Abstract:

Objective  To elucidate the effects of serum biochemistry, pathological detection and enzymatic histochemistry in LMWF regarding drug safety evaluation. Methods  16 Beagle dogs(8 males and 8 females)were randomly divided into 4 groups(Group Veh, Group 200mg/kg/d, Group 800mg/kg/d, and Group 3000mg/kg/d of LMWF, n=4 in each group)according to the body weight. They were fed with stomach lavaging once per day and 6 day per week for 13 weeks. Serum biochemical index were tested prior to the first LMWF treatment and after the last treatment. Liver was taken and frozen in liquid nitrogen, sectioned, stained, and carried on the enzyme histochemical detection. The liver was fixed by 4% neutral formaldehyde, paraffin-embedded, HE stained, and detected by the microscopy. Results  Compared with Veh group, no obvious deviation of serum biochemistry index appeared in LMWF treated groups  (P>0.05); no evident pathological changes was found in LMWF treated liver histomorphology by microscopy observation. Both adenosine triphosphatase(ATPase) and succinate dehydrogenase(SDH) activities detected by liver qualitative observation and quantitative analysis, significantly decreased, compared with the Veh group(P<0.05). Conclusion  LMWF 3000mg/kg/d dose could reduce ATPase and SDH activities, indicating that the liver mitochondrial function may be impacted, also shows that enzyme staining method is more sensitive than biochemical and pathological Methods.

Key words: Liver; Toxicity; Enzyme; Biochemistry; Pathology; Beagle dog