Aflatoxin B1 at a final concentration of 10-5 M depressed the sytheses of DNA, RNA and protein in cultured chick embryo liver cells. The same dose produced ultrastructural changes in the nucleus, such as nucleolar compactness or segregation of fibrillar and granular components and in the cytoplasmic area, such as vesiculation, dilatation or degranulation of endoplasmic meticulum. These acute toxic effects of aflatoxin B1 were partially decreased by an addition of 4 × 10-5 M estradiol-17β. Namely estradiol-17β significantly reduced the nucleolar compactness and segregation of fibrillo-granular components but did not improve the vesiculation, dilatation and degranulation of endoplasmic reticulum. Estradiol-17β also protected the liver cells from the aflatoxin B1-induced inhibition of nucleic acid and protein synthesis. These results suggest that the protective effect of estradiol-17β against the acute hepatotoxicity of aflatoxin B1 is mainly due to an antagonistic interaction of both compounds on the synthesis of nucleic acid in nucleolus.
The administration of sublethal pesticide doses to silkworm (Bombyx mori L.) larvae resulted in marked reproductive abnormalities: a decrease in the total number of eggs laid; an increase in the number of non-fertilized eggs; the death of embryos in the early developmental stage; the inability of embryos, developed to the stage just before hatching, to hatch; and the death of newly hatched silkworms.
The relationship of the BSP retaining capacity of organic anion binding protein in the liver to the transport of BSP from plasma to bile was examined in CCl4-treated rats. These proteins were separated into Iigandin and Z protein by Sephadex G-75 gel chromatography. The BSP retaining capacity of these proteins was significantly decreased by CCl4 administration (2.5 ml/kg, p.o.). At 3 hours after CCl4, this decreased capacity was caused mainly by the decrease in their binding affinity, at 24 hours after CCl4, however, it was accompanied by decreases in both their binding affinity and protein amounts. At 3 hours, the hepatic uptake of BSP evaluated by determination of plasma BSP concentration, the initial disappearance rate (K1), and the hepatic dye content did not differ from those in the controls, and biliary excretion of BSP was unchanged. At 24 hours, hepatic uptake and biliary excretion of BSP as well as bile flow were significantly decreased. From these results, it is suggested that the alteration in the retaining capacity of ligandin and Z protein would not be a determinant factor in the transfer of BSP from plasma to bile.
Orally administered cadmium has been known to cause diarrhea and flatulence of the gastrointestinal tract. Scanning electron micro-scopic observations revealed that the absorptive cells on the tip of the intestinal villi were affected to some extent by administration of 2.5 μg CdSO4/10 g of body weight (b.w.). Administration of higher doses of CdSO4 made the microvilli of the absorptive cells sparse and caused degeneration of the cells. Strong enzymic activities of alkaline phosphatase, acid phosphatase, magnesium-dependent ATPase, and sodium-potassium-dependent ATPase were recognized at the microvilli of the absorptive cells of the villi in the control mice. The enzymic activities of magnesium-dependent ATPase and sodium-potassium -dependent ATPase became weak with increasing dosages of CdSO4. The microvilli of the absorptive cells showed a strong alkaline phosphatase activity at a dose less than 25 μg CdSO4/10 g of b. w., while some inhibitory effects could be recognized with 50 μg/10 g of b. w. After administration of 2.5 μg CdSO4/10 g of b. w., no acid phosphatase reaction products were found only at the absorptive cells located on the tip of the villi. Administration of a large quantity more than 5 μg/10 g of b. w. strongly affected the acid phosphatase activity. It may be possible that the digestive functions are impaired by low cadmium administration.
The effects of paraquat on human embryonic somatic cells were compared with those of diquat, which is a bipyridylium compound similar to paraquat. Cell lesions, mainly fatty degeneration, were observed after staining with Sudan Black B. Both herbicides caused fatty degeneration in the cells even at a concentration of 1 ppm; paraquat also caused more vacuolar degeneration at 200 to 400 ppm, than did diquat. Paraquat caused slightly higher lactate dehydrogenase activity than did diquat. The cell mortality was examined by staining with nigrosine and calculating the number of dead and damaged cells. The cell mortality for diquat was higher than that for paraquat at all concentrations but not significantly (p < 0.05).
Acute toxicity was studied on Ketoprofen, one of the non-steroidal antiinflammatory analgesics, using SPF rats. Ketoprofen was intrarectally administered in three forms such as pure powder (KP), KP suspension in CMC solution (KP-CMC) and a mixture of KP with powdered basic materials of capsule (KP-T10). The results obtained were as follows: 1. LD50 values in terms of KP were 84 mg/kg in male rats and 122 mg/kg in female rats when KP-CMC was administered intrarectally, and 117 mg/kg in male and 92 mg/kg in female when KP-T10 was administered intrarectally., while peroral administration of KP-CMC showed LD50 values of 68 mg/kg in males and 78 mg/kg in females in terms of KP. 2. Major toxic signs of KP were ulceration on small intestines and peritonitis. Degeneration of hepathocytes and decrease in thymus lymphocytes were also observed. 3. Minimum lethal dose of KP-T10 was slightly higher than that of KP-CMC.
Ketoprofen (KP) was administered intrarectally and perorally to rabbits weighing approximately 3 kg of both sexes for a period of 13 weeks, in order to study the anorectal irritaion and chronic systemic organ toxicity of KP which was capsulated with the soft T10 capsule for rectal administration and with a hard capsule for peroral administration. Doses of capsulated drugs for one animal were 9.0 mg and 4.5 mg in terms of KP. All animals treated by these dose levels survived without showing any abnormal symptoms. Intrarectal administration of KP-T10 did not produce any mucosal lesions in digestive tracts, while peroral administration of KP with hard capsule induced ulcers in cecum or anus, and congestion in small intestines in a small number of cases. No pathological change was recognized in organs except for digestive tracts in all cases by autopsy. From the above results, it can be seen that the suppository of KP capsulated by the soft T10 does not show any irritating effect on anorectal mucosa and has no toxic effect on all organs systemically. Then, a suppository of KP-T10 can be used more harmlessly than the peroral capsulated KP.