Additive effects of dietary glycotoxins and androgen excess on the kidney of a female rat model

Peer review under responsibility of Alexandria University Faculty of Medicine.

Available online 8 August 2015

Figures & data

Table 1 Serum parameters and AGEs IHC expression in the six studied groups. Values are presented as mean ± S.E. Bold cells denote statistically significant differences. ^§Derived from Mann–Whitney–Wilcoxon test for independent samples (level of statistical significance: 0.007, due to the Bonferroni correction); ^†derived from Kruskal–Wallis test (level of statistical significance: 0.05).

Parameters	Group A1 (mean ± SE)	Group A2 (mean ± SE)	P-value (A1 vs. A2 comparison)^§	Group B1 (mean ± SE)	Group B2 (mean ± SE)	P-value (B1 vs. B2 comparison)^§	Group C1 (mean ± SE)	Group C2 (mean ± SE)	P-value (C1 vs. C2 comparison)^§	p-value for overall between-groups heterogeneity^†
Body weight and serum parameters
Body weight at baseline (g)	99.7 ± 2.7	94.7 ± 2.6	0.200	190.5 ± 5.5	184.0 ± 8.2	0.470	197.0 ± 4.3	199.7 ± 4.2	0.851	0.0001
Body weight at 3 months (g)	253.7 ± 8.8	190.7 ± 7.9	0.0001	250.5 ± 11.9	218.5 ± 5.8	0.025	206.0 ± 4.5	193.3 ± 4.4	0.050	0.0001
AGEs (U/mL)	5.15 ± 0.2	7.19 ± 0.3	<0.0001	5.29 ± 0.24	8.91 ± 0.39	0.0002	4.48 ± 0.24	6.72 ± 0.26	<0.0001	0.0001
Testosterone (ng/mL)	5.41 ± 0.49	8.96 ± 0.68	0.0004	6.73 ± 0.44	16.27 ± 2.21	0.0002	4.39 ± 0.63	9.42 ± 0.98	<0.0001	0.0001
Insulin (μU/mL)	1.11 ± 0.08	2.33 ± 0.19	0.0001	1.16 ± 0.02	2.33 ± 0.36	0.069	1.22 ± 0.04	1.96 ± 0.14	<0.0001	0.0001
CRP (μg/mL)	225.5 ± 10.3	437.4 ± 16.3	<0.0001	444.1 ± 8.6	429.2 ± 15.5	0.597	176.3 ± 10.9	356.3 ± 11.1	<0.0001	0.0001
Serum glucose (mg/dL)	112.0 ± 7.4	91.0 ± 9.5	0.120	127.1 ± 8.3	122.7 ± 8.7	0.821	119.0 ± 7.9	112.2 ± 6.6	0.548	0.177
Creatinine (mg/dL)	0.60 ± 0.02	1.41 ± 0.13	<0.0001	0.62 ± 0.02	1.96 ± 0.18	0.0002	0.66 ± 0.02	0.64 ± 0.03	0.480	0.0001
Immunohistochemical results – AGEs immunostaining
Expression in epithelial cells of proximal convoluted tubules (H-score)	40.8 ± 37.5	82 ± 59.2	0.1578	75.5 ± 55.3	78 ± 58.5	0.9395	18 ± 21.7	91.4 ± 45.6	0.0055	0.0744
Expression in epithelial cells of collecting ducts and distal convoluted tubules (H-score)	12.5 ± 24	30 ± 38.4	0.1483	14 ± 25.5	25 ± 28.7	0.3118	10 ± 17.3	21.4 ± 16.7	0.0891	0.3397

Figure 1 Effect of HA-diet and androgen exposure on creatinine levels. The prepubertal androgenized rats (A2) and adult androgenized rats (B2) on a HA-diet, exhibit higher serum creatinine levels, than the respective groups of rats on a LA-diet (A1 and B1). The non-androgenized group does not present any statistically significant difference (C1 and C2).

Figure 2 Effect of androgen exposure on CRP levels. The adult androgenized animals (B1 and B2) exhibited higher CRP levels when they were compared with the age-matched adult non-androgenized animals (C1 and C2), either fed with HA- or LA-diet.

Figure 3 Expression of AGEs in epithelial cells of proximal convoluted tubules. The group of rats fed with HA-diet [(A2) represents the prepubertal androgenized rats, (B2) the androgenized rats and (C2) the adult non-androgenized rats, fed with HA-diet] [exhibit higher AGE immunoreactivity than the respective animals fed with LA-diet [(A1) represents the prepubertal androgenized rats, (B1) the adult androgenized rats and (C1) the adult non-androgenized rats, fed with LA-diet]. Magnification ×100.

Figure 4 Box plot illustrating the higher AGEs immunoreactivity in C2 group when compared to C1 group (p = 0.0055) in epithelial cells of proximal convoluted tubules.

Table 2 Detailed list of the a priori designed comparisons between the study groups pertaining to the effects of age at androgenization or androgenization per se. Bold cells denote statistically significant differences. ^§Derived from Mann–Whitney–Wilcoxon test for independent samples (Level of statistical significance: <0.007 due to the Bonferroni correction).

Table 3 Intercorrelations between study parameters. Spearman’s rho values with respective p-values in brackets are presented. Correlations with p-values < 0.05 have been highlighted in bold.