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Verapamil protection against mercuric chloride-induced renal glomerular injury in rats
1Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
Abstract:
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.
Insights
Verapamil, a calcium channel blocker, protects rat kidneys from mercury-induced damage. It prevents structural changes, protein loss, and cellular infiltration in glomeruli, indicating a direct protective effect on kidney cells.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Mercuric chloride (HgCl2) induces significant renal glomerular structural damage.
- Calcium influx into glomerular cells is implicated in HgCl2 nephrotoxicity.
Purpose of the Study:
- To investigate the protective effects of verapamil, a calcium channel blocker, against HgCl2-induced nephrotoxicity in rats.
- To elucidate the role of calcium in HgCl2-induced glomerular damage.
Main Methods:
- Rats were pretreated with verapamil before HgCl2 administration.
- Glomerular cross-sectional area (GCSA), calcium content, fibronectin and lipid deposition, and leukocyte infiltration were assessed.
- In vitro studies evaluated HgCl2's effect on GCSA.
Main Results:
- Verapamil pretreatment prevented HgCl2-induced glomerular proteinuria and GCSA reduction.
- Verapamil normalized elevated glomerular calcium content, fibronectin, lipid deposition, and leukocyte infiltration.
- HgCl2 induced GCSA contraction in vitro, which verapamil prevented.
Conclusions:
- Verapamil effectively protects against HgCl2-induced nephrotoxicity by mitigating structural damage and cellular infiltration.
- The findings suggest that HgCl2 nephrotoxicity involves direct effects on glomerular cells, potentially mediated by calcium influx.