Renal protective effect of molsidomine and L-arginine in ischemia-reperfusion induced injury in rats.
BACKGROUND
Nitric oxide (NO), synthesized from L-arginine by the enzyme NO synthase (NOS) seems to play an ambiguous role during tissue ischemia-reperfusion (I/R) injury. This study was designed to investigate the effects of molsidomine, a NO donor and L-arginine in I/R induced renal failure in rats


METHODS
The protective effect of molsidomine and L-arginine against the damage inflicted by I/R was investigated in Sprague-Dawley rats. In one set of experiments animals were unilaterally nephrectomized, and subjected to 45 min of left renal pedicle occlusion and in another set both the renal pedicles were occluded for 45 min followed by 24 h of reperfusion. Molsidomine (10 mg/kg, p.o.) was administered twice, 30 min before ischemia and 12 h after the reperfusion period, while L-arginine was administered once, 30 min before ischemia. At the end of the reperfusion period, rats were sacrificed. Tissue and urine nitrite levels were measured to assess the total NO levels. Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels, catalase (CAT), and superoxide dismutase (SOD) activities were determined in renal tissue. Serum creatinine and BUN concentrations were measured for the evaluation of renal function.


RESULTS
Ischemic control animals demonstrated severe deterioration of renal function, renal morphology, reduced levels of tissue, and urine NO levels and a significant renal oxidative stress. Pretreatment of animals with molsidomine and L-arginine markedly attenuated renal dysfunction, morphological alterations, improved the tissue as well as urine NO contents, reduced elevated TBAR levels and restored the depleted renal antioxidant enzymes.


CONCLUSIONS
The findings imply that NO play a causal role in I/R induced renal injury.
Chander
Vikas
V
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India. chandervikas2004@yahoo.co.uk
Chopra
Kanwaljit
K
D000818:Animals; D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000517:prevention & control*; D008297:Male; D023421:Models, Animal; D008981:Molsidomine / Q000494:pharmacology / Q000627:therapeutic use*; D009392:Nephrectomy; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D020030:Nitric Oxide Donors; D020011:Protective Agents; D001120:Arginine; D008981:Molsidomine