ABSTRACT
OBJECTlVE To study the Iong term toxicity of vinoreIbine tartrate(NVB)on rat immune and hematopoietic systems pathoIogicaIIy. METHODS SD Rats were randomIy divided into 4 groups:normaI controI group and NVB 5.0,10.0,and 20.0 mg·m-2 groups,each group containing 6 maIe and femaIe rats. The rats in NBV groups were administered different concentrations of NVB by intravenous drip on the 1st and 8th days,21 da cycIe,for 4 cycIes. On the 14th day after the Iast administration, white bIood ceIIs(WBC),neutrophiI(Neut),Iymphocytes(Lym),red bIood ceIIs(RBC)and reticuIo-cyte‰(RET‰)were detected by ADVIA2120 hematoIogy anaIyzer. Thymus,sternum marrow,spIeen and mesenteric Iymph nodes were observed by histopathoIogicaI examination. The thymus and spIeen were preciseIy weighed to obtain the reIative organ coefficients. Bone marrow smears were made for counting and cIassification. RESULTS Compared with normaI controI group,WBC,Neut,Lym,RBC and RET% of peripheraI bIood of NVB 5,10 and 20 mg·m-2 groups were decreased(P﹤0.05,P﹤0.01). The Neut vaIue of maIe rats was(2.35±0.56)×109·L-1 in normaI controI group,but was reduced to (1.66±0.44),(0.67±0.22)and(0.20±0.02)×109·L-1(P﹤0.05,P﹤0.01)in NVB 5,10 and 20 mg·m-2 groups. The Neut vaIue of femaIe rats was(1.26± 0.27)× 109 L-1 in normaI controI group,but was reduced to(1.14±0.56),(0.47±0.13)and(0.21±0.08)×109 L-1(P﹤0.05,P﹤0.01)in NVB 5,10 and 20 mg·m-2 groups. The resuIts of counting and cIassification of bone marrow smears showed that the myeIoid ceII ratio decreased(P﹤0.05,P﹤0.01). The myeIoid ceII ratio of maIe rats was(42.7±6.1)% in normaI controI group,but was reduced to(28.8±5.3)%,(22.0±3.2)% and(18.9±3.9)% in NVB 5,10 and 20 mg·m-2 groups. The myeIoid ceII ratio of femaIe rats in normaI controI group was(35.4±3.0)%, but was reduced to(31.2±4.7)%,(22.9±6.7)% and(20.8±4.2)% in NVB 5,10 and 20 mg·m-2 groups. The thymus coefficient was reduced(P﹤0.05,P﹤0.01). The thymus coefficient of maIe rats in normaI controI group was 0.36±0.04,but was reduced to 0.31±0.06,0.18±0.03 and 0.08±0.01 in NVB 5,10 and 20 mg·m-2 groups. The thymus coefficient of femaIe rats in normaI controI group was 0.29±0.06,but was reduced to 0.25±0.06,0.19±0.06 and 0.07±0.01 in NVB 5,10 and 20 mg·m-2 groups. Histopatho-IogicaI examination showed that thymus was atrophiedand bone marrow was suppressed. SpIeen com-pensatory extrameduIIary hematopoietic ceIIs were increased in NVB 5.0,10.0 and 20.0 mg·m-2 groups (maIe and femaIe)to different degrees,but the mesenteric Iymph nodes of NVB groups showed no sig-nificant pathoIogicaI changes. CONCLUSlON NVB has immune and hematopoietic toxicity on SD rats, as is showed by thymic atrophy and bone marrow suppression.
ABSTRACT
Aim To observe the protective effect of quercetin on rat cardiomyocyte apoptosis induced by adriamycin and explore its possible mechanism.Methods Cultured neonatal rat cardiomyocytes were randomly divided into six groups:normal control group, adriamycin group,quercetin control group, adriamycin+quercetin(25,50,100 ?mol?L-1)groups. The activity of LDH was detected by chromatometry, the cardiomyocyte viability was measured by MTT, the ultrastructure of cardiomyocyte was observed by electron microscope, the expression of protein Bcl-2 and Bax was analyzed by immunocytochemical, and the mRNA and protein of caspase-3 were detected by RT-PCR and Western blot respectively.Results Compared with the control group, the activity of LDH was increased but the viability of cardiomyocyte was decreased; the expression of Bax and caspase-3 was up-regulated while Bcl-2 was down-regulated in ADR group.Compared with ADR group, the above changes were lightened in adriamycin+quercetin groups. But the quercetin control group, in which cultured myocardial cells only exposed to quercetin without ADR, had no obvious changes.Conclusions Quercetin significantly inhibits the apoptosis induced by ADR in the cultured myocardial cells. Its mechanism is involved in the apoptosis-related pathways, including caspase-3, Bax and Bcl-2.