Nephroprotective effect of saxagliptin against gentamicin-induced nephrotoxicity, emphasis on anti-oxidant, anti-inflammatory and anti-apoptic effects.

Nephrotoxicity is a serious adverse effect frequently encountered with aminoglycosides administration. Given the value of aminoglycosides in management of serious infections, nephro-protection is highly recommended. The current study investigated the nephro-protective effect of saxagliptin (SAXA) (12.5 mg/kg, I.P.) against gentamicin (GEN)-induced nephrotoxicity in rats. SAXA administration for 14 days conferred significant nephro-protection against GEN-induced nephrotoxicity manifested in decreased kidney/somatic index, enhanced cytoprotection and significant decrease in serum LDH activity together with functional renal improvement; significant increase in creatinine clearance with significant reduction in serum creatinine, BUN, proteinuria and albuminuria. Oxidant/antioxidants hemostasis was significantly improved with SAXA treatment with significant reduction in kidney MDA content and enhancement of GSH concentration and catalase activity. Moreover, kidney content of NO significantly declined with significant decline in kidney tumor necrosis factorα (TNFα), vascular adhesion molecule-1 (VCAM-1) and caspase-3 content. Ultimately, SAXA administration was associated with significant attenuation of GEN-induced necrotic and inflammatory changes. In conclusion; the modulatory effect of SAXA on inflammatory cytokines, its anti-apoptic properties, ameliorative impact on oxidative load and positive impact on host antioxidant defenses accounts for the observed nephro-protective impact.

Tissue Regeneration and Stem Cell Distribution in Adriamycin Induced Glomerulopathy

BACKGROUND AND OBJECTIVES: Glomerulosclerosis develops secondary to various kidney diseases. It was postulated that adriamycin (ADR) induce chronic glomerulopathy. Treatment combinations for one year did not significantly modify renal function in resistant focal segmental glomerulosclerosis (FSGS). Recurrence of FSGS after renal transplantation impacts long-term graft survival and limits access to transplantation. The present study aimed at investigating the relation between the possible therapeutic effect of human mesenchymal stem cells (HMSCs), isolated from cord blood on glomerular damage and their distribution by using ADR induced nephrotoxicity as a model in albino rat. METHODS AND RESULTS: Thirty three male albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg adriamycin. The rats were sacrificed 10, 20 and 30 days following confirmation of glomerular injury. In stem cell therapy group, rats were injected with HMSCs following confirmation of renal injury and sacrificed 10, 20 and 30 days after HMSCs therapy. Kidney sections were exposed to histological, histochemical, immunohistochemical, morphometric and serological studies. In response to SC therapy multiple Malpighian corpuscles (MC) appeared with patent Bowman's space (Bs) 10 and 20 days following therapy. One month following therapy no remarkable shrunken glomeruli were evident. Glomerular area and serum creatinine were significantly different in ADR group in comparison to control and SC therapy groups. CONCLUSIONS: ADR induced glomerulosclerosis regressed in response to cord blood HMSC therapy. A reciprocal relation was recorded between the extent of renal regeneration and the distribution of undifferentiated mesenchymal stem cells.

Effect of Stem Cell Therapy on Adriamycin Induced Tubulointerstitial Injury

BACKGROUND AND OBJECTIVES: It was postulated that adriamycin (ADR) induce renal tubulointerstitial injury. Clinicians are faced with a challenge in producing response in renal patients and slowing or halting the evolution towards kidney failure. The present study aimed at investigating the relation between the possible therapeutic effect of human mesenchymal stem cells (HMSCs), isolated from cord blood on tubular renal damage and their distribution by using ADR induced nephrotoxicity as a model in albino rat. METHODS AND RESULTS: Thirty three male albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg adriamycin. The rats were sacrificed 10, 20 and 30 days following confirmation of tubular injury. In stem cell therapy group, rats were injected with HMSCs following confirmation of renal injury and sacrificed 10, 20 and 30 days after HMSCs therapy. Kidney sections were exposed to histological, histochemical, immunohistochemical, morphometric and serological studies. In response to SC therapy, vacuolated cytoplasm, dark nuclei, detached epithelial lining and desquamated nuclei were noticed in few collecting tubules (CT). 10, 20 and 30 days following therapy. The mean count of CT showing desquamated nuclei and mean value of serum creatinine revealed significant difference in ADR group. The mean area% of Prussian blue+ve cells and that of CD105 +ve cells measured in subgroup S1 denoted a significant increase compared to subgroups S2 and S3. CONCLUSIONS: ADR induced tubulointerstitial damage that regressed in response to cord blood HMSC therapy.