Fig. 2 Body weight curves rats treated orally with DL-8280 for 4 weeks

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Transcription:

Fig. 1 Chemical structure DL-8280

Fig. 2 Body weight curves rats treated orally with DL-8280 for 4 weeks

Fig. 3 Food consumption in rats treated orally with DL-8280 for 4 weeks Fig. 4 Water consumption in rats treated orally with DL-8280 for 4 weeks

Each value represents mean }S. E. from 10 rats.

Table 3 Urinalysis data in female rats treated orally with DL-8280 for 4 weeks Table 4 Fecal occult blood reaction in rats treated orally with DL-8280 for 4 weeks

Table 5 Hematology data in male rats treated orally with DL-8280 for 4 weeks Each value represents mean }S. E. from 10 rats. P<0.05 vs control N: neutrophils, L: lymphocytes, E: eosinophils, B: basophils, M: monocytes, Table 6 Hematology data in female rats treated orally with DL-8280 for 4 weeks Each value represents mean }S. E. from 10 rats. P<0.05 vs control N: neutrophils, L: lymphocytes, E: eosinophils, B: basophils, M: monocytes,

Table 7 Serum biochemistry data in male 'rats treated orally with DL-8280 for 4 weeks Each value represents mean }S. E. from 10 rats. P<0.05 vs control Table 8 Serum biochemistry data in female rats treated orally with DL-8280 for 4 weeks Each value represents mean }S. E. from 10 rats. P<0.05 vs control

Table 9 Organ weight data in male rats treated orally with DL-8280 for 4 weeks Each value represents mean }S. E. Cecum (A): with content, Cecum (B): without content P<0.05 vs control

Table 10 Organ weight data in female rats treated orally with DL-8280 for 4 weeks Each value represents mean }S. E. Cecum (A): with content, Cecum (B): without content P<0.05 vs control

Table 11 Macroscopic findings in rats treated orally with DL-8280 for 4 weeks Number rats showing the changes 2) SAVAGE, D. C. & R. DUBOS: Alterations in the mouse cecum and its flora produced by antibacterial drugs. J. Exp. Med. 128: 97-110, 1968 3) LOESCHKE, K. E.; E. UHLICHB & R. HALBACH: Ce. cal enlargement combined with sodium transport stimulation in rats fed polyethylene glycol. Proc. Soc. Exp. Biol. Med. 142: 96-102, 1973 4) GORDON, H. A. & S. NAKAMURA: Elevated levels colloid osmotic pressure in cecal contents germfree animals. Proc. Soc. Exp. Biol. Med. 149: 46

CHEMOTHERAPY VOL.32S-1 Photo. 1 Cecum from a male control rat (left) and rat treated orally with 810mg/ kg DL-8280 Enlargement Photo. in 2 a treated Cecum (H-E for 4 weeks 1103 Photo. 4 Jejunum (H-E from a male stain, ~ 100) control noticeable 5 from 810 a rat mg/kg (H-E treated orally DL-8280 for stain, ~40) change from with eks a 810mg/kg (H-E stain, ~ male rat treated DL-8280 orally for 4 we- 100) Goblet cells in number Swelling absorptive cat change Jejunum weeks Cecum control rat with 3 male rat Photo. Photo. d (right) No No noticeable from stain, ~40) epithelial cells swelled and increased 4

CHEMOTHERAPY 1104 Photo. 6Articular cartilage condyle rat from (H-E a femoral male FEB. Photo. 7 Articular control from stain. ~100) 810 cartilage a mg/kg (H-E No noticeable mucus constituents gastrointestinal conventional 6) K.; antibiotics phology on in mucins. in rats. LOESCHKE, rats. rat femoral treated condyle orally DL-8280 for with 4 weeks stain, ~100) change Local dation male 1984 the I. stools Gastroenterol. U. KAUTZ caecal U. FOUR-WEEK A NEW transport the ch 1968 Effects and 7) 58: B.; ORAL 1 :21 `26, TOXICITY ANTIBACTERIAL Klin. area Wochens 1980 D.W. BRENTNALI., Anthropathy E.A. by N-alkyl-4-pyridon-3-carboxylic ters in superficial diarrhoea. 383 `385, MCFADZEAN: mor- matrix antibiotic-associated r. INGHAM, pathogenesis SUBACUTE SYNTHETIC and 210 `217, LoHRS: to germfree 54: & electrolyte Contribution Comparison rarefaction DALE antibacterial acids. & J.A. fused Toxicol. Let- 1977 OF AGENT, DL-8280, IN RATS TAKESHI ONODERA,FUJIO INAGE, MITSUYOSHI YOSHIDA, MICHIYUKIKATO and AKIMOTO YAMADA Research Institute, Daiichi Seiyaku Co., Ltd. Subacute toxicity DL-8280, a new synthetic antibacterial agent, was investigated in rats by 4-week consecutive administration a daily dose 30, 90, 270 or 810 mg/kg. At a dose 30 or 90 mg/kg, no changes were seen in rats except for cecal enlargement which might be attributed to alteration in intestinal bacterial flora. Rats treated with 270 mg/kg showed diarrhea, staring coat, growth retardation, lower food consumption, higher water consumption, lower urinary sodium excretion and swelling jejunal goblet cells. In addition to these changer, higher serum alkaline phosphatase activity, swelling cecal absorptive epithelial cells, swelling duodenal goblet cells and rarefaction articular cartilage matrix were observed in rats given 810 mg/kg. From these results, no-effect dose DL-8280 was considered to be 90 mg/kg under the present experimental condition.

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