The Nephroprotective Activity of Boesenbergia Rotunda Rhizome by Reducing Creatinine, Urea Nitrogen, Glutamic Pyruvic Transaminase, and Malondialdehyde Levels in the Blood and Attenuating the Expression of Havcr1 (KIM-1), Lcn2 (NGAL), Casp3, and Casp7 Genes in the Kidney Cortex of Cisplatin-Induced Sprague-Dawley Rats

Figures & data

Table 1 Effect of EEBR on the BW of the Rats Before and After Cisplatin-Induced Nephrotoxicity

Animal Groups	Body Weight (g) + SD
	Day 0 (Initial Body Weight)	Day 5 (Before Cisplatin Induction)	Day 10 (After Cisplatin induction)
Normal Control	161.02 ± 27.81	164.31 ± 30.77^#	168.45 ± 30.27^#
Negative Control	144.94 ± 12.86	146.29 ± 13.09	130.45 ± 17.35
Positive Control	176.19 ± 18.95	177.32 ± 19.01*	167.42 ± 25.20*
EEBR 125 mg/kg BW	174.66 ± 20.58	176.43 ± 20.90	160.96 ± 21.66
EEBR 250 mg/kg BW	142.39 ± 14.15	143.98 ± 14.06	135.21 ± 15.19
EEBR 500 mg/kg BW	143.48 ± 8.56	146.14 ± 10.10	135.10 ± 12.84

Notes: Statistical analysis was done using IBM SPSS Statistics version 25.0 for Windows. *indicates a significant difference (p<0.05) compared to the negative control. #indicates a significant difference (p<0.05) compared to day 0 of the normal control.

Figure 1 Effect of EEBR on kidney function (left: SCr; right: BUN) of cisplatin-induced nephrotoxicity rats. Only the highest dose of EEBR (500 mg/kg BW) shows protection against nephrotoxicity as portrayed by a significant difference in SCr and BUN levels compared to the negative control. The # denotes the significant difference with the normal control (p<0.05). The * indicates a remarkable difference with the negative control (p<0.05).

Table 2 Effect of EEBR on the Kidney Relative Weight of the Cisplatin-Induced Rats

Animal Groups	Relative Weight of the Left Kidney (Mean + SD)	p	Relative Weight of the Right Kidney (Mean + SD)	p
Normal Control	0.372 ± 0.028	0.001*	0.372 ± 0.016	0.002*
Negative Control	0.556 ± 0.021	--	0.540 ± 0.055	--
Positive Control	0.429 ± 0.093	0.005*	0.42 7± 0.068	0.004*
EEBR 125 mg/kg BW	0.446 ± 0.039	0.221	0.462 ± 0.043	0.194
EEBR 250 mg/kg BW	0.480 ± 0.054	0.146	0.459 ± 0.062	0.169
EEBR 500 mg/kg BW	0.435 ± 0.063	0.108	0.435 ± 0.033	0.108

Notes: Statistical analysis was done using IBM SPSS Statistics version 25.0 for Windows. *indicated a significant difference (p<0.05) compared to the negative control.

Figure 2 Effect of EEBR on liver function ((A). GPT; (B) GOT) of cisplatin-induced nephrotoxicity rats. All doses of EEBR improved GPT levels but not GOT levels of the cisplatin-induced nephrotoxicity rats. The highest dose of EEBR elevated the GOT levels of the cisplatin-induced nephrotoxicity rats. The # denotes the significant difference with the normal control (p<0.05). The * indicates a remarkable difference with the negative control (p<0.05).

Figure 3 Effect of EEBR on MDA level and viability of kidney cells in cisplatin-induced nephrotoxicity rats. The * indicates a remarkable difference with the negative control (p<0.05). The # indicates a remarkable difference from the normal control group (p<0.05). Histology of the kidney tissue of rats in (a) normal control; (b) negative control; (c) positive control; (d) EEBR 125 mg/kg BW; (e) EEBR 250 mg/kg BW; (f) EEBR 500 mg/kg BW. Red arrows show the Bowman capsule. Inflammatory cells are shown by black arrows.

Table 3 RT-PCR Analysis of Kim-1, NGAL, Casp-3, and Casp-7 Expression in the RNA Isolated from the Kidney Cortex of Cisplatin-Induced Sprague-Dawley Rats

Name of the Gene Expressed	Expression of Genes in RT-PCR Analysis (p-value Compared to the Negative Control)
	Normal Control	Positive Control	EEBR 125 mg/kg BW	EEBR 250 mg/kg BW	EEBR 500 mg/kg BW
Kim-1	0.558 (p = 0.000*)	0.624 (p = 0.002*)	0.729 (p = 0.040*)	0.647 (p = 0.003*)	0.602 (p = 0.001*)
NGAL	0.463 (p = 0.044*)	0.491 (p = 0.022*)	0.448 (p = 0.034*)	0.277 (p = 0.002*)	0.170 (p = 0.000*)
Casp-3	0.521 (p = 0.003*)	0.530 (p = 0.02*)	0.641 (p = 0.067)	0.561 (p = 0.022*)	0.510 (p = 0.001*)
Casp-7	0.486 (p = 0.004*)	1.560 (p = 0.971)	0.651 (p = 0.037*)	0.608 (p = 0.021*)	0.411 (p = 0.000*)

Notes: All values have been normalized against the housekeeping gene (β-actin). Statistical analysis was done using IBM SPSS Statistics version 25.0 for Windows. *Indicated a significant difference (p<0.05) compared to the negative control.

Table 4 Statistical Analysis of All Parameters

Group	Kidney Function		Liver Function		MDA in the Kidney Tissue	Total Number of Normal Cells
	BUN	sCr	GPT	GOT
Normal Control	0.000*	0.001*	0.003*	0.020*	0.000*	0.001*
Positive Control	0.000*	0.020*	0.004*	0.051	0.000*	0.039*
EEBR 125 mg/kg BW	0.998	0.400	0.011*	0.284	0.080	0.491
EEBR 250 mg/kg BW	0.000*	0.221	0.002*	0.126	0.013*	0.168
EEBR 500 mg/kg BW	0.000*	0.013*	0.025*	0.491	0.002*	0.006*
	ANOVA and post hoc Tukey’s test (p<0.05)	Kruskal–Wallis and Dunn’s test (p<0.05)	ANOVA and post hoc Tukey’s test (p<0.05)	Kruskal–Wallis and Dunn’s test (p<0.05)	ANOVA and post hoc Tukey’s test (p<0.05)	Kruskal–Wallis and Dunn’s test (p<0.05)

Notes: Statistical analysis was done using IBM SPSS Statistics version 25.0 for Windows. *Indicated a significant difference (p<0.05) compared to the negative control.

Data Sharing Statement

The data generated in the present study may be requested from the corresponding author upon reasonable request.