Nephroprotective effect of bee honey and royal jelly against subchronic cisplatin toxicity in rats

Abstract

Cisplatin is one of the most potent and effective chemotherapeutic agents. However, its antineoplastic use is limited due to its cumulative nephrotoxic side effects. Therefore, the present study was undertaken to examine the nephroprotective potential of dietary bee honey and royal jelly against subchronic cisplatin toxicity in rats. Male Wistar rats were randomly divided into controls, cisplatin-treated, bee honey-pretreated cisplatin-treated and royal jelly-pretreated cisplatin-treated groups. Bee honey and royal jelly were given orally at doses of 20 and 100 mg/kg, respectively. Subchronic toxicity was induced by cisplatin (1 mg/kg bw, ip), twice weekly for 10 weeks. Cisplatin treated animals revealed a significant increase in serum level of renal injury products (urea, creatinine and uric acid). Histopathologically, cisplatin produced pronounced tubulointerstitial injuries, upregulated the fibrogenic factors, α-smooth muscle actin (α-SMA) and transforming growth factor β1(TGF-β1), and downregulated the cell proliferation marker, bromodeoxyuridine (Brdu). Dietary bee honey and royal jelly normalized the elevated serum renal injury product biomarkers, improved the histopathologic changes, reduced the expression of α-SMA and TGF-β1 and increased the expression of Brdu. Therefore, it could be concluded that bee honey, and royal jelly could be used as dietary preventive natural products against subchronic cisplatin-induced renal injury.

Keywords: Cisplatin; Honey; Nephrotoxicity; Rat; Royal jelly.

Fig. 1

Histopathologic section stained with H&E, ×100, a control untreated kidney showing normal renal architecture. b Markedly dilated tubules in rats treated with ciplatin only and inflammatory cells along with fibrosis expanded in the interstitial tissue. c Minimal histopathologic changes are seen in honey treated rats. d Some tubules are moderately ectatic, RJ group

Fig. 2

Immunohistochemical staining of α-SMA, ×100. a Control untreated kidney showing normal expression of SMA within the wall of interstitial arterioles. b Cisplatin treated rat showing a moderate reaction in the interstitial tissue. c Honey treated rats expressing no reactivity. d RJ treated rats expressing minimal reaction. e Data represent the expression level of α-SMA in cisplatin, honey, and RJ groups: *significant difference from normal control group at P < 0.05, **significant difference from cisplatin group at P < 0.05

Fig. 3

Immunohistochemical staining of TGF-β-1, ×100. a Control untreated kidney showing minimal expression of TGF within the renal tubular epithelial cells. b Cisplatin treated rat showing many positive epithelial cells in the renal tubules. c Honey treated rats revealing low reactivity. d RJ treated rats showing reduced reaction. e Data represent the expression level of TGF-β-1 in cisplatin, honey, and RJ groups: *significant difference from normal control group at P < 0.05, **significant difference from cisplatin group at P < 0.05

Fig. 4

Immunohistochemical staining of BrdU, ×100. a Control untreated kidney showing minimal expression of BrdU within the renal tubular epithelial cells. b Few epithelia cells showing a weak reaction in the cispaltin group. c The honey group has many positive epithelial cells. d In the RJ treated group epithelial cells reacting to BrdU are seen at moderate numbers of renal tubules. e Data represent the expression level of BrdU in cisplatin, honey, and RJ groups: *significant difference from normal control group at P < 0.05, **significant difference from cisplatin group at P < 0.05