Verapamil protection against mercuric chloride-induced renal glomerular injury in rats.
We have examined the effects of the calcium channel blocker verapamil on the renal glomerular structural damage produced by mercuric chloride in rats. Verapamil (75 micrograms/kg body wt iv) was administered 30 min prior to mercuric chloride injection (HgCl2, 5 mg/kg body wt sc). Verapamil prevented the glomerular proteinuria observed in HgCl2-treated rats. Isolated glomeruli from mercury-treated rats 1 h after injection presented a diminished cross-sectional area as compared with control glomeruli (control [micron2], 26,310 +/- 2545; HgCl2 [micron2], 18,474 +/- 1828) and increased glomerular calcium content (control, 23 +/- 6 nmol/mg protein; HgCl2, 43 +/- 7 nmol/mg protein). Verapamil pretreatment prevented glomerular cross-sectional area (GCSA) diminution and glomerular calcium content rise (GCSA [micron2] Vp + Hg, 28,281 +/- 4654, Ca2+ [nmol/mg protein] Vp + Hg, 18 +/- 5). Renal sections prepared for immunohistochemical detection and histochemical analysis showed increased deposits of fibronectin and lipids and enhanced cellularity in glomerular structures from HgCl2-treated rats. Renal sections from animals pretreated with verapamil showed fibronectin and lipid contents not different from control sections and their histological studies did not show any changes when compared with control. Verapamil pretreatment also protected glomeruli from enhanced leukocyte content (myeloperoxidase activity/mg protein): control, 59 +/- 7; HgCl2, 134 +/- 10; Vp + Hg, 79 +/- 11). HgCl2 also contracts GCSA in vitro; Vp prevented this GCSA diminution. The results described in this study indicate that mercuric chloride nephrotoxicity may be associated not only with changes in renal glomerular haemodynamics, but also with a direct effect on glomerular cells.
Girardi
G
G
Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
Elías
M M
MM
D000818:Animals; D001806:Blood Urea Nitrogen; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D005353:Fibronectins; D020011:Protective Agents; D008627:Mercuric Chloride; D014700:Verapamil; D009195:Peroxidase; D002118:Calcium