Differential expression of metallothionein-1 and cytochrome p450-2a5 (cyp2a5) in mice in response to lead acetate exposure and industrial effluents in Ibadan, Nigeria

Abstract

Metallothionein-1 ( MT-1), cytochrome P450-2A ( CYP2a) and other genes are involved in the detoxification of xenobiotics such as heavy metals and toxins. Changes in their expression precede overt toxic effects and can serve as a marker for exposure to pollutants. We used a mouse experimental system and quantitative reverse transcription polymerase chain reaction to determine changes in gene expression and the direction of change, in response to exposure to lead acetate (LA) and waste water (WW) from an industrial area in Ibadan. MT-1 and CYP2a5 genes were quickly and highly induced at different exposure periods and concentrations. MT-1 was mostly downregulated by the LA exposure, but upregulated by several folds on exposure to WW. CYP2a5 expression was mostly downregulated with LA exposure. The optimum expression of MT-1 and CYP2a5 genes induced by both LA and WW was at 48 h. We conclude that rapid assays to determine the direction of change in the expression of MT-1 and CYP2a5 could be a fast and reliable method in developing countries for screening humans exposed to pollutants from industrial waste.

Chronic exposure to low doses of Pb induces hepatotoxicity at the physiological, biochemical, and transcriptomic levels of mice

“…Alya et al reported that hyperlipidemia was evident for Pb‐exposed groups leading to a potential risk for cardiovascular diseases and atherosclerosis . As for cytochrome P450, which involved in the metabolism of endogenous substances and exogenous substances including drugs and environmental compounds, our transcriptome results further demonstrated that cytochrome P‐450 is indeed involved in the detoxification of xenobiotics such as heavy metals . These important metabolic pathways of liver have been changed after Pb exposure, which might be the main reason led to declines in the relative liver weights of mice and histopathological effects.…”

“…While little is known on MT involvement in Pb‐induced hepatic toxicity, a previous study observed that Pb‐MT‐like proteins accumulated in the liver 6 hours after the intraperitoneal injection of a sub‐lethal dose of lead acetate to rat . Like MT, metal transport proteins including ZnT, copper transporter (CTR), and transferrin play crucial roles in metal homeostasis, and the expression of these proteins are easily disrupted by environmental metal exposure in mice and other experimental models . Nemmicheand Guiraud reported that Cd exposure increased the expression of divalent metal‐ion transporter 1 and caused an upregulation of ZnT1 in human BJAB cells .…”

“…The results show that chronic exposure with low doses of Pb had the potential to induce hepatotoxicity accompanied by hepatic oxidative stress, suggesting that oxidative stress plays an important role in Pb‐induced hepatotoxicity. Simultaneously, the overexpression of metal transport proteins such as MT, ZT may involve detoxification during Pb‐induced hepatotoxicity . In addition, transcriptome data macroscopically shows chronic lead exposure changes the transcription genes in the liver, as well as many important metabolic pathways and important life processes.…”

“…Real‐time polymerase chain reaction (RT‐qPCR) was performed in an Eppendorf Master Cyclerep RealPlex2 (Wesseling‐Berzdorf, Germany) tube. Oligonucleotide primers used were obtained from previous studies . Samples were normalized to GAPDH levels.…”

Metallothioneins in Earthworms: The Journey So Far

“…MTs are encoded by a multigene family which vary in their responses to different inducers including heavy metals, glucocorticoids, hormones, oxidants, strenuous exercise, superoxide and hydroxyl radicals generated by gamma radiation and cold exposure [26]. The major roles of MTs include the homeostasis of trace metals (Zn, Cu, Mn, Fe etc), protection against oxidative stress and detoxifi cation of xenobiotic metals (Pd, Cd etc) [27] and [28], metal ion transport, maintaining redox pool, scavenging of radicals and regulation of expression as explained and depicted in Figure 1 [29]. They are found in a range of organisms from microbes to mammals and reports on invertebrate MTs include nematodes [30], annelids [31]; insects [32]; the oysters [33] and various species of gastropods [34,35].…”