Low doses of monocrotaline in rats cause diminished bone marrow cellularity and compromised nitric oxide production by peritoneal macrophages

Figures & data

Table 1.  Total food consumption, body weight gain, lactate dehydrogenase level and average severity of histological lesions of liver and kidney sections of rats treated with monocrotaline in different experimental designs.

MCT^a Treatment Level	Toxicity (Study 1) (n = 6/group)						DTH assay (Study 2) (n = 10/group)		Macrophage activity (Study 3) (n = 10/group)
	Food consumption (g)	Body weight gain (g)	LDH Level (U.I.)	Histopathology^b			Food consumption (g)	Body weight gain (g)	Food consumption (g)	Body weight gain (g)
				Lung	Liver	Kidney
0/Control	279.8 ± 10.3	62.2 ± 3.4	75 ± 27	-	-	-	330.6 ± 8.9	66.5 ± 2.3	354.3 ± 6.9	45.8 ± 2.4
1.0 mg/kg	290.5 ± 6.1	64.0 ± 2.0	94 ± 33	-	-	-	327.3 ± 8.3	62.2 ± 4.2	342.0 ± 11.5	38.0 ± 3.9
3.0 mg/kg	260.0 ± 8.3	42.3 ± 4.1**	126 ± 33	-	-	-	308.9 ± 7.5	46.9 ± 2.3**	324.0 ± 7.6*	25.6 ± 3.2*
5.0 mg/kg	Not tested	Not tested	Not tested	-	-	-	294.7 ± 6.3*	38.0 ± 2.6**	312.3 ± 7.9**	21.9 ± 4.4**
7.0 mg/kg	249.2 ± 10.4	34.3 ± 2.8**	425 ± 56**	++	+	+	Not tested	Not tested	Not tested	Not tested

^bDegree of lesions observed in 7.0 mg/kg Group: - no lesions, + mild, ++ moderate.

*p < 0.05; **p < 0.01 versus control group.

Data are expressed as mean ± SEM (n = 6–10/group).

Figure 1.  Tissue samples from rats treated with 7.0 mg MCT/kg by gavage daily for 14 days. (A) The pulmonary alveolar lumen reveals enhanced quantities of macrophages (arrows). (B) In the liver, an increased presence of megalocytosis within hepatocytes (arrows) was observed. Finally, in the renal samples (C), only a mild presence of diffused congestion is visible. Bar = 35 μm.

Table 2.  Thymic and splenic indices, thymus cortex/medulla ratio, spleen and bone marrow cellularity.

MCT treatment (n = 10/group)^a	Thymic Index^b	Splenic Index^b	Thymus C/M ratio	Spleen cellularity^c	Bone marrow cellularity^d
0.0/Control	0.16 ± 0.01	0.21 ± 0.01	3.65 ± 0.27	4.50 ± 0.4	13.90 ± 1.0
0.3 mg/kg	0.16 ± 0.01	0.21 ± 0.01	3.72 ± 0.26	4.30 ± 0.4	11.60 ± 1.4
1.0 mg/kg	0.16 ± 0.01	0.22 ± 0.00	4.33 ± 0.42	4.30 ± 0.2	12.70 ± 0.8
3.0 mg/kg	0.15 ± 0.01	0.23 ± 0.01	3.77 ± 0.34	4.60 ± 0.3	9.30 ± 1.4*

^aRats were treated with indicated doses of monocrotaline, by gavage, for 14 days.

^bg/100 g of body weight.

^cNumber of splenocytes (× 10⁸/g of spleen).

^dNumber of nucleated cells (× 10⁶).

*p < 0.05 versus control group.

Data are expressed as mean ± SEM (n = 10/group).

Table 3.  Anti-SRBC titers, plaque-forming cell (PFC) levels, and delayed type hypersensitivity (DTH) responses.

MCT treatment (n = 10/group)^a	Anti-SRBC titer^b	Plaque-forming cells^c (PFC/10^5 splenocytes)	DTH^d (%)
0.0/Control	8.25 ± 0.37	18.8 ± 2.4	17.4 ± 0.9
0.3 mg/kg	8.78 ± 0.22	17.9 ± 2.9	—
1.0 mg/kg	8.90 ± 0.35	24.5 ± 4.5	20.4 ± 1.0
3.0 mg/kg	8.80 ± 0.44	23.4 ± 3.6	20.3 ± 0.6
5.0 mg/kg	—	—	20.5 ± 1.2

^aRats were treated with indicated doses of monocrotaline, by gavage, for 14 days.

^bReported as log₂ of the reciprocal of the last dilution in which agglutination was observed.

^cMean PFC/10⁵ splenocytes obtained from two slides containing samples from each rat.

^dCalculated by subtracting the saline-injected left footpad thickness from the KLH-injected right footpad thickness; expressed as a percentage of left footpad thickness.

Data are expressed as mean ± SEM (n = 10/group).

Figure 2.  Effects on (A) phagocytosis, (B) spontaneous and phorbol myristate-acetate-induced H₂O₂ release, and (C) spontaneous or lipopolysaccharide-induced nitric oxide production by resident peritoneal macrophages of rats treated with vehicle (control), 1.0; 3.0 or 5.0 mg/kg of MCT for 14 days (n = 10/group). Results represent means ± SEM. *p < 0.05; **p < 0.01 versus control group.