Evaluation of effects of melatonin and caffeic acid phenethyl ester on acute potassium dichromate toxicity and genotoxicity in rats

Abstract

Objective: The aim of this study is to investigate the possible protective effects of melatonin and caffeic acid phenethyl ester (CAPE) on potassium dichromate (K₂ Cr₂O₇)-induced nephrotoxicity and genotoxicity.

Methods: A total of 40 Wistar albino rats were divided into five groups: control, K₂Cr₂O₇(K₂Cr₂O₇15 mg/kg, one dose, i.p.), K₂Cr₂O₇ + melatonin, K₂Cr₂O₇ + CAPE, and K₂Cr₂O₇ + melatonin + CAPE. Urine and blood samples were collected from rats before scarification. One kidney was collected for histopathological studies, and the other was stored at -80°C for further determination of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione S-transferase (GST), and glutathione reductase (GR) levels with spectrophotometric method. Comet assay was used to evaluate the genotoxicity.

Results: We observed a significant amelioration in genotoxicity by melatonin and simultaneous melatonin + CAPE treatment compared to K₂Cr₂O₇ group (p₁, p₂< 0.05). SOD, CAT, GSH, GST, and MDA levels did not change when compared with controls. When K₂Cr₂O₇ applied group was treated with melatonin and CAPE, neither melatonin nor CAPE made any changes in kidney GSH, GST, SOD, and MDA levels (P > 0.05). We noted that treatment with CAPE and melatonin + CAPE together caused a significant decrease in renal tissue damage, an upregulation in the kidney CAT levels (P < 0.05) and a slight healing at GR levels when compared with the K₂Cr₂O₇ group.

Conclusion: Our results revealed, CAPE and melatonin may have protective effects on K₂Cr₂O₇ induced nephrotoxicity and cellular damage in rats.

Keywords: Caffeic acid phenethyl ester; melatonin; nephrotoxicity; oxidative stress; potassium dichromate.

Figure 1

Semi-quantitative analysis of renal injury in different treatment groupsComet assay. Control group (a). Potassium dichromate group (b). Melatonin-treated potassium dichromate group (c), caffeic acid phenethyl ester-treated potassium dichromate group (d), melatonin and caffeic acid phenethyl ester treated potassium dichromate group (e)

Figure 2

H and E, staining of kidney sections. In the control group, normal histological appearance of renal cortex, glomerulus, and tubular epithelial cells (a). In the potassium dichromate, group glomeruli appear normal, damage to tubular epithelial cells (→) and presence of hyaline casts in the tubular lumen (b). In the melatonin-treated potassium dichromate group (c) and caffeic acid phenethyl ester-treated potassium dichromate (d), the presence of hyaline casts in tubular lumen. Glomeruli appear normal. Melatonin and caffeic acid phenethyl ester treated potassium dichromate group, the generally intact tubular epithelial cells and a cast free tubular lumen. Glomeruli appear normal (e) (p: Proximal tubule, d: Distal tubule, g: Glomeruli, hc: Hyaline cast [Bar 20 μm])