ABSTRACT
Aims: Oxidative stress sequel to hypertension exacerbates the clinical condition and accelerates associated organopathies, therefore prevention is important. Traditionally in Nigeria, hypertension is treated with Annona muricata L. leaves or Curcuma longa L. rhizomes, two medicinal plants with antioxidant properties. Study Design: This study assessed the effect of these plants on hypertension-induced oxidative stress in uninephrectomized Wistar rats daily loaded with 1% sodium chloride. Place and Duration of Study: Department of Veterinary Pharmacology and Toxicology Experimental Animal House, University of Ibadan, Nigeria, between August and November 2017. Methodology: Hypertensive rats were treated with methanol extracts of the plants for 42days. Two other groups of hypertensive rats were treated with lisinopril or chlorothiazide. Blood pressure was monitored by non-invasive tail plethysmography using an electro-sphygmomanometer. Oxidative stress markers were determined in blood and tissue (heart, kidney and liver); GPX, GST, GSH, SOD, MDA and NO. Results: Treatment of uninephrectomized rats with A. muricata or C. longa significantly (p<0.0001) decreased blood pressure and MDA, while elevating enzymatic and non-enzymatic antioxidant defense mechanisms of GST, GSH, GPx and SOD, comparable to normotensive rats. NO, the ubiquitous molecule required for basal vascular tone, myocardial contractility regulation and platelet adhesion prevention, was restored in the extract-treated rats. However, hypertensive untreated rats showed evidence of oxidative damages with significant increase in MDA, especially in the heart and liver, with decreases in the antioxidant defense system. Conclusion: Results of this study justified the traditional use of A. muricata or C. longa for management of hypertension in Nigeria and showed that the extracts ameliorated oxidative damage that accompanied hypertension, thus also preventing complications of hypertension.
ABSTRACT
Background: The study was aimed at investigating the effect of dosing intervals on gentamicin nephrotoxicity in puppies. Methods: Local puppies were assigned to Groups A and B (n=6) and administered gentamicin intramuscularly once (6 mg/kg) or twice (3 mg/kg) daily, respectively, for 5 consecutive days. Biochemical parameters such as urine protein, creatinine, ɤ-glutamyl transferase, as well as serum creatinine (SCR) and urea nitrogen were determined spectrophotometrically using specific kits before and after treatment. Peak and trough serum concentrations of gentamicin were determined by immunoassay on 1st and 5th day treatment. Thereafter, elimination rate constants and corresponding half-lives were calculated. Results: No significant increase in SCR concentrations in both groups was observed, but values on day 7 were slightly above normal. Conversely, there was a significant increase above normal in serum urea nitrogen on days 4 and 7 in Group A, whereas this was observed only on day 7 in Group B. Even though all other biochemical parameters assayed for were within normal, an increasing trend was noticed as the length of treatment days increased in both groups. In both groups, peak serum concentrations of gentamicin did not differ significantly. There was a 4- and 16-fold significant increase in trough levels after the last treatment in Groups A and B, respectively. Although peak and trough concentrations increased with increasing length of treatment, all the values were well below 10 μg/ml and 2 μg/ml, respectively, as required. Conclusion: These suggest the risk of nephrotoxicity following treatment with gentamicin beyond 5 consecutive days irrespective of the dosing interval in puppies.