Weekly administration of betulinic acid prevents development of chronic renal failure from acute renal failure in folic acid-induced mouse model of kidney injury.

Betulinic acid (BA) has been shown to exhibit various pharmacological activities and it has shown the protective effect on acute renal failure (ARF) and chronic renal failure (CRF); however, no reports are available on its effect on ARF-CRF transition. Therefore, we aimed to investigate the effects of BA on ARF-CRF transition. A single dose of 250 mg/kg body weight (BW) intraperitoneal injection of folic acid was given in mice for inducing ARF-CRF transition (injury group; I) on day 1. Further, excess of these mice received BA at 30 mg/kg BW dose for 3 days (on days 1, 2, 3) in one group (IT3) and for 7 days (on days 1, 2, 3, 7, 14, 21, 28) in another group (IT7). All mice were sacrificed on day 28. Mice in injury group (I) showed elevated serum creatinine along with oxidative stress markers like urine nitrite, tissue lipid peroxidation, nitrotyrosine and fibrotic markers such as tissue α-smooth muscle actin and matrix metalloproteinase-2 activity. They had attenuated levels of urine creatinine and tissue reparative cytokines viz. interleukin-4 and interleukin-13. Excess of fibroblasts and extracellular matrix in the interstitia and periglomerular area in microscopy further support these findings. Seven days of BA treatment regimen (IT7) significantly improved serum and urine parameters accompanied by reduced oxidative stress, improved reparative cytokines and lesser maladaptive matrix deposition. The above findings reveal that weekly BA treatment regimen has potential to prevent development of CRF after ARF.