Therapeutic Effect of Artemether in an Experimental Model of Nephrosis

Abstract

This study was carried out to elucidate the therapeutic efficacy of a new antimalarial drug, artemether, in adriamycin-induced nephropathy. To induce experimental nephrosis, adriamycin was given once by a single intravenous injection through the tail vein. Six days after adriamycin injection, therapeutic protocol was developed by intramuscular (i.m.) administration of 5 mg/kg artemether (ART). The total of i.m. injections were 14, in which five injections were made every day and nine injections were carried out at regular 48-h intervals. The therapeutic protocol was terminated on day 28, and animals were sacrificed on day 49. Our results showed that treatment with ART caused a significant reduction in the level of proteinuria (118 ± 15 vs. 48 ± 21 mg/24 h), urine urea (723 ± 226 vs. 414 ± 185 mg/dL), and urine sodium (38 ± 8 vs. 28 ± 6 mEq/L) compared with nontreated controls. In addition, a decrease in serum cholesterol (250 ± 58 vs. 163 ± 58 mg/dL) and creatinine (1.4 ± 0.2 vs. 0.9 ± 0.2 mg/dL) and an increase in the level of serum albumin (3.3 ± 0.5 vs. 5.6 ± 0.5 g/dL) were significant in the group treated with ART compared with the patient group. Moreover, treatment with ART significantly reduced glomerular PMN and mononuclear cells infiltration, hypercellularity, karyorrhexis, wire loops and hydropic change in the capillary network within the renal cortex, as well as decreased hyalin casts. On the other hand, healthy controls receiving ART showed a significant decrease in amounts of serum triglyceride (174 ± 55 vs. 88 ± 27mg/dL), urine urea (720 ± 113 vs. 511 ± 211 mg/dL), urine sodium (45 ± 5 vs. 26 ± 6 mEq/L), and potassium (71 ± 14 vs. 53 ± 6 mEq/L) compared with the normal group, where significant reduction of urinary excretion of sodium and urea must be considered as a side effect of ART therapy. These data suggest that artemether therapy can ameliorate proteinuria and suppress the progression of glomerular lesions in an experimental model of nephrosis, and that it may be recommended as a lipid-lowering drug.

Keywords:

• Antimalarial
• artemether
• nephrosis treatment
• nephrotic syndrome
• proteinuria