l-Arginine attenuates the ethylene glycol induced urolithiasis in ininephrectomized hypertensive rats: role of KIM-1, NGAL, and NOs

Figures & data

Table 1. Effect of l-arginine on body weight, urine output, water intake, urine density, relative organ weight, and urine pH in EG (ethylene glycol) induced urolithiasis in uninephrectomized rats.

Treatment	Body weight (gm)	Urine output (ml)	Water intake (ml)	Urine density (gm/ml)	Dry weight of urine (mg)	Urine pH	Heart/body weight	Kidney/body weight
N	262.65 ± 7.12	11.67 ± 0.33	53.00 ± 2.51	0.82 ± 0.031	7.83 ± 0.95	7.50 ± 0.29	0.31 ± 0.026	0.47 ± 0.012
UC	190.52 ± 6.52###	8.67 ± 0.33###	25.00 ± 1.52###	1.09 ± 0.014###	22.57 ± 1.24###	5.67 ± 0.34###	0.37 ± 0.021###	0.67 ± 0.024###
T (10)	250.66 ± 8.98***	11.33 ± 0.33***	57.33 ± 2.33***	0.89 ± 0.026***	8.53 ± 0.72***	8.34 ± 0.33***	0.33 ± 0.014***	0.58 ± 0.010*
C (500)	253.00 ± 11.11***	15.33 ± 1.76***	54.33 ± 2.72***	0.83 ± 0.014***	7.8 ± 1.04***	8.67 ± 0.33***	0.36 ± 0.017	0.47 ± 0.022***
LA (250)	230.68 ± 4.20*	9.33 ± 1.02*	29.52 ± 1.08*	0.87 ± 0.005	18.74 ± 0.21	5.78 ± 0.53	0.37 ± 0.019	0.68 ± 0.030*
LA (500)	248.78 ± 9.54**	10.11 ± 0.43**	38.65 ± 6.17**	0.92 ± 0.042**	12.20 ± 0.15**	6.03 ± 0.31**	0.37 ± 0.023	0.57 ± 0.024**
LA (1000)	259.10 ± 7.54***	10.87 ± 0.51***	48.20 ± 2.15***	0.95 ± 0.043***	8.12 ± 0.64***	7.21 ± 0.41***	0.32 ± 0.01***	0.53 ± 0.014***

Notes: Results are represented as mean ± SEM (n = 6) Data are analyzed by One-way ANOVA followed by post hoc Dunnett’s tests. ###p < 0.001 as compared with normal group. *p < 0.05, **p < 0.01, ***p < 0.001 as compared with the urolithiasis control (UC) group.

Table 2. Effects of l-arginine on electrocardiographic abnormalities in EG-induced urolithiasis in uninephrectomized rats.

Treatment	QRS interval (ms)	Heart rate (BPM)	QTc interval	ST height
N	13.79 ± 0.26	363.96 ± 15.23	108.84 ± 7.60	1.50 ± 0.33
UC	18.86 ± 0.78###	413.25 ± 8.94###	132.05 ± 4.04###	7.24 ± 0.56###
T (10)	13.47 ± 0.36***	374.05 ± 6.52***	120.00 ± 2.41	2.52 ± 0.56***
C (500)	14.79 ± 0.22**	383.93 ± 18.79***	138.28 ± 5.14	3.99 ± 0.46***
LA (250)	17.08 ± 0.41*	412.20 ± 11.20*	130.18 ± 8.12	5.42 ± 0.63*
LA (500)	15.48 ± 0.38**	381.22 ± 12.00**	129.22 ± 1.84	4.84 ± 0.11**
LA (1000)	14.22 ± 0.22***	371.55 ± 12.41***	129.42 ± 3.15	1.89 ± 0.48***

Notes: Results are represented as mean ± SEM (n = 6) Data are analyzed by One-way ANOVA followed by post hoc Dunnett’s tests. ###p < 0.001 as compared with normal group. *p < 0.05, **p < 0.01, ***p < 0.001 as compared with the urolithiasis control (UC) group.

Table 3. Effect of l-arginine on hemodynamic parameters in EG-induced urolithiasis in uninephrectomized rats.

Treatment	Systolic BP (mmHg)	Diastolic BP (mmHg)	MABP (mmHg)	LVEDP (mmHg)	LV Contractility Index (s^−1)	Max dp/dt (mmHg/s)	Min dp/dt (mmHg/s)
N	107.3 ± 7.31	74.01 ± 1.59	78.55 ± 2.38	2.48 ± 0.55	83.75 ± 3.89	3148 ± 180.7	−2332 ± 79.75
UC	127.3 ± 2.45###	85.95 ± 2.64###	94.35 ± 1.15###	7.45 ± 0.35###	67.35 ± 3.14###	4276 ± 161.3###	−3594 ± 86.03###
T (10)	113.6 ± 2.79***	76.98 ± 1.98***	69.15 ± 3.27***	3.20 ± 0.27***	79.89 ± 2.42***	3441 ± 247.6***	−2576 ± 52.35***
C (500)	118.4 ± 5.07**	78.03 ± 1.38**	87.64 ± 2.84*	5.48 ± 0.15**	69.60 ± 1.47	4197 ± 199.6	−3479 ± 24.59
LA (250)	128.0 ± 3.33	84.78 ± 3.01	93.55 ± 2.21	6.08 ± 0.20	68.44 ± 2.14	4251 ± 122.87	−3487 ± 144.2
LA (500)	117.5 ± 2.84**	80.10 ± 0.89**	87.92 ± 2.55**	5.84 ± 0.20**	75.22 ± 1.89**	3658 ± 178.55**	−2879 ± 142.9**
LA (1000)	111.40 ± 1.87***	74.44 ± 1.54***	81.22 ± 1.16***	3.41 ± 0.44***	79.11 ± 2.15***	2875 ± 145.6***	−2487 ± 98.78***

Notes: Results are represented as mean ± SEM (n = 6) Data are analyzed by One-way ANOVA followed by post hoc Dunnett’s tests. ###p < 0.001 as compared with normal group. *p < 0.05, **p < 0.01, ***p < 0.001 as compared with the urolithiasis control (UC) group.

Table 4. Effect of l-arginine on serum and urine biochemical parameters in EG-induced urolithiasis in uninephrectomized rats.

Treatment	BUN (mg/dL)	Uric Acid (mg/dL)	Creatinine (mg/dL)	Sodium (mg/g)	LDH (mg/dL)	Calcium (mg/g)	Citrate (mg/g)	Albumin (gm/dL)
N
Serum	3.08 ± 0.43	2.15 ± 0.07	0.184 ± 0.039	141.8 ± 2.54	1331 ± 82.95	19.92 ± 0.19	–	–
Urine	12.17 ± 1.63	1.87 ± 0.26	8.48 ± 1.39	443.2 ± 7.17	–	18.54 ± 1.09	3.97 ± 0.09	2.27 ± 0.30
UC
Serum	17.80 ± 2.43###	4.14 ± 0.20###	0.614 ± 0.043###	187.1 ± 1.89###	1985 ± 126.6###	27.59 ± 2.30###	–	–
Urine	66.5 ± 4.13###	4.22 ± 0.37###	43.27 ± 3.02###	332.4 ± 47.63###	–	34.37 ± 0.77###	2.03 ± 0.20###	0.53 ± 0.10###
T (10)
Serum	8.60 ± 1.74**	2.73 ± 0.20***	0.329 ± 0.034***	171.4 ± 3.99*	1608 ± 220.0*	22.97 ± 0.41***	–	–
Urine	20.42 ± 1.85***	2.09 ± 0.35***	19.44 ± 5.43***	348.3 ± 33.01	–	24.18 ± 0.30***	3.80 ± 0.21***	1.74 ± 0.07***
C (500)
Serum	8.43 ± 0.90***	2.71 ± 0.21***	0.399 ± 0.077**	155.2 ± 5.23***	1734 ± 79.55	19.31 ± 1.36***	–	–
Urine	16.06 ± 8.10***	1.68 ± 0.25***	20.18 ± 2.07***	381.9 ± 2.34***	–	19.70 ± 0.80***	3.64 ± 0.28***	1.20 ± 0.6**
LA (250)
Serum	16.77 ± 1.26	3.23 ± 0.53	0.486 ± 0.018	180.00 ± 3.66	2083 ± 226.8	29.52 ± 0.98	–	–
Urine	60.35 ± 2.62	3.98 ± 0.26	41.29 ± 4.21	358 ± 14.69	–	32.61 ± 11	2.11 ± 0.05	0.62 ± 0.01
LA (500)
Serum	9.14 ± 2.01**	2.93 ± 0.42**	0.380 ± 0.061**	165.2 ± 1.04**	1520 ± 140.5**	24.99 ± 1.16**	–	–
Urine	47.92 ± 1.15**	2.50 ± 0.24***	22.29 ± 1.48**	414.9 ± 19.93**	–	27.94 ± 0.36**	3.34 ± 0.02***	1.35 ± 0.09**
LA (1000)
Serum	2.98 ± 0.56***	2.73 ± 0.21***	0.266 ± 0.104***	149.9 ± 1.58***	1216 ± 66.03***	15.92 ± 0.49***	–	–
Urine	2.17 ± 0.17***	1.37 ± 0.07***	20.61 ± 3.83***	449.3 ± 9.54***	–	20.92 ± 0.09***	3.76 ± 0.03***	1.97 ± 0.14***

Notes: Results are represented as mean ± SEM (n = 6) Data are analyzed by One-way ANOVA followed by post hoc Dunnett’s tests. ###p < 0.001 as compared with normal group. *p < 0.05, **p < 0.01, ***p < 0.001 as compared with the urolithiasis control (UC) group.

Figure 1. Effect of l-arginine on cardiac and renal SOD, GSH, MDA, and NO in EG-induced urolithiasis in uninephrectomized rats. Results are represented as mean ± SEM (n = 6) Data are analyzed by One-way ANOVA followed by post hoc Dunnett’s tests. ###p < 0.001 as compared with normal group. *p < 0.05, **p < 0.01, ***p < 0.001 as compared with urolithiasis control group.

Figure 2. Effect of l-arginine on renal KIM-1, NGAL, eNOs, and iNOs mRNA expression in EG-induced urolithiasis in uninephrectomized rats (A), quantitative representation of mRNA expression of KIM-1 (B), NGAL (C), eNOs (D), and iNOs (E). Results are represented as mean ± SEM (n = 4) Data are analyzed by One-way ANOVA followed by post hoc Dunnett’s tests. ###p < 0.001 as compared with normal group. *p < 0.05, **p < 0.01 as compared with urolithiasis control group.

Figure 3. Effect of l-arginine on alteration in kidney histology in EG-induced urolithiasis in uninephrectomized rats. Photomicrograph of sections of kidney of normal (A), urolithiasis control rats (B), Telmisartan (10 mg/kg) treated rats (C), Cystone (500 mg/kg) treated rats (D), l-arginine (500 mg/kg) treated rats (E), and l-arginine (1000 mg/kg)-treated rats (F). H & E staining at 100 × .

Figure 4. Effect of l-arginine on alteration in heart histology in EG-induced urolithiasis in uninephrectomized rats. Photomicrograph of sections of heart of normal (A), urolithiasis control rats (B), Telmisartan (10 mg/kg) treated rats (C), Cystone (500 mg/kg) treated rats (D), l-arginine (500 mg/kg treated rats (E), and l-arginine (1000 mg/kg) treated rats (F). H & E staining at 100×.

Charles L, Smith M, Guay D. Nephrolithiasis Pharmacotherapy – A Pathophysiological Approach. 3rd ed. Appleton and Langue 1999;1033–1036

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