Abstract
BackgroundCyclosporine A (CsA) is an immunosuppression agent used frequently in fields of organs transplantation and autoimmune diseases. However, CsA-induced kidney injury is a major clinical problem associated with CsA therapy in which the conceivable accountable mechanism is oxidative stress (OS). The present study evaluated the protective and ameliorated effects of fucoidan (FU) as an antioxidant and an anti-inflammatory agent against CsA-induced kidney injury.MethodsMale rats were randomly divided into three groups. The first group was served as a control group that administered olive oil orally and normal saline subcutaneously, the second group (CA) was treated with CsA orally, and the third group (CA + FU) was treated with CsA orally in concomitant with FU subcutaneously. Experimental animals were sacrificed 20 days following the treatment period and serum samples were analyzed for creatinine test. The homogenate of renal tissues was prepared for OS assessment. Light and ultrastructure microscopic kidney sections were prepared for histopathological examination.ResultsTreatment of rats with CsA alone produced a significant increase in the levels of creatinine, nitric oxide (NO), and malondialdehyde (MDA), as well as the activities of superoxide dismutase (SOD), catalase (CAT), and glucose 6 phosphate dehydrogenase (G6PD), whereas the level of glutathione reduced (GSH) was decreased. Some histopathological changes of the kidney tissue including tubular epithelial hypertrophy, vacuolizations, necrotic glomerulus cell, capillaries network shrinking, vascular congestion, interstitial infiltration, loss of apical microvilli, and deteriorated mitochondria were observed in CA group. Concomitant FU administration with CsA enhanced renal function, as indicated by the low level of creatinine. Moreover, FU ameliorated the oxidative status in kidney tissue as well as it provided histological protection against CsA-induced kidney injury.ConclusionFU can develop a protective mechanism against kidney injury induced by CsA that mediated by OS.
Highlights
Cyclosporine A (CsA) is an immunosuppression agent used frequently in fields of organs transplantation and autoimmune diseases
Biochemical estimations result Serum creatinine level Cyclosporine A-induced kidney injury in experimental rats that was demonstrated by a significant elevation of serum creatinine level when compared with that in the control group (p < 0.001) as shown in Fig. 1, whereas FU concomitant treatment with CsA caused a significant decrease in this level as compared to CA group (p < 0.01)
Both CsA treatment alone and CsA with FU treatment caused high increased in nitric oxide (NO) level of kidney tissue when compared to the control group (p < 0.001) with a higher percentage of NO production in CA group compared to CA + FU group (155.172 and 120.689, respectively)
Summary
Cyclosporine A (CsA) is an immunosuppression agent used frequently in fields of organs transplantation and autoimmune diseases. The present study evaluated the protective and ameliorated effects of fucoidan (FU) as an antioxidant and an anti-inflammatory agent against CsA-induced kidney injury. Cyclosporine A (CsA) is one of the calcineurin inhibitors that is widely used as immunosuppressive therapy in areas of organs transplantation and autoimmune diseases especially dermal diseases and inflammatory diseases such as rheumatoid arthritis, psoriasis, and atopic dermatitis (Harper, Berth-Jones, Camp, Dillon, Finlay, Holden, O’Sullivan, & Veys, 2001; Tedesco & Haragsim, 2012). Chronic nephrotoxicity is occurred in continued exposure to a lower level of CsA and does not recover after dose reduction (Slattery et al, 2005). The protective role of different antioxidants has been estimated on CsA-induced nephrotoxicity. The protecting role of antioxidants is confirmed on CsA hepatotoxicity (Rezzani, 2006)
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