Protective effect of curcumin against cyclosporine A‑induced rat nephrotoxicity

Abstract

This study explored the potential value of curcumin, a natural product, in the protection of CsA‑induced nephrotoxicity. The aim of the present study was to investigate the effects of curcumin on Cyclosporine A (CsA)‑induced renal oxidative stress and determine the potential underlying molecular mechanisms of the renal protective effects of Cur. HK‑2 human renal cells were co‑treated with CsA and various doses of Cur. Cell survival rate was determined by an MTT assay, total cellular protein was collected and oxidative stress in cell homogenates was evaluated by determining the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px) and catalase (CAT), the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), and total antioxidant capacity. Furthermore, Bcl‑2 and Bcl‑2‑associated X (Bax) protein expression was measured by western blot analysis. In addition, a CsA‑induced nephrotoxicity (CAN) rat model was also established. Renal function was analyzed by measuring creatinine (Crea) and blood urea nitrogen (BUN) in the serum of rats, and histopathological examination was performed on renal tissues using hematoxylin and eosin staining, periodic acid‑Schiff staining and nuclear factor‑κB (NF‑κB) immunostaining. The results demonstrated that treatment of HK‑2 cells with CsA significantly increased ROS and MDA levels, and decreased the activities of SOD, GSH‑Px and CAT, compared with the control group. However, these effects of CsA were dose‑dependently improved by treatment with Cur. In addition, Cur treatment increased Bcl‑2 and decreased Bax protein in HK‑2 cells, compared with cells treated with CsA alone. In the CAN rat model CsA (30 mg/kg) treatment significantly elevated serum Crea levels and BUN, but lowered endogenous Crea clearance rate, compared with the control group. Co‑administration of Cur with CsA significantly reversed the effects of CsA on serum Crea levels, BUN and Crea clearance rate (Ccr). Additionally, Cur alleviated CsA‑induced renal cell injury, as less vacuolar degeneration of glomerular cells was observed compared with the CsA alone group. In conclusion, Cur may increase renal antioxidant capacity and reduce the Bax/Bcl‑2 ratio, subsequently improving CsA‑induced renal failure and renal tubular deformation and cell vacuolization.

Bombyx mori gloverin A2 alleviates enterotoxigenic Escherichia coli-induced inflammation and intestinal mucosa disruption

“…In this study, ETEC challenge increased the fecal score (marking of the diarrhea) and impaired the spleen tissues. Moreover, the elevated serum concentrations of urea and crea indicated disruption of the kidney function in mice upon ETEC challenge [35,36]. The elevated serum concentrations of IL-6 and TNF-α indicating an acute inflammatory response in mice upon ETEC challenge.…”

Metformin and silymarin afford protection in cyclosporine A induced hepatorenal toxicity in rat by modulating redox status and inflammation

“…[ 7–9 ] The role of inflammation and altered oxidative homeostasis in the pathogenesis of CsA induced organ dysfunction is further strengthened by the studies carried out in experimental models where agents exhibiting antioxidant and antiinflammatory properties have been shown to afford protection against such damage. [ 8,10–13 ]…”

The therapeutic effects of curcumin and capsaicin against cyclophosphamide side effects on the uterus in rats

“…In vitro studies examining the antioxidant effect of CRC showed promising results. An in vitro rat study demonstrated that renal toxicity due to cyclosporine decreased significantly by CRC administration and TOS and MDA levels in this group were significantly low 17 . Another animal study detected that in renal tissues of cisplatin and methotrexate administered rats MDA level was increased and GSH level was decreased; however in CRC administered rats level of oxidant MDA significantly decreased and level of antioxidant GSH significantly increased 18 .…”