a human-inhabited volcanic area

“…The synthesis of MT is efficiently induced in several organs to cope with the excessive exposure to metals, acting as a way of neutralizing and eliminating those elements (Kägi and Kojima 1987;Mullins and Fuentealba 1998;Amaral et al 2002;Bobillier-Chaumont et al 2006). Without MT synthesis, damages in the affected organ produced by the excess of metals could be larger than those occurring in the presence of MT, since detoxification would be delayed (Jia et al 2004).…”

Coordination of intrinsic, extrinsic, and endoplasmic reticulum-mediated apoptosis by imatinib mesylate combined with arsenic trioxide in chronic myeloid leukemia

“…Metallothioneins are metal-binding proteins that maintain metal ion homoeostasis and redox balance, and may help to scavenge superoxide and hydroxyl radicals. 33 Similarly, disulfide isomerase-like proteins, located in the ER, may also be able to maintain the redox balance by catalyzing thiol-disulfide exchange reactions. Moreover, these proteins are probably involved in the oxidative folding of newly synthesized proteins.…”