Protective effects of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice

Figures & data

Table 1. Effects of apigenin, myricetin or their combination on kidney function tests.

Parameters Drugs	Creatinine level (mg/dL)	BUN level (mg/dL)
Control	0.57 ± 0.016	25.5 ± 1.5
Apigenin	0.56 ± 0.32	25.25 ± 1.3
Myricetin	0.48 ± 0.02	22.5 ± 0.71
Apigenin + Myricetin	0.45 ± 0.03	21.37 ± 0.59
Cisplatin	1.6 ± 0.173*	58 ± 1.15*
Cisplatin + Apigenin	0.83 ± 0.03^a	41.7 ± 1.1^a
Cisplatin + Myricetin	0.77 ± 0.025^a	37.2 ± 2.08^a
Cisplatin + Apigenin + Myricetin	0.62 ± 0.02^a	29.6 ± 0.67^a,b,c

Figure 1. Effects of apigenin, myricetin or their combination on serum caspase-3 activity. Data were expressed as mean ± SEM (n = 6–8). *Significantly different from the normal control group at p < 0.05. ^aSignificantly different from cisplatin group at p < 0.05. ^bSignificantly different from apigenin group at p < 0.05. ^cSignificantly different from myricetin group at p < 0.05.

Figure 2. Effects of apigenin, myricetin or their combination on serum TNFα level. Data were expressed as mean ± SEM (n = 6–8). *Significantly different from the normal control group at p < 0.05. ^aSignificantly different from cisplatin group at p < 0.05. ^bSignificantly different from apigenin group at p < 0.05. ^cSignificantly different from myricetin group at p < 0.05.

Figure 3. Effects of apigenin, myricetin or their combination on serum IL-6 activity. Data were expressed as mean ± SEM (n = 6–8). *Significantly different from the normal control group at p < 0.05. ^aSignificantly different from cisplatin group at p < 0.05. ^bSignificantly different from apigenin group at p < 0.05. ^cSignificantly different from myricetin group at p < 0.05.

Figure 4. Effects of apigenin, myricetin or their combination on serum COXI level. Data were expressed as mean ± SEM (n = 6–8). *Significantly different from the normal control group at p < 0.05. ^aSignificantly different from cisplatin group at p < 0.05. ^bSignificantly different from apigenin group at p < 0.05. ^cSignificantly different from myricetin group at p < 0.05.

Figure 5. Effects of apigenin, myricetin or their combination on serum COXII level. Data were expressed as mean ± SEM (n = 6–8). *Significantly different from the normal control group at p < 0.05. ^aSignificantly different from cisplatin group at p < 0.05. ^bSignificantly different from apigenin group at p < 0.05. ^cSignificantly different from myricetin group at p < 0.05.

Table 2. Effects of apigenin, myricetin or their combination on serum oxidative stress biomarkers.

Parameters Drugs	Serum GSH Level (μmol/mL)	Serum MDA Level (n mol/mL)	Serum catalase Activity(U/mL)
Control	3.47 ± 0.14	10.48 ± 0.43	15.67 ± 0.309
Apigenin	3.2 ± 0.15	10.53 ± 0.44	15.36 ± 0.34
Myricetin	3.42 ± 0.12	8.92 ± 0.26	15.53 ± 0.37
Apigenin + Myricetin	3.89 ± 0.14	7.22 ± 0.18	16.22 ± 0.32
Cisplatin	0.91 ± 0.037*	25.3 ± 1.51*	4.23 ± 0.232*
Cisplatin + Apigenin	1.7 ± 0.09^a	17.8 ± 0.37^a	9.05 ± 0.29^a
Cisplatin + Myricetin	2.21 ± 0.16^a	14.3 ± 0.24^a	10.24 ± 0.39^a
Cisplatin + Apigenin + Myricetin	2.89 ± 0.78^a^,^b	11.28 ± 0.29^a^,^b^,^c	12.42 ± 0.34^a^,^b^,^c

Data were expressed as mean ± SEM (n = 6–8).

* Significantly different from the normal control group at p < 0.05.

^a Significantly different from cisplatin group at p < 0.05.

^b Significantly different from apigenin group at p < 0.05.

^c Significantly different from myricetin group at p < 0.05.

Figure 6. (A) Photomicrographs stained with hematoxylin and eosin from mice kidney sections of normal control, apigenin, myricetin and their combination. These sections showed normal renal histological picture. (B) Photomicrographs stained with hematoxylin and eosin from mice kidney sections of Cisplatin-treated group showing extensive tubular necrosis, tubular dilatation, vacuolization and cast formation. (C) Photomicrographs stained with hematoxylin and eosin from mice kidney sections of Cisplatin-treated groups with apigenin and myricetin displaying remarkable improvement in the histological appearance. (D) Photomicrographs stained with hematoxylin and eosin from mice kidney sections of Cisplatin-treated groups with apigenin and myricetin combination showing nearly normal histological appearance.