Therapeutic Effect of Artemether in an Experimental Model of Nephrosis

Figures & data

Figure 1  Time course of the mean values of proteinuria in different groups of N, P, At in experimental nephrosis. N, normal rats (n = 8); P, patient (nontreated) rats that show increase of proteinuria levels after day 6 (n = 11); At, treated group by intramuscular (i.m.) injection of artemether, 5 mg/kg (n = 11). Note: A single intravascular injection of adriamycin (7.5 mg/kg body weight) induced a severe nephrotic syndrome. Onset of i.m. administration of artemether was day 6 (after development of disease). There were significant differences between nontreated (P) and artemether-treated rats (At). p < .05 was considered to be significant.

Figure 2  Effect of artemether on urine parameters in groups: N, normal (8); P, patient (11); At, treated rats with artemether (11); and E, experimental healthy control receiving artemether. Each bar represents mean ± SD. p < .05 vs. nontreated. (A) Comparison of antiproteinuric effect of artemether between groups N, P, At, and E at the end of experiment (day 49); At vs. P was significant. (B) Concentration of urine sodium in groups N, P, At, and E; At vs. P was significant. (C) Amounts of urine urea nitrogen in groups N, P, At, and E; At vs. P was significant.

Figure 3  Effect of artemether on serum creatinine in different groups: N, normal (8); P, patient (11); At, treated with artemther (11); E, experimental healthy control receiving artemther (8). Each bar represents the mean ± SD. Treatment with artemether showed a significant reduction in creatinine level compared with the patient group (p < .05).

Figure 4  Effect of artemether on serum cholesterol level in groups: N, normal (8); P, patient (11); At, Treated with artemther (11); E, experimental healthy control receiving artemther (8). Each bar represents the mean ± SD. Decrease in cholesterol concentration in group At vs. P was significant (p < .05).

Figure 5  Representative histopathologic slides of kidney specimens of a healthy rat (N), a control rat with adriamycin-induced nephropathy (P), a nephrotic animal treated with artemether (At), and healthy controls receiving ART (E). The rats that had been treated with artemether show significantly fewer signs of glomerular destruction (hematoxyline-eosin; original magnification × 40).

Table 1  Light microscopic findings of kidney histologic lesions in various groups.

Groups	No. of rats	Hypercellularity	PMN infiltration	Karyorrhexis	Wire loops	Hydropic change	Hyalin cast	Mononuclear cell infiltration
N	8	0.3 ± 0.3	0	0.2 ± 0.2	0.3 ± 0.2	0.3 ± 0.2	0	0
P	11	2.6 ± 0.3	1.3 ± 0.2	1.3 ± 0.3	2.0 ± 0.2	1.1 ± 0.1	2.6 ± 0.2	1.8 ± 0.3
At	11	0.5 ± 0.2	0.2 ± 0.1	0.5 ± 0.1	0.8 ± 0.1	0.3 ± 0.1	1.0 ± 0.1	1.0 ± 0.1
E	8	0.3 ± 0.2	0	0.1 ± 0.1	0.3 ± 0.1	0.1 ± 0.3	0	0

Values are expressed as mean ± SEM.Semiquantitative scoring of histologic lesions shows, a significant difference between group P vs. N and also P vs. At in hypercellularity, PMN infiltration, karyorrhexis, wire loops, hydropic change, hyalin cast, and mononuclear cell infiltration, whereas there was no significant difference between N vs. E. Treatment with artemether could significantly reduce histologic lesions in kidney.

Table 2  Effect of artemether on serum determinants.

Groups	No. of	BUN rats(mg/dL)	Cholesterol (mg/dL)	Triglyceride (mg/dL)	Creatinine (mg/dL)	Potassium (mEq/L)	Sodium (mEq/L)	Albumin (g/dL)
N	8	26 ± 4	60 ± 8	174 ± 55	0.7 ± 0.2	4.7 ± 0.3	137 ± 6	6.5 ± 0.7
P	11	29 ± 3	250 ± 58	427 ± 62	1.4 ± 0.2	6.0 ± 0.7	159 ± 17	3.3 ± 0.5
At	11	25 ± 7	163 ± 58	360 ± 149	0.9 ± 0.2	5.1 ± 1.0	162 ± 5	5.6 ± 0.5
E	8	21 ± 5	75 ± 12	88 ± 27	0.7 ± 0.1	4.7 ± 1.2	143 ± 9	5.8 ± 0.3

Values are expressed as mean ± SD. N, normal; P, patient; At, artemether-treated rat; E, experimental healthy group under challenge with 12 intramuscular injections of 5 mg/kg/48 h artemether. Decrease in cholesterol and creatinine and increase in level of albumin in treated group with artemether compared with patient group was significant In addition, reduction of triglyceride in E compared with N group was significant (p < .05).

Table 3  Effect of artemether on urine determinants.

Groups	No. of rats	Protein (mg/24h)	Urea (mg/dL)	Creatinine (mg/dL)	Potassium (mEq/L)	Sodium (mEq/L)
N	8	6.0 ± 0.4	720 ± 113	151 ± 16	71 ± 14	45 ± 5
P	11	118 ± 15	723 ± 226	185 ± 45	64 ± 9	38 ± 8
At	11	48 ± 21	414 ± 185	150 ± 18	74 ± 10	28 ± 6
E	8	3.4 ± 0.5	511 ± 211	200 ± 10	53 ± 6	26 ± 6

Data represent mean ± SD. N, normal; P, patient; At, artemether-treated rat; E, experimental healthy group under challenge with 12 intramuscular injections of 5 mg/kg/48 h artemether. Treatment with artemether caused a significant reduction in level of urine protein, urea, and sodium compared with group P. Moreover, difference between N and E groups in amounts of urine sodium, potassium, and urea were significant. p < .05 was considered to be significant.