Masataka Murakami

In vitro evaluation of cadmium-induced augmentation of the antibody response

Augmentation of in vitro primary plaque-forming cell (PFC) response by cadmium exposure was investigated. Spleen cells from 2- to 3-months-old BALBc mice were incubated with various concentrations of cadmium chloride in the presence of sheep red blood cells (SRBC) as an antigen. PFC responses were enhanced by 4 and 8 μm cadmium, but suppression of PFC responses was observed at concentrations of 20 and 40 μm cadmium. In the reconstitution of adherent and nonadherent cells to culture dishes from spleen cells which were incubated for 24 hr with 8 μm cadmium or saline (control), it was found that nonadherent cells were significantly enhanced by cadmium. Moreover, in the reconstitution between T and B cells from control and exposed groups, B cells from exposed groups were more enhanced by cadmium than T cells. These results suggested that augmentation of primary PFC response by cadmium exposure was mainly caused by the enhancement of B cells.

Significance of increase in urinary metallothionein of rats repeatedly exposed to cadmium

Cadmium chloride was injected subcutaneously (s.c.) into female Wistar rats at a dose of 1 mg Cd/kg body weight, 5 times a week up to 10 weeks. At specified intervals, 24-h urine was collected and the excreted amounts of metallothionein (MT), cadmium, copper, zinc and several indicators of renal damage were determined. Concentrations of cadmium and MT in the livers and kidneys of rats were also determined. Both cadmium and MT in the livers and kidneys were increased upon cadmium exposure. The urinary MT excretion started to increase within a week after the start of exposure. This increased excretion preceded those of enzymes and total protein as well as histopathological abnormalities in the proximal tubular cells. After the occurrence of tubular damage that disturbs reabsorption of MT, MT in urine was drastically increased. These results indicate that urinary MT levels may be an indicator not only of cadmium exposure but also of tubular damage.

Enhanced IgE Antibody Production in Mice Injected with Fly Ash

The adjuvant effect of fly ash injected via various routes on IgE antibody production was examined in mice. Primary anti-ovalbumin (OA) IgE antibody production was induced by intratracheal and intraperitoneal injection with fly ash and OA, but not by the intragastric route. Both the intratracheal and the intraperitoneal routes showed similar efficiency in inducing IgE antibody production. High secondary anti-OA IgE antibody response by exposure to aerosolized OA was also observed in mice primed with intratracheal instillation of fly ash plus OA. The activity to induce IgE antibody production by fly ash instillation was almost the same as that by aluminum silicate, studied previously. Primary and secondary anti-OA IgG antibody production was also stimulated by intratracheal instillation of fly ash. These results suggest that fly ash has an adjuvant activity in the induction of IgE and IgG antibody production in mice.

The effect of L-cysteine on the portion-selective uptake of cadmium in the renal proximal tubule

Cadmium (Cd), co-administered with an excess of L-cysteine, accumulates rapidly in the kidneys of the rat. After subcutaneous (s. c.) injection of 3 μmol CdCl2/kg body wt the concentrations of Cd in the blood and kidneys increase with the dose of cysteine over the range 0.06–5.0 mmol/kg body wt. At cysteine doses of less than 1.5 mmol/kg body wt the ratio of the concentrations of Cd in the outer medulla and cortex of the kidney remains the same as that after the injection of Cd alone. This ratio, however, is more than doubled at dose levels of 5–10 mmol cysteine/kg body wt. Hepatic uptake of Cd is unaffected by doses of cysteine below 1.5 mmol/kg body wt but decreases markedly at higher doses. In animals that are dosed simultaneously with 5 mmol cysteine/kg body wt, renal uptake of 109Cd is known to occur in the straight segments of the proximal tubules. At a dose level of less than 1.5 mmol cysteine/kg body wt the present autoradiographical studies show that 109Cd is taken up predominantly by the proximal convoluted tubules of the kidney cortex. At the critical dose level (1.5 mmol/kg body wt), cysteine decreases the retention of Cd at the s. c. injection site, but probably has little effect on the distribution of Cd between protein and other carrier molecules in the blood. This distribution, however, is altered at higher cysteine dose levels. It is suggested that, under the latter conditions, stable Cd-cysteine complexes are formed in the blood and are filtered readily through the glomeruli. These complexes are taken up in the kidney at the sites of cysteine reabsorption which, by studies with L-[35S]-cysteine, are identified as the straight segments of the proximal tubules.

Effect of pretreatment with cadmium/cysteine or metallothionein on accumulation of cadmium challenged with either complexes

The effect of pretreatment with cadmium (Cd) complexes on the distribution and accumulation of Cd in the liver and kidneys was examined for the Cd complexes that are reabsorbed site-selectively at the renal proximal tubules of rats. Cd was administered simultaneously with excess cysteine or as metallothionein (MT) and then challenged by either complex, the former complex being reabsorbed preferentially at the S3 segment of proximal tubules of the outer stripe of the outer medullary zone, while the latter complex was reabsorbed at the S1 + S2 segments of proximal tubules. Cd in the kidneys was increased by pretreatment with either complex. On the other hand, pretreatment reduced the distribution of Cd to the liver. However, no site-selective effects were observed with either complexes. Calcium concentration, which was elevated significantly in the kidneys by a single injection of both complexes, was reduced by pretreatment.

Autoradiographical studies on the localization of metallothionein in proximal tubular cells of the rat kidney.

The renal distribution of 125I-labelled metallothionein (125I-MT), administered as a tracer dose to female Wistar rats, has been investigated by light and electron microscopical autoradiography. 125I-MT was absorbed rapidly and 80% of the administered dose was observed in the kidney within 60 min after dosing. At 30 min, a high density of silver grains due to 125I, was observed by light microscopy in the convoluted proximal tubules. Electron microscopical autoradiography showed that silver grains were located in large apical vacuoles and cytoplasmic bodies (heterolysosomes) of the endocytotic system in the apical or middle regions of the cells lining convoluted proximal tubules. The results suggest that endocytotic systems are associated with 125I-MT absorption by epithelial cells lining the renal convoluted proximal tubules. The apparent inconsistency on the distribution pattern of silver grains due to 109Cd-labelled MT and 125I-labelled MT in these is also discussed.

Enhancement of antibody response in Japanese quails by acute NO2 exposure

The effect of acute exposure to nitrogen dioxide (NO2) on anti-SRBC antibody response in two lines of Japanese quails, high and low responder, was investigated. Mean survival time of 11- to 13-week-old quails after exposure to 20 ppm NO2 was 12.0 hr. The high responder line lived longer than the low responder line. Changes of spleen weights of both lines were not observed in 10- and 20-ppm NO2 exposure for 4 hr. Anti-SRBC antibody response in high responder quail was significantly enhanced by 20-ppm NO2 exposure for 4 hr and the response in low responder quail was slightly enhanced. A similar, although somewhat less pronounced, tendency was observed also after 10-ppm NO2 exposure. These results suggest that acute NO2 exposure enhances the antibody response of Japanese quails.

Road Transport Impact On the Environmental Health

Recently, in Japan, N02 concentrations have been reported higher than the standard level (0.06 ppm) in the 30 percent of automobile exhaust monitoring stations, and noise levels have been found to exceed the standard level during day and night in more than half the monitoring stations. While a new road network has been progressing rapidly in large cities, environmental protection policies such as separation of residential areas from the main busy roads have not been progressing. If such a situation continues, increases in automobile exhaust and noise due to heavy use will eventually cause more impact on residents, particularly near the roadside. At present, it would be valuable to assess the impact of road transport on residents living along the main busy road.

Some Considerations on Critical Concentration of Cadmium for Renal Toxicity in Rats

Cadmium (Cd) is a widespread toxic environmental pollutant. Environmental and occupational exposure results in the accumulation of this metal particularly in the liver and kidney and during the life-long exposure a renal Cd concentration becomes higher than a hepatic Cd concentration, which often causes renal tubular dysfunction (Friberg et al., 1985). Thus, we need to know the critical concentration of Cd to obtain information on the safety margin of exposure to this metal and the allowable daily intake levels.