Mechanisms of cadmium-induced chronotoxicity in mice

Abstract

-Biological defense factors show diurnal variations in their expression levels or activities. These variations can induce the different sensitivity to external toxicants of a day. We reported earlier that mice showed clear diurnal variation of cadmium (Cd)-induced toxicity, i.e., chronotoxicity. In this report, we investigated additional new evidences for the cadmium (Cd)-induced chronotoxicity, and considered the mechanisms contributed to this chronotoxicity. Male C57BL/6J mice were injected with CdCl 2 (6.4 mg/kg, one shot) intraperitoneally at 6 different time points of a day (zeitgeber time (ZT); ZT2, ZT6, ZT10, ZT14, ZT18 or ZT22) followed by monitoring the mortality until 14 days after the injection. We observed extreme difference in survival numbers: surprisingly, all mice died at ZT2 injection while all mice survived at ZT18 injection. Moreover, in non-lethal dose of Cd (4.5 mg/kg), the values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) used as indexes of hepatotoxicity markedly increased at ZT6 injection while mostly unchanged at ZT18 injection. To consider the mechanisms of this extreme diurnal variation, we examined biochemical studies and concluded that the diurnal variation was not caused by the differences in hepatic Cd level, basal hepatic metallothionein (MT) level, and induction level or induction speed of hepatic MT. We suggested that one of the candidate determination factors was glutathione. We believe that the "chronotoxicology" for metal toxicity may be classic, yet new viewpoint

Suppressive Effect of Kampo Formula “Juzen-taiho-to” on Carbon Tetrachloride-Induced Hepatotoxicity in Mice

“…14,15) Measurement of Hepatic Ca (Ca 2+ ) Concentration Liver specimens (0.2-0.3 g each) were digested in 0.5 mL of concentrated nitric acid (60%: Kanto Chemical, Tokyo, Japan) in glass test tubes. The digested samples were held at 80°C for 1 h, with a subsequent gradual increase in temperature (10°C/h) until the sample temperature reached 130°C.…”

FBXO6 attenuates cadmium toxicity in HEK293 cells by inhibiting ER stress and JNK activation

“…Cadmium persists in the human body because it cannot be easily excreted and its concentration increases with age (Ikeda et al, 2004). An epidemiological survey reported that higher intake of cadmium is associated with a higher incidence of renal impairment (Heilmaier et al, 1987;Lee et al, 2013;Miura et al, 2013;Summer et al, 1986;Tokumoto et al, 2014); thus, the health problems caused by cadmium are a global concern.…”

Effect of Cadmium on DNA Changes in Ipomoea aquatica Forssk.

“…Y R = 101.64X + 306.31 (R² = 0.99) (1) Y S = 38.539X + 946.76 (R² = 0.87) (2) Y L = 10.183X + 505.63 (R² = 0.91) (3) …where Y R , Y S , and Y L are the Cd concentrations in the roots, stems, and leaves, respectively, and X is the concentration of Cd in the soil.…”

“…Based on the high level of Cd accumulation in I. aquatica, plants that grow in contaminated soils are not recommended for human consumption. Cd toxicity can pose direct threats to human health via the food chain, and it can cause disease (e.g., itai-itai disease, cancer), damage to the skeletal system, adverse cardiovascular events, enzyme inhibition, DNA damage in humans [1], and chronic toxicity in animals [2]. An example of the RAPD banding patterns observed in RAPD fingerprinting experiments is shown in Fig.…”