Related Experiment Videos
Morphine stimulates superoxide formation by glomerular mesangial cells
P C Singhal1, M Pamarthi, R Shah
1Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
Abstract:
Focal glomerulosclerosis is the predominant glomerular lesion in heroin addicts. We studied whether morphine, a metabolite of heroin, could directly affect the formation of superoxide by glomerular mesangial cells. Mesangial cells preincubated with morphine (10(-8) M) showed a higher (P < 0.001) production of superoxide when compared to control cells (control) 401 +/- 21 vs. morphine 610 +/- 41 nM/mg protein/h). This effect of morphine on mesangial cells was dose dependent. Naloxone, an opiate antagonist, attenuated morphine-induced formation of superoxide by mesangial cells [control, 317 +/- 4; morphine (10(-8) M), 573 +/- 9; and naloxone (10(-8) M) + morphine (10(-8) M), 333 +/- 6 nM/mg protein/h]. We conclude that morphine enhances formation of superoxide by mesangial cells and this effect of morphine seems to be mediated through opiate receptors. Since superoxide has been demonstrated to cause mesangiolysis, we propose that morphine may be playing a role in the induction of mesangial injury in patients with opiate abuse.
Insights
Morphine, a heroin metabolite, increases superoxide production in kidney mesangial cells. This suggests morphine may contribute to kidney damage in opiate abuse patients.
Area of Science:
- Nephrology
- Toxicology
- Cell Biology
Background:
- Focal glomerulosclerosis is a common kidney lesion in heroin users.
- Heroin's metabolite, morphine, is investigated for direct effects on kidney cells.
Purpose of the Study:
- To determine if morphine directly stimulates superoxide production in glomerular mesangial cells.
- To explore the role of opiate receptors in morphine-induced superoxide formation.
Main Methods:
- Cultured rat glomerular mesangial cells were treated with varying concentrations of morphine.
- Superoxide production was measured using spectrophotometric assays.
- The effect of naloxone, an opiate antagonist, was assessed.
Main Results:
- Morphine significantly increased superoxide production in mesangial cells in a dose-dependent manner (P < 0.001).
- Naloxone partially reversed the morphine-induced increase in superoxide production.
- Control cells produced 401 +/- 21 nM/mg protein/h, while morphine-treated cells produced 610 +/- 41 nM/mg protein/h.
Conclusions:
- Morphine enhances superoxide formation by glomerular mesangial cells.
- This effect appears to be mediated via opiate receptors.
- Morphine may play a role in the mesangial injury observed in opiate abuse.