Abstract
Previous studies reported the oral administration of Naja naja atra venom (NNAV) reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight) via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180 μg/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.
Highlights
Chronic kidney disease is characterized by reduced glomerular filtration and persistent massive proteinuria
Cardiotoxin significantly decreased the kidney coefficients at doses of 45, 90, and 180 μg/kg, respectively (P < 0.001, P < 0.01, and P < 0.001). These results demonstrated that intragastric administration of cardiotoxin can reduce loss of body weight and significantly ameliorate kidney hypertrophy in the rat chronic kidney disease model
The protein output was 502.46 ± 123.07 (P < 0.05, compared with the model group), 414.76 ± 106.98 (P < 0.001), 471.79 ± 94.70 mg/24 hours (P < 0.01) after administration of cardiotoxin at doses of 45, 90, and 180 μg/kg for 21 days, respectively. These results demonstrated that intragastric administration of cardiotoxin can significantly reduce proteinuria in a rat model of chronic kidney disease in the early stages
Summary
Chronic kidney disease is characterized by reduced glomerular filtration and persistent massive proteinuria. Because of its increasing morbidity and mortality, chronic kidney disease has become an important research field [1]. Glomerular filtration barrier damage plays a critical role in proteinuria in chronic kidney disease [3], which contains fenestrated endothelium, glomerular basement membrane (GBM), and slit diaphragm (SD) [4]. SD is the most important component of the glomerular filtration barrier. Previous studies have shown that podocin encoded by NPHS2 [5] is a critical component protein in slit diaphragm [6, 7], and that reduced expression of podocin correlates to the severity of proteinuria [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
