p-Coumaric acid, a common dietary polyphenol, protects cadmium chloride-induced nephrotoxicity in rats

Figures & data

Table 1. Effect of p-coumaric acid on serum kidney markers in cadmium chloride-intoxicated rats.

Parameter (mg/dl)	Group I Control	Group II Cadmium chloride	Group III Cadmium chloride + p-coumaric acid	Group IV Cadmium chloride + Silymarin
Urea	11.02 ± 0.41	24.07 ± 0.40^a*	14.99 ± 0.45^a*^b*	14.81 ± 0.43^a*^c*
Uric acid	1.07 ± 0.28	2.15 ± 0.26^a*	1.38 ± 0.10^a*^b*	1.25 ± 0.25^a*^c*
Creatinine	0.64 ± 0.02	2.75 ± 0.07^a*	0.90 ± 0.22^a*^b*	1.13 ± 0.18^a*^c*

Notes: Each value represents the mean ± SD of six rats. Comparisons were made as follows: ^aGroup I versus Group II, III and IV, ^bGroup II versus Group III, ^cGroup II versus Group IV. Statistical analysis was calculated by one-way ANOVA followed by Student’s Newman–Keul’s test.

*Statistical significance at p < 0.05.

Table 2. Effect of p-coumaric acid on urinary kidney markers in cadmium chloride-intoxicated rats.

Parameter (mg/day)	Group I Control	Group II Cadmium chloride	Group III Cadmium chloride + p-coumaric acid	Group IV Cadmium chloride + Silymarin
Urea	46.83 ± 2.39	27.38 ± 2.06^a*	43.20 ± 2.11^a*^b*	42.38 ± 1.63^a*^c*
Uric acid	342.83 ± 2.06	175.45 ± 2.06^a*	320.31 ± 1.76^a*^b*	318.37 ± 0.03^a*^c*
Creatinine	25.59 ± 1.38	8.70 ± 0.78^a*	24.61 ± 0.89^b*	24.76 ± 1.12^c*

Notes: Each value represents the mean ± SD of six rats. Comparisons were made as follows: ^aGroup I versus Group II, III and IV, ^bGroup II versus Group III, ^cGroup II versus Group IV. Statistical analysis was calculated by one-way ANOVA followed by Student’s Newman–Keul’s test.

*Statistical significance at p < 0.05.

Table 3. Effect of p-coumaric acid on kidney lipid peroxidation levels and antioxidant status in cadmium chloride-intoxicated rats.

Parameter	Group I Control	Group II Cadmium chloride	Group III Cadmium chloride + p-coumaric acid	Group-IV Cadmium chloride + Silymarin
Lipid peroxidation (LPO)	1.75 ± 0.03	4.73 ± 0.04^a*	1.88 ± 0.04^b*	1.93 ± 0.07^a*^c*
Superoxide dismutase (SOD)	13.13 ± 0.71	5.70 ± 0.18^a*	10.53 ± 0.31^a*^b*	9.73 ± 0.19^a*^c*
Catalase (CAT)	53.31 ± 2.02	29.99 ± 3.68^a*	44.64 ± 1.01^a*^b*	46.08 ± 1.59^a*^c*
Glutathione peroxidase (GPx)	4.52 ± 0.17	1.86 ± 0.52^a*	3.67 ± 0.30^a*^b*	3.81 ± 0.26^a*^c*
Glutathione reductase (GR)	0.27 ± 0.01	0.13 ± 0.02^a*	0.21 ± 0.02^a*^b*	0.22 ± 0.01^a*^c*
Glutathione-s-transferase (GST)	4.94 ± 0.02	2.16 ± 0.01^a*	3.91 ± 0.04^a*^b*	3.85 ± 0.14^a*^c*
Total reduced glutathione (GSH)	5.50 ± 0.10	2.64 ± 0.10^a*	4.74 ± 0.39^a*^b*	4.75 ± 0.36^a*^c*

Notes: Each value represents the mean ± SD of six rats. Comparisons were made as follows: ^aGroup I versus Group II, III, IV; ^bGroup II versus Group III; ^cGroup II versus Group IV. Statistical analysis was calculated by one-way ANOVA followed by Student’s Newman–Keul’s test. Units: LPO: nmol of MDA formed/mg protein; CAT: μmol of H₂O₂ consumed/min/mg protein; SOD: units/mg protein (1 U = amount of enzyme that inhibits the autooxidation of pyrogallol by 50%); GPx: μg of GSH utilized/min/mg protein; GR: nmol of NADPH oxidized/min/mg protein; GST: nmol of 1-chloro-2,4-dinitrobenzene–GSH conjugate formed/min/mg protein; Total reduced glutathione-nmol/mg/protein.

*Statistical significance at p < 0.05.

Table 4. Effect of p-coumaric acid on lysosomal enzymes in kidney of cadmium chloride-intoxicated rats.

Parameters	Group-I Control	Group-II Cadmium chloride	Group-III Cadmium chloride + p-coumaric acid	Group-IV Cadmium chloride + Silymarin
Acid phosphatase	4.70 ± 0.19	15.12 ± 0.42^a*	6.58 ± 0.16^a*^b*	6.82 ± 0.10^a*^c*
N-acetyl glucosaminidase	46.55 ± 0.71	72.42 ± 0.85^a*	55.84 ± 1.23^a*^b*	52.67 ± 2.19^a*^c*
β-galactosidase	35.03 ± 1.89	75.36 ± 0.69^a*	46.26 ± 0.79^a*^b*	48.10 ± 1.05^a*^c*
Cathepsin-d	8.04 ± 0.45	18.28 ± 1.08^a*	10.28 ± 0.51^a*^b*	11.07 ± 0.41^a*^c*

Notes: Each value represents the mean ± SD of six rats.

Comparisons were made as follows: ^aGroup I versus Group II, III, and IV, ^bGroup II versus Group III and ^cGroup II versus Group IV. Statistical analysis was calculated by one-way ANOVA followed by Student’s Newman–Keul’s test. Units: Acid phosphatase – μmol phenol liberated/min/mg/protein; N-acetyl glucosaminidase and β-galactosidase – μmol p-nitrophenol formed/h/mg protein; cathepsin D – μmol of tyrosine liberated/h/mg of protein.

*Statistical significance at p < 0.05.

Table 5. Effect of p-coumaric acid on glycoproteins in kidney of cadmium chloride-intoxicated rats.

Parameters (mg/g defatted tissue)	Group-I Control	Group-II Cadmium chloride	Group-III Cadmium chloride + p-coumaric acid	Group-IV Cadmium chloride + Silymarin
Sialic acid	4.91 ± 0.38	14.55 ± 0.63^a*	7.74 ± 0.15^a*^b*	7.13 ± 0.36^a*^c*
Hexosamine	7.16 ± 0.15	18.19 ± 0.30^a*	10.13 ± 0.28^a*^b*	10.20 ± 0.28^a*^c*

Notes: Each value represents the mean ± SD of six rats. Comparisons were made as follows: ^aGroup I versus Group II, III, and IV, ^bGroup II versus Group III and ^cGroup II versus Group IV. Statistical analysis was calculated by one-way ANOVA followed by Student’s Newman–Keul’s test.

*Statistical significance at p < 0.05.

Figure 1. Effect of p-coumaric acid on metallothionein concentration in kidney tissues of rats exposed to cadmium chloride. Group I – Control rats, Group II – Cadmium chloride-intoxicated rats, Group III – Cadmium chloride-intoxicated rats treated with p-coumaric acid (100 mg/kg b.wt) and Group IV – Cadmium chloride-intoxicated rats treated with Silymarin (50 mg/kg b.wt). Each value represents the mean ± SD of six rats. Comparisons were made as follows: ^aGroup I versus Group II, III and IV, ^bGroup II versus Group III and ^cGroup II versus Group IV. The symbols represent statistical significance at: *p < 0.05. Statistical analysis was calculated by one-way ANOVA followed by Student’s Newman–Keul’s test.

Figure 2. Effect of p-coumaric acid on cadmium concentration in kidney tissues of rats exposed to cadmium chloride. Group I – Control rats, Group II – Cadmium chloride-intoxicated rats, Group III – Cadmium chloride-intoxicated rats treated with p-coumaric acid (100 mg/kg b.wt) and Group IV – Cadmium chloride-intoxicated rats treated with Silymarin (50 mg/kg b.wt). Each value represents the mean ± SD of six rats. Comparisons were made as follows: ^aGroup I versus Group II, III and IV, ^bGroup II versus Group III and ^cGroup II versus Group IV. The symbols represent statistical significance at: *p < 0.05. Statistical analysis was calculated by one-way ANOVA followed by Student’s Newman–Keul’s test.

Figure 3. Histopathological analysis of the nephroprotective potential of p-coumaric acid in cadmium chloride-intoxicated rats (H&E 20X). (a) Control rats showing normal rat kidey – normal glomeruli and tubular structure. (b) Cadmium chloride-intoxicated rats showing severe kidney tubular epithelial cell degeneration. (c,d) Cadmium chloride followed by p-coumaric acid (100 mg/kg b.wt) and silymarin (50 mg/kg b.wt) treated rats, respectively, showing improvement over cadmium intoxicated group with mild tubular epithelial cell degeneration.