Evaluating the effect of crocin on contrast-induced nephropathy in rats

Abstract

Objective: Contrast-induced nephropathy (CIN) raises the risk of renal injury, but crocin, a saffron component, may improve kidney function. This study investigated crocin's protective effects against CIN in rats.

Materials and methods: Male Wistar rats were divided into eight groups: Sham, Control, Contrast medium (diatrizoate), Diatrizoate combined with crocin at 10, 20, or 40 mg/kg/day, Diatrizoate combined with N-acetylcysteine (NAC) at 125 mg/kg/day, and Crocin alone at 40 mg/kg/day. Water deprivation began on day 5 for 48 hr, except for the sham and crocin alone groups. Indomethacin and N(ω)-nitro-L-arginine methyl ester were administered after 40 hr of dehydration. Rats were sacrificed on the eighth day, and blood and kidney samples were collected.

Results: Diatrizoate increased serum creatinine and blood urea nitrogen levels, elevated malondialdehyde levels, and reduced glutathione in renal tissue. Crocin reversed these effects. Diatrizoate caused severe tubular necrosis, proteinaceous casts, medullary congestion, and interstitial edema in kidney tissue. Crocin (20 and 40 mg/kg) significantly reduced tubular necrosis, and doses of 10 and 40 mg/kg reduced interstitial edema. NAC significantly improved histopathological damage, biochemical factors, and oxidative stress. The crocin alone group showed no significant changes.

Conclusion: Diatrizoate induces nephrotoxicity by enhancing oxidative stress in rats, and crocin has a protective effect against it. Crocin mitigates both tissue and biochemical damage inflicted by diatrizoate.

Keywords: Antioxidants; Contrast medium; Diatrizoate; Indomethacin; L- NAME; Nephropathy.

Figure 1

Schematic diagram of the study protocol. IND: indomethacin, L- NAME: N(ω)-nitro-L-arginine methyl ester, CM: contrast medium, and NAC: N-acetylcysteine.

Figure 2

Effect of crocin and diatrizoate on A: BUN and B: serum creatinine levels. Contrast medium (12.5 mg/kg), crocin (10, 20, and 40 mg/kg), and NAC (125 mg/kg) were administered to rats. Data are Mean±SD (n=6). ANOVA test and Tukey-Kramer posttest were used to check the statistical difference. ###p<0.001 compared to sham group and ***p<0.001 compared to contrast medium group. CM: contrast medium, NAC: N-acetylcysteine.

Figure 3

Effect of crocin and diatrizoate on renal A: MDA and B: GSH levels. Contrast medium (12.5 mg/kg), crocin (10, 20, and 40 mg/kg), and NAC (125 mg/kg) were administered to rats. Data are Mean±SD (n=6). ANOVA test and Tukey-Kramer posttest were used to check the statistical difference. ###p<0.001 compared to sham group and ***p<0.001 compared to contrast medium group. CM: contrast medium, NAC: N-acetylcysteine.

Figure 4

Effect of crocin and diatrizoate on renal histology: A: tubular necrosis B: proteinaceous casts, C: medullary congestion, and D: interstitial edema. Contrast medium (12.5 mg/kg), crocin (10, 20, and 40 mg/kg), and NAC (125 mg/kg) were administered to rats. Data are median ± IQR (n=6). ANOVA test and non-parametric Kruskal-Wallis test were used to check the statistical difference. ###p<0.001, ##p<0.01, and #p<0.05 compared to sham group and ***p<0.001, **p<0.01, and *p<0.05 compared to contrast medium group. CM: contrast medium, and NAC: N-acetylcysteine.

Figure 5

Samples of tissue pathology images of different groups stained with hematoxylin and eosin (40_X magnification). A: Section of the sham group without histopathological damage. B: Section of contrast medium group with tubular necrosis and proteinaceous casts. C: Section of contrast medium group with proteinaceous casts. D: Section of contrast medium group with interstitial edema. E: Section of contrast medium+crocin 10 mg/kg group with proteinaceous casts. F: Section of crocin 40 mg/kg alone group without histopathological damage.