Kidney injury and oxidative damage alleviation by Zingiber officinale: pharmacokinetics and protective approach in a combined murine model of osteoporosis

Abstract

Ginger (Zingiber officinale) is considered as a nutraceutical spice, which possesses several health promotion and benefits. This study was carried out to investigate the phyto-chemical composition, the antioxidant capacities, the drug-likeness, and pharmacokinetic properties of ginger extract on kidney injury-associated osteoporosis in rats. Phenolic and flavonoid contents were assessed by standard chemical analysis methods and HPLC. In vivo protective effect was based on the use of female rats to evaluate the effect on renal injury as a result of combined osteoporosis using biochemical markers, oxidative status, and histological analyses. Results showed that ZO contained appreciable amounts of phenolics and flavonoids and it exhibited high scavenging activity. Ovariectomy-associated corticotherapy induced severe renal injury marked by altered biochemical markers (creatinine, urea, and uric acid), reduced GFR, significative oxidative damage signs, and disrupted antioxidant status in the combined osteoporotic rats. The histopathological examination revealed structural modifications of kidney tissues. However, all these changes were reversed following the use of ZO. These results confirm the renoprotective and antioxidant potential of ginger against renal injuries in osteoporotic rats.

Keywords: Drug-likeness; Ginger; Histopathology; Kidney function; Pharmacokinetics.

Fig. 1

HPLC Chromatographic profiles of standard phenolic compounds and ZO extract. The peak numbers assigned to: (1) caffeic acid; (2) syringic acid; (3) ferulic acid; (4) rosmarinic acid; and (5) amentoflavone

Fig. 2

Bioavailability radars (A) and boiled-egg model (plot of WLOGP against TPSA, B) for the major ZO identified compounds. LIPO lipophilicity, SIZE Molecular size, POLAR Polarity, INSOLU Insolubility, INSATU Insaturation, FLEX Flexibility. The pink-colored area in the bioavailability radars corresponds to the most suitable zone for oral bioavailability. The white- and yellow-colored areas in the boiled-egg model correspond to the highest probability of GI absorption and BBB permeation according to the physico-chemical structures, respectively

Fig. 3

The effect of severe osteopenia and ginger on creatinine clearance and GFR in control (CTRL), combined model of osteoporosis (CMO) and osteoporotic treated rats with ZO (CMO + ZO) or with Clp (CMO + Clp). The data represent the mean ± SEM. Comparisons are made between two groups: Osteoporotic (CMO) versus control group (CTRL): ^*p < 0.05; ^**p < 0.01; Osteoporotic treated with ZO (CMO + ZO) or Clp (CMO + Clp) versus osteoporotic group (CMO): ^# p < 0.05; ^## p < 0.01

Fig. 4

The effect of severe osteopenia and ginger on renal protein and lipid peroxidation, superoxide dismutase, catalase and glutathione peroxidase activities and GSH content (AOPP, MDA, SOD, CAT, GPx, and GSH, respectively), in control (CTRL), combined model of osteoporosis (CMO) and osteoporotic treated rats with ZO (CMO + ZO) or with Clp (CMO + Clp). The data represent the mean ± SEM. Comparisons are made between two groups: Osteoporotic (CMO) versus control group (CTRL): *p < 0.05; **p < 0.01; Osteoporotic treated with ZO (CMO + ZO) or Clp (CMO + Clp) versus osteoporotic group (CMO): ^# p < 0.05; ^## p < 0.01

Fig. 5

Kidney histological photographs of rats stained with hematoxylin–eosin (HE) of controls and experimental groups. (A) CTRL rats showed normal appearance of kidney, normal glomeruli and tubules. (B and B’) CMO rats showed multiple foci of hemorrhage and necrosis. (C + D) Showed almost normal cellular architecture of the kidney in CMO + ZO and CMO + Clp rats, respectively. Original magnification × 400 (scale bar 0.1 mm). G glomerulus, DT distal tubule, PT proximal tubule, PG pseudo-lobulated glomerulus, SG shrinked glomerulus, ^#Necrotic debris in tubular lumen; *Necrosis; Arrows indicate: (filled circle) Bowman’s space (filled diamond) Leukocyte infiltration (right arrow) Hemorrhage