ABSTRACT
Cyclophosphamide (CPX) is an anticancer drug with immunosuppressive properties. Its adverse effects are partly connected to the induction of oxidative stress. Some studies indicate that water-soluble derivative of morin-morin-5'-sulfonic acid sodium salt (NaMSA) exhibits strong antioxidant activity. The aim of present study was to evaluate the effect of NaMSA on CPX-induced changes in oxido-redox state in rat. Experiment was carried out on Wistar rats divided in three experimental groups (N = 12) receiving: 0.9% saline, CPX (15 mg/kg) or CPX (15 mg/kg) + NaMSA (100 mg/kg), respectively, and were given intragastrically for 10 days. Malondialdehyde (MDA) and glutathione (GSH) concentrations and superoxide dismutase (SOD) activity were determined in liver and kidneys. Catalase (CAT) activity was assessed only in liver. Treatment with CPX resulted in significant decrease in MDA level in both tissues, which was completely reversed by NaMSA treatment only in liver. In comparison to the control group significant decrease in SOD activity were observed in both tissues of CPX receiving group. In kidneys this parameter was fully restored by NaMSA administration. CPX evoked significant decrease in GSH concentration in kidneys, which was completely reversed by NaMSA treatment. No significant changes were seen in GSH levels and CAT activity between all groups in liver. Results of our study suggest that CPX may exert significant impact on oxido-redox state in both organs. NaMSA fully reversed the CPX-induced changes, especially MDA level in liver, SOD activity and GSH concentration in kidneys and it may be done by enhancement of activity/concentration of endogenous antioxidants.
Subject(s)
Antioxidants/pharmacology , Flavonoids/pharmacology , Kidney/drug effects , Liver/drug effects , Oxidative Stress/drug effects , Sulfonic Acids/pharmacology , Animals , Antineoplastic Agents , Catalase/metabolism , Cyclophosphamide , Female , Glutathione/metabolism , Immunosuppressive Agents , Kidney/metabolism , Liver/metabolism , Male , Malondialdehyde/metabolism , Oxidation-Reduction , Rats , Rats, Wistar , Superoxide Dismutase/metabolismABSTRACT
The involvement of nitric oxide in the gastroprotective effect of ACEA (arachidonyl-2-chloroethylamide), a selective cannabinoid CB1 receptor agonist, on aspirin-induced gastric ulceration was studied in rats. ACEA (3 mg/kg i.p.) significantly reduced gastric ulcer formation. The gastroprotection of ACEA was attenuated by pretreatment with L-NAME (25 and 50 mg/kg i.p.), a nitric oxide synthase inhibitor. The combination of L-arginine (300 mg/kg i.v.), a precursor of nitric oxide with L-NAME (50 mg/kg i.p.) reversed the protective activity of ACEA (3 mg/kg i.p.). These results suggest that endogenous nitric oxide may be involved in the protective effect of ACEA.
