The protective effect of malotilate was studied on the liver injury induced by carbon tetrachloride (CCl4) in mice and rats. Plasma GOT and GPT activities were used as indices for the liver injury, and the liver was histopathologically examined. A remarkable suppressing effect on the liver injury was observed when malotilate was orally given 6 hr prior to oral administration of CCl4 in mice and 3, 6 or 12 hr in rats. Malotilate was also effective in preventing the liver injury caused by intraperitoneal injection of CCl4, indicating that the protective effect is not derived from the decreased CCl4 absorption. The liver injury was suppressed even when malotilate was given 12 or 24 hr prior to oral administration of CCl4 in mice and 24, 48 or 72 hr in rats. It may be the characteristic of malotilate that the protective effect lasts for a long period. It is supposed that the effect is due not only to the inhibition of the metabolic activation of CCl4 but also the other action(s) of malotilate.
This study concerns the modifying effect of carbon tetra-chloride (CCl4) on methylazoxymethanol acetate (MAM)-induced intestinal carcinogenesis in ACI rats of both sexes. Forty five animals were given CCl4 (0.5 ml/kg body weight) through a stomach tube, followed by an i. p. injection with MAM (25 mg/kg body weight) 24 hours after CCl4 treatment. The paired administrations were done once a week for 4 weeks and animals were observed until sacrifice 30 weeks later. Pretreatment with CCl4 caused not only early death from chemical toxicity of MAM but also an increase in small-bowel tumors.
Four groups of 12 Wistar SPF rats of both sexes were fed diets containing 4-bromophenyl chloromethyl sulfone (BCS) at the levels of 0, 20, 100 or 500 ppm for 13 weeks to evaluate the subacute toxicity. Males and females in the 500 ppm group showed increases in plasma protein and calcium and a decreased A/G ratio. The values of plasma total cholesterol and uric acid increased in this female group. In addition, significant increases in both absolute and relative weights were seen in the liver, thyroid and adrenal of this group of both sexes, together with the increased kidney weight in males. All males and females in the 500 ppm group had centrilobular hepatocellular swelling of the liver consisting of proliferation of the smooth endoplasmic reticulum. Males of this group also showed increased incidences of hyalin droplet degeneration of the proximal tubular epithelium and focal tubular atrophy of the kidney. The maximum no-effect level of BCS was determined to be 100 ppm (males: 6.25 mg/kg/day, females: 6.80 mg/kg/day).
Paraquat, a popular herbicide, is known to be very toxic to man and animals. Using cultured mammalian cells (human embryo lung cell, R-66), the effect of paraquat has been studied. With autoradiography, stimulation of DNA synthesis was observed when the cells were exposed to 0.08 or 0.4μM of paraquat; however, DNA synthesis was inhibited with 40 μM of paraquat. To determine cell growth rate, accumulation of mitotic cells was determined after addition of colcemid (0.2μg/ml) into the culture medium. The ratios of mitotic cells observed were proportional to the level of DNA synthesis. And the stimulation and inhibition of cell growth were observed even after washing off paraquat from media.
The tumorigenesis and cystic lesion by a single intraperitoneal administration (ip) of N-bis (2-hydroxypropyl) nitrosamine (DHPN) for 52 weeks were studied in ddY mice. The amount of DHPN was 1000 mg/kg in group I, 500 mg/kg in group II, 250 mg/kg in group III, 125 mg/kg in group IV and 0 mg/kg in group V. The tumorigenesis of DHPN was found in the lung and liver. However, cystic lesion was observed only in the liver. Lung tumors were adenoma, adenocarcinoma and squamous cell carcinoma. As liver tumors, adenoma, hepatocellular carcinoma, cholangioma and hemangioma were observed only in the mice treated with DHPN. Incidence of cystic lesion in the liver was detected in all groups treated with DHPN. Histologically, cystic lesion of the liver showed four patterns of bile duct-like, sinusoid-like, hepatocyte-like and mixed.
A study was conducted to establish whether volatile hydrocarbons, such as propane, n-butane and iso-butane, are metabolized in mice or not. In mice having inhaled these gases, isopropanol and acetone were yielded from propane, sec-butanol and methyl ethyl ketone from n-butane, and tert-butanol from iso-butane as the respective metabolites. In addition, liver microsomes were found to contain the enzymic system participating in these metabolisms. In vitro reactions with liver microsomes produced isopropanol from propane, sec-butanol from n-butane, and tert-butanol from iso-butane. It was assumed that hydrocarbons were first converted to (ω-1)-alcohols by microsomal enzyme system and then to corresponding ketones by alcohol dehydrogenase.
Acute renal failure developed in a patient accompanied by systemic manifestations such as myopathy and skin rash. The patient, a middle aged house wife, had been taking 600 mg of germanium (Ge) preparation daily for 18 months as an elixir. The main component of the preparation was GeO2 and some organic compound was also present. Histological study of the kidney post mortem showed foamy cell transformation of glomerular epithelia, degeneration of tubular epithelia with red blood cell casts and urate crystals, and a mild proliferation of mesangial matrix. Analysis of the tissue content of Ge, prompted by her history, revealed an increased accumulation of the metal. As compared to a non-user died of liver cirrhosis, the concentration of the metal was higher particularly in the spleen (183×), thyroid gland (175×), psoas muscle (93×), jejunum (76×), and renal cortex (69×). So far, neither accumulation of Ge in humal tissue nor systemic toxicity of the Ge in human has been reported. The relevance of massive accumulation of Ge to the renal failure as well as to other systemic manifestations the patient presented remains to be clarified.