Naja Naja Atra Venom And Cobrotoxin Ameliorate Acute And Chronic Nephropathy Through Inhibiting Inflammation

Objectives: Acute and chronic nephropathy becomes global health problems with high morbidity and mortality. This study investigated the protective effects of Naja naja atra venom(NNAV) and its component cobrotoxin(CTX) on acute and chronic nephropathy in rats.Methods: Rats were received 8ml/kg 50% v/v glycerol to produce acute renal failure(ARF) or 6mg/kg adriamycin(ADR) once to evoke the chronic nephropathy. The NNAV was given orally once a day starting five days prior to glycerol or ADR and continued to the end of experiments. CTX was administered to rats daily by placing a fast dissolving CTX membrane strip under the tongue starting from five days prior to ADR administration until the end of experiment. The animals were placed in metabolic cages for 24 h for urine collection for urinary protein output analysis. The kidney function related biochemical changes and index of oxidative stress were determined with automatic biochemistry analyzer or colorimetric enzyme assay kits. The pathomorphological changes were observed using light and transmission electron microcopies. The levels of inflammatory cytokines, NF-κB activation, TGF-β and nephrin were determined using ELISA kits, Western blot analysis, or immunofluorescence.Results: The results showed that NNAV relieved glycerol-triggered acute renal failure and ADR-induced chronic nephropathy syndromes including proteinuria, hypoalbuminemia, hyperlipidemia, serum electrolyte unbalance, renal oxidative stress, and pathological damages. NNAV reduced kidney levels of TNF-? and IL-1β, but it increased the levels of I?B-? and inhibited NF-?B p65 nuclear localization. Meanwhile, CTX ameliorated the symptoms of ADR nephropathy syndrome with reduced body weight loss, dyslipidemia, serum electrolyte imbalance, oxidative stress, renal function abnormities, and kidney pathological lesions. Anti-inflammatory cytokine IL-10 expression was elevated after CTX administration in ADR nephropathy model. CTX inhibited the phosphorylation of I?B-? and NF-?B p65 nuclear translocation. CTX slightly upregulated the protein level of podocyte-specific nephrin and downregulated the level of fibrosis-related TGF-β.Conclusions: The present study revealed that NNAV and CTX had protective effects on acute and chronic nephropathy through inhibiting inflammatory responses. These findings suggest that NNAV and CTX may be valuable therapeutic drugs for acute and chronic kidney diseases.