Evaluation of the protective effect of paricalcitol and vitamin D₃ at doxorubicin nephrotoxicity in rats with ^99mTechnetium-dimercaptosuccinic acid renal scintigraphy and biochemical methods

Abstract

Aim: The present study aimed to examine the effect of paricalcitol (PRC) and vitamin D3 (vit D3) on doxorubicin (DOX)-induced nephrotoxicity in rats. Materials and Methods: Forty-two Wistar rats were randomly categorized into six groups: control; 2) PRC(0.5 µg/kg) and 3) vit D3(5.000 IU/kg) administered for 14 days; 4) DOX, 18 mg/kg administered on the 12th, 13th and 14th days of the study; 5) PRC (0.5 µg/kg, +DOX(18 mg/kg); vit D3(5.000 IU)+DOX(18 mg/kg). On the 15th day of the experiment, 99mTc-DMSA uptake level and biochemical parameter in serum and tissue were assay. Results: Activities of 99mTechnetium-Dimercaptosuccinic Acid (99mTc-DMSA) were lower in groups receiving DOX and/or PRC+DOX, vit D3+DOX than in control groups. The 99mTc-DMSA level in the group PRC+DOX and vit D3+DOX were importantly higher than DOX group. DOX caused an important increase in blood urea nitrogen (BUN), creatinine, Tumor Necrosis Factor-α(TNF- α), interleukin-6(IL-6) and nitric oxide(NO) levels compared to control groups. However, PRC and vit D3 pretreatments lowered them. Uptake of 99mTc-DMSA level was higher in groups PRC+DOX than in vit D3+DOX group. Administration of PRC and vit D3 alone did not change alterations all of parameters. Conclusion: The results indicated that PRC administration protects kidney in DOX-induced nephrotoxic rats. In addition, PRC has a stronger nephroprotective effect than vit D3.

Anti-inflammatory effects of saxagliptin and vildagliptin against doxorubicin-induced nephrotoxicity in rats

“…In the current work, DXR resulted in significant deterioration of renal functions as manifested by elevation of serum creatinine and BUN concentrations as compared to the normal control group. These data are in accordance with previous studies ( 9 13 17 ). Our results also demonstrated that DXR administration led to a significant increment in renal tissue concentration of inflammatory markers; TNF-α and IL-1β in comparison to the normal control group.…”

“…Renal tubular injury is accompanied by the rise of neutrophil gelatinase-associated lipocalin (NGAL) concentrations ( 12 ). Therefore, it has been crucial to scout for new therapeutic agents that can decrease DXR-induced nephrotoxicity to enhance its clinical use ( 13 ).…”

Paricalcitol Improves the Angiopoietin/Tie-2 and VEGF/VEGFR2 Signaling Pathways in Adriamycin-Induced Nephropathy

“…In the ADR model, there are alterations in the NO pathways, probably due to endotheliotoxicity, inhibiting and uncoupling eNOS, preventing its phosphorylation and NO availability [13,48]. Paricalcitol is involved in regulatory mechanisms in NO pathways preventing reactive oxygen species (ROS) production and free radicals [14,17]. Vit.…”

“…Paricalcitol (19-nor-1,25-hydroxyvitamin D2), an analog of calcitriol, and vit. D receptor activators (VDRA) can prevent parathyroid hormone (PTH) secretion and secondary hyperparathyroidism (SHPT) in CKD [17]. Many clinical studies have shown the effects of paricalcitol therapy to attenuate CKD, indicated by efficiency and safety in PTH levels and calcium-phosphorus regulation, and in the reduction in the proteinuria progression when associated with renin-angiotensin system (RAS) blocker in a non-SHPT CKD [18].…”