Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction

Figures & data

Table 1. Effect of berberine on GM-induced alterations in relative kidney weight, serum creatinine, BUN, and creatinine clearance in rats.

Parameters	Normal	GM-control	GM + BER (10)	GM + BER (20)	GM + BER (40)	GM + MP (12.5)
Relative kidney weight	0.50 ± 0.03	0.68 ± 0.04^##	0.62 ± 0.05	0.55 ± 0.04*	0.53 ± 0.03*	0.50 ± 0.07***
Serum creatinine (mg/dL)	0.78 ± 0.19	3.02 ± 0.48^##	3.02 ± 0.48	1.53 ± 0.42*	1.13 ± 0.29**	0.91 ± 0.07***
BUN (mg/dL)	24.90 ± 4.35	97.20 ± 4.40^###	95.22 ± 3.78	73.90 ± 6.55*	55.90 ± 12.7**	35.77 ± 9.42***
Creatinine clearance (mL/min)	16.80 ± 1.48	4.62 ± 0.85^###	6.01 ± 1.08	10.30 ± 0.84**	11.30 ± 1.22**	14.18 ± 1.65***

Data are expressed as mean ± SEM (n = 5) and analysed by one-way ANOVA followed by post-hoc Dunnett's tests. *p < 0.05, **p < 0.01, ***p < 0.001 as compared with GM-control group and ^##p < 0.01, ^###p < 0.001 as compared with normal group. BER: berberine; BUN: blood urea nitrogen; GM: gentamicin; MP: methylprednisolone.

Table 2. Effect of berberine on GM-induced alterations in oxido-nitrosative stress in rats.

Parameters	Normal	GM-control	GM + BER (10)	GM + BER (20)	GM + BER (40)	GM + MP (12.5)
SOD (U/mg of protein)	11.80 ± 1.16	7.46 ± 1.23#	8.12 ± 0.62	10.10 ± 0.78*	11.40 ± 0.54**	11.74 ± 0.43**
GSH (mg/mg protein)	45.00 ± 5.11	21.80 ± 2.50##	24.48 ± 1.88	29.90 ± 2.42*	40.40 ± 3.93**	44.22 ± 2.83**
MDA (nmol/l/mg ofprotein)	0.48 ± 0.13	2.49 ± 0.43##	2.27 ± 0.22	1.39 ± 0.44	0.76 ± 0.14**	0.51 ± 0.08***
NO (μg/mL)	108.51 ± 7.64	182.78 ± 16.60##	187.18 ± 10.78	190.01 ± 14.80	118.44 ± 10.60**	110.74 ± 17.21***

Data are expressed as mean ± SEM (n = 5) and analysed by one-way ANOVA followed by post-hoc Dunnett's tests. *p < 0.05, **p < 0.01, ***p < 0.001 as compared with GM-control group and #p < 0.01, ##p < 0.001 as compared with normal group. BER: berberine; BUN: blood urea nitrogen; GM: gentamicin; MP: methylprednisolone; SOD: superoxide dismutase; GSH: reduced glutathione; MDA: malonadehyde; NO: nitric oxide.

Figure 1. Effect of berberine on GM-induced alterations in renal mitochondrial enzyme activities in rats. Data are expressed as mean ± SEM (n = 5) and analyzed by one-way ANOVA followed by post-hoc Dunnett's tests. *p < 0.05, **p < 0.01, ***p < 0.001 as compared with GM-control group and ^###p < 0.001 as compared with normal group. BER: berberine; BUN: blood urea nitrogen; GM: gentamicin; MP: methylprednisolone.

Figure 2. Effect of berberine on GM-induced alterations in renal KIM-1, NGAL, NF-kB, and Bcl-2 mRNA expression in rats. Data are expressed as mean ± SEM (n = 5) and analyzed by one-way ANOVA followed by post-hoc Dunnett's tests. *p < 0.05, **p < 0.01, ***p < 0.001 as compared with GM-control group and ^###p < 0.001 as compared with normal group. BER: berberine; BUN: blood urea nitrogen; GM: gentamicin; MP: methylprednisolone.

Figure 3. Effect of berberine on GM-induced alterations in kidney histology in rats. Photomicrograph of sections of the kidney of normal (A), GM-control rats (B), methylprednisolone (12.5 mg/kg)-treated rats (C), berberine (20 mg/kg) treated rats (D), and berberine (40 mg/kg) treated rats (E). Necrosis (Yellow arrow), inflammatory infiltration (Green arrow) and increased thickness of basement membrane (Red arrow) H & E staining at 40× and 100 × (inset).

Table 3. Effect of berberine on GM-induced alterations in kidney histology in rats.

Parameters	Glomerular hypertrophy	Inflammatory infiltration	Congestion	Edema	Necrosis
Normal	0	0	0	0	0
GM-control	++++	+++	+++	+++	++++
GM + BER (20)	++++	++	+++	+++	+++
GM + BER (40)	++	++	+	++	++
GM + MP (12.5)	+	+	0	+	+

Note: 0: No abnormality detected.

+: damage/active changes up to less than 25%.

++: damage/active changes up to less than 50%.

+++: damage/active changes up to less than 75%.

++++: damage/active changes up to more than 75%.