Transdermal Drug Delivery of Asiatic Acid Influences Renal Function and Electrolyte Handling in Plasmodium berghei - Infected Sprague-Dawley Male Rats

摘要

Background: Malaria is one of the most important infectious inflammatory diseases worldwide which affects vital organs including gastrointestinal and kidneys. Higher prevalence of malaria related renal failure, current malaria drugs nephrotoxicity and drug resistance to malaria calls for continued research in anti-parasitic as well as anti-disease inflammatory pharmaceuticals. Asiatic acid, a plant phytochemical extract, has antioxidant, pro-oxidant and diuretic properties. Here we report influence of Asiatic acid-pectin hydrogel matrix patch application in P. berghei-infected Sprague Dawley rats on renal function and electrolyte handling. Materials and Methods: Asiatic acid (5mg/kg)-pectin patch was applied on the dorsal neck region of the rat on day 7 post infection and monitored for parasitaemia, and physicochemical changes. Urine and blood were collected for measuring various biochemical parameters to estimate renal function and electrolyte handling. Results: Asiatic acid-pectin patch application had significant influence on food and water intake as well as weight changes, urine electrolytes, glomerular filtration rate, and antioxidant markers together with hormonal changes of aldosterone and vasopressin. Conclusion: Application of the once-off Asiatic acid (5mg/kg)-pectin patch influence renal function and renal electrolyte handling while ameliorating, biochemical and hormonal derangements induced by malaria. Novelty of the Work Here we show for the first time a) the efficacy of Asiatic acid (AA) in suppressing murine malaria by way of administering the phytochemical using the amidated pectin hydrogel matrix patch transdermal drug delivery system, b) diminution of asiatic acid dose applied from 10mg/kg oral to 5mg/kg by transdermal, c) reduction of time once-off patch application from five days to three days, d) attenuation of oxidative and hormonal derangements in malaria and e) the amelioration of renal function together with improvement in renal electrolyte handling. The results may be of benefit in patient care replacing the multiple dosing approaches used in malaria management.