Protective Effect of Curcumin against Sodium Salicylate-Induced Oxidative Kidney Damage, Nuclear Factor-Kappa Dysregulation, and Apoptotic Consequences in Rats

Abstract

This study examined the effect of sodium salicylates (SS), alone and in combination with curcumin (CUR), on kidney function and architecture in rats. Five rat groups were given 1 mL physiological saline/rat orally, 1 mL olive oil/rat orally, 50 mg CUR/kg bwt orally, 300 mg SS/kg bwt intraperitoneally, or CUR+SS for 15 days. The hematological indices, serum protein profile, serum electrolytes balance, oxidative stress, and lipid peroxidation of kidney tissues were assessed. The histopathological examination and immune expression of Caspase-3 and nuclear factor kappa (NF-κB) were conducted. The findings showed that SS injection induced nephrotoxic activity, including increased serum urea, creatinine, and uric acid levels. It also caused apparent pathological alterations with increased Caspase-3 and NF-κB immuno-expression. In addition, thrombocytopenia, leukocytosis, neutrophilia, hyponatremia, hypochloremia, hypocalcemia, and hypomagnesemia but not hyperkalemia and hyperphosphatemia were evident in SS-injected rats. Moreover, SS exposure increased serum α1 globulin, renal tissue malondialdehyde, and Caspase-3 levels but superoxide dismutase, glutathione peroxidase, and Bcl-2 levels declined. Meanwhile, CUR significantly counteracted the SS harmful impacts on kidneys but SS+CUR co-administration induced an anemic condition. Overall, CUR has an evident protective role against SS-induced renal damage, but the disturbed hematological alterations should be carefully taken into consideration in their combined use.

Keywords: Caspase-3; NF-kappa B; anemia; curcumin; kidney; sodium salicylate.

Figure 1

Effect of curcumin (CUR) oral dose on (A) superoxide dismutase (SOD), (B) glutathione peroxidase (GPx), and (C) malondialdehyde (MDA) in the kidney tissues of sodium salicylate (SS)-injected rats for 15 days. C: control group. OO: olive oil. Data are expressed as mean ± SD, n = 10 for each group. * Significantly different compared to the control groups at p < 0.05. ^# Significantly different from the SS-treated group at p < 0.05.

Figure 2

Effect of curcumin (CUR) oral dose on Caspase-3 (A) and BCL-2 (B) in the kidney tissues of sodium salicylate (SS)-injected rats for 15 days. C: control group. OO: olive oil. Data are expressed as mean ± SD, n = 10 for each group. * Significantly different compared to the control groups at p < 0.05. ^# Significantly different from the SS-treated group at p < 0.05.

Figure 3

Photomicrograph of H&E-stained renal tissue sections. Control (C) and curcumin (CUR) group showing the normal glomeruli (G), renal tubules (arrows), outer layer of Bowman’s capsule (blue arrowhead), and capsular space (star). Sodium salicylate (SS)-treated group showing vascular congestion (arrowhead) and hyalinization of the blood vessel (zigzag arrow), absence of capsular space and glomerular congestion (G), coagulative necrosis (curved arrow), congestion of peritubular capillaries (arrowheads), absence of glomerular tuft (thick arrow), tubular dilation (circles) shrinkage of the glomerulus (triangle), and vacuolation of the lining epithelium of tubules (v). SS + CUR-treated group showing vascular congestion (arrowheads) and normal glomeruli (G). The magnification was ×400 in all photos, except the first one of SS was ×100.

Figure 4

Photomicrograph of the renal tissue sections showing the Caspase -3 immuno-expression in different studied groups: (C) control, (CUR) curcumin, (SS) sodium salicylate, and SS+CUR-treated groups. Magnification ×400.

Figure 5

Photomicrograph of the renal tissue sections showing the NF-κB immuno-expression in different studied groups: (C) control, (CUR) curcumin, (SS) sodium salicylate, and SS+CUR-treated groups. Magnification ×400.

Figure 6

Principal component analysis plot showing the relationships among the estimated variables. (A) Cumulative proportion of variance as a function of the number of principal components (PC). (B) All of the biochemical indicators plotted as a function of PC1 and PC2, which account for 82.48% and 6.04% of the variance, respectively. TB: total protein; TG: total globulin; ALB: albumin; Gpx: glutathione peroxidase; SOD: superoxide dismutase; and MDA: malondialdehyde.